Contemporary

Endodontics
for Children and
Adolescents

Anna B. Fuks
Moti Moskovitz
Nili Tickotsky
Editors

123
Contemporary Endodontics for Children
and Adolescents
Anna B. Fuks • Moti Moskovitz
Nili Tickotsky
Editors

Contemporary
Endodontics for Children
and Adolescents
Editors
Anna B. Fuks Moti Moskovitz
Department of Pediatric Dentistry Faculty of Dental Medicine
Hadassah Medical Center Hebrew University of Jerusalem
Faculty of Dental Medicine Jerusalem, Israel
Hebrew University of Jerusalem
Jerusalem, Israel

Nili Tickotsky
The Goodman Faculty of Life Sciences
Bar Ilan University
Ramat Gan, Israel

ISBN 978-3-031-23979-3    ISBN 978-3-031-23980-9 (eBook)

https://doi.org/10.1007/978-3-031-23980-9

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Preface

As the corresponding editor of the Pediatric Endodontics book, which was an excel-
lent seller and was even translated into two languages, one of them Chinese, I was
asked by the Springer representative if I would consider editing a second edition. As
many new techniques and materials have been developed in the last five years, and
due to issues not related to this book a second edition was impossible, we decided
to publish a new, up-to-date book with a broader spectrum. I felt this was a big
enterprise to undertake by myself, so I invited two experienced colleagues, Prof.
Moti Moskovitz and Dr. Nili Tickotsky, to join me as co-editors of the new book.
The chapters were all written by highly qualified experts.
The book we present here describes pulp therapy for children and adolescents
from a holistic approach that highlights the new developments in the field. It has two
parts: the first updates the readers on the biological aspects of pulp therapy, and the
second deals with a wide range of clinical aspects.
In the first part, we describe the formation, structure, and function of the dental
pulp as revealed by the latest single-cell visualization technologies. We then thor-
oughly discuss carious lesions and their impact on the pulp.
The second part examines the clinical considerations in the decision to perform
pulp treatment. We emphasize the need to integrate pupal diagnostics with patient-­
dependent factors such as behavior management and pulpal pain mechanisms. This
part of the book includes comprehensive descriptions of current treatments for each
type of caries-inflicted tooth damage, from selective caries removal through direct
pulp capping, pulpotomy, pulpectomy and root canal therapy for the primary denti-
tion to direct pulp capping, and endodontic treatment of young permanent teeth. We
describe both traditional and new pulp treatment materials and the techniques and
materials used to restore both primary and young permanent teeth and summarize
innovative biological approaches for pulp regeneration such as the use of stem cells.
We hope that both dentists and students will benefit from the expertise and
knowledge this book contains and from the holistic approach it advocates.

Jerusalem, Israel Anna B. Fuks

Jerusalem, Israel  Moti Moskovitz
Ramat Gan, Israel  Nili Tickotsky

v
Contents

1 Introduction: Pulp Therapy for Children

and Adolescents – Historical Approach, Present
Perspective, and Future Directions����������������������������������������������������������   1
Anna B. Fuks, Moti Moskovitz, and Nili Tickotsky
2 Cellular and Molecular Mechanisms Guiding the
Development and Repair of the Dentin–Pulp Complex ������������������������   9
Tal Burstyn-Cohen
3 
Dental Pain, Mechanism of Action ���������������������������������������������������������� 23
Yaron Haviv, Shirley Leibovitz, and Yair Sharav
4 
Assessment and Management of Pain in Pediatric Dentistry���������������� 31
Diana Ram and Esti Davidovich
5 
Behavioral Approaches as an Adjunct for Pulp Therapy���������������������� 41
Janice A. Townsend and Ari Kupietzky
6 The Caries Lesion: Diagnosis, Decision-­Making,
and Recommendations for Lesion Management������������������������������������ 55
Fernando Borba de Araujo, Marisa Maltz,
Cleber Paradzinski Cavalheiro, and Tathiane Larissa Lenzi
7 
Pulp Response to Clinical Procedures and Dental Materials���������������� 73
Josimeri Hebling, Igor Paulino Mendes-Soares,
Rafael Antonio de Oliveira Ribeiro,
and Carlos Alberto de Souza Costa
8 
SDF as an Adjunct Approach for the Management of Caries �������������� 97
Yasmi O. Crystal and Sasan Rabieh
9 
Guidance to Achieve Clinical Pulpal Diagnosis and Operative
Decisions������������������������������������������������������������������������������������������������������ 111
Marcio Guelmann and Roberta Pileggi
10 
Management of Deep Dentin Carious Lesions: A Contemporary
Approach for Primary and Young Permanent Teeth������������������������������ 127
Marisa Maltz, Luana Severo Alves, Fernando Borba de Araújo,
and Anna B. Fuks
vii
viii Contents

11 
Bioactive Ceramics for Pediatric Dentistry �������������������������������������������� 149
Carolyn Primus
12 Primary and Permanent Teeth Treated with Direct
Pulp Capping���������������������������������������������������������������������������������������������� 187
James A. Coll
13 
Pulpotomy for Primary Teeth: Techniques and Materials�������������������� 201
Yasmi O. Crystal and Anna B. Fuks
14 
Non-Vital Pulp Therapies in Primary Teeth�������������������������������������������� 223
Moti Moskovitz and Nili Tickotsky
15 Sealing and Building Up the Pulp Chamber and Crown
with Glass Ionomer and Other Materials After Pulp Therapy ������������ 249
Joel H. Berg
16 
Restorative Guidelines for Endodontically Treated Primary Teeth������ 259
E. LaRee Johnson and Marcio Guelmann
17 Endodontic Treatment for Young Permanent Teeth ������������������������������ 281
Eyal Nuni and Iris Slutzky-Goldberg
18 
Restoring the Endodontically Treated Young Permanent Tooth ���������� 323
Zafer C. Çehreli
19 
Elucidating Tooth Development and Pulp Biology by Single-Cell
Sequencing Technology������������������������������������������������������������������������������ 333
Jimmy K. Hu and Amnon Sharir
20 Biological Basis for Repair and Regeneration in Modern
Endodontics and New Treatment Considerations���������������������������������� 353
Carolina Cucco and Jacques E. Nör
Introduction: Pulp Therapy for Children
and Adolescents – Historical Approach, 1
Present Perspective, and Future
Directions

Anna B. Fuks, Moti Moskovitz, and Nili Tickotsky

Contents
1.1 Introduction 1
1.2 Historical Perspective: Personal Approach 3
1.3 Present Perspectives 4
1.4 New Developments and Future Directions 6
References 6

1.1 Introduction

Pediatric dentistry evolved from an extraction-oriented approach, where primary

teeth with inflamed pulps were mainly extracted, with no attempt to preserve the
tooth and the pulp, to a specialty emphasizing prevention of oral and dental dis-
eases [1].
Historically, pediatric dentistry was based on three pillars:

1. Stopping the progression of early childhood caries (ECC) by implementing res-

torations, pulp therapy, and extractions.

A. B. Fuks (*) · M. Moskovitz

Department of Pediatric Dentistry, Hadassah Medical Center, Faculty of Dental Medicine,
Hebrew University of Jerusalem, Jerusalem, Israel
e-mail: [email protected]; [email protected]
N. Tickotsky
The Goodman Faculty of Life Sciences, Bar Ilan University, Ramat Gan, Israel

© The Author(s), under exclusive license to Springer Nature Switzerland AG 2023 1

A. B. Fuks et al. (eds.), Contemporary Endodontics for Children and
Adolescents, https://doi.org/10.1007/978-3-031-23980-9_1
2 A. B. Fuks et al.

2. Establish prevention regimes to stop the recurrence of the disease.

3. Develop regular care protocols to ensure good oral health through adulthood [2].

The preventive tools in pediatric dentistry had remained the same for years and
included a four-part manifest that advocated drinking fluoridated water, brushing
teeth with fluoridated paste, eating a low-sugar diet, and visiting a dentist twice a year.
In the last few years, preventive measures have been based on the child’s and
family’s caries risk assessment (CRA), leading to a more promising and useful
chairside diagnosis that emphasizes individualized patient-centered care [2].
With the improvement in diagnostic criteria and the appearance in the market of
new dental products and materials, better and more conservative approaches have
been developed, including esthetic and sophisticated restorative techniques that are
part of contemporary pediatric dentistry [3].
However, social changes are occurring at an extremely rapid pace, and it is
imperative to accommodate them with new information. Children are changing, and
so are their parents and dentists. A new generation of young pediatric dentists may
not accept the traditional methods to manage and treat their patients while dealing
with their accompanying parents.
The current tendency is to avoid using aversive techniques, which were tradi-
tionally employed by pediatric dentists in the past. Consequently, there is an
increased use of deep sedation and general anesthesia for the dental treatment of
children [4].
In 2017, the US Food and Drug Administration published a warning that general
anesthesia in children less than 3 years of age should be avoided, as it may affect
their neurological development. This observation led several European and South
American pediatric dentists to start using less invasive restorative techniques for
young uncooperative children. Presently, the use of conservative techniques such as
ART (atraumatic restorative technique), silver diamine fluoride (SDF), and the Hall
technique, as a temporary or definitive treatment is increasing worldwide [5].
The conservative approach goes further regarding pulp therapy. It has been estab-
lished long ago that the human dental pulp has a remarkable potential for self-­
healing when encountering severe damage, particularly in young patients, mainly
due to the high degree of cellularity and vascularity. In addition, pediatric endodon-
tics, which treats the pulp of primary and young permanent teeth, has its consider-
ations and characteristics and must always be considered in the context of both the
dentition and the patient.
This book has two main purposes: the first is to emphasize the changes leading
to the conservative approach to restorative and endodontic techniques, and the sec-
ond is to discuss the various clinical treatment techniques for primary and young
permanent teeth.
1 Introduction: Pulp Therapy for Children and Adolescents – Historical Approach… 3

1.2 Historical Perspective: Personal Approach

The first mention of capping an exposed pulp with gold foil was described by Philip
Pfaff, a dentist at the court of the Prussian king Frederick II, in Berlin in 1756. At
that time, the current belief was that the pulp must be irritated by cauterization in
order to heal and several materials were used empirically. At the beginning of the
twentieth century, it became obvious that microorganisms were the main reason for
pulp inflammation. More attention was paid to finding effective disinfecting agents,
some of which were very cytotoxic [1].
The difficulties in achieving accurate diagnoses led to a deficient assessment of
pulp status that in turn led to the selection of incorrect treatments. In fact, necrotic
pulps were sometimes capped [3]. Hermann studied the reaction of vital tissue to
calcium hydroxide in root canal fillings between 1928 and 1930 and proved it was a
biocompatible material [1].
As one of the few remaining members of the first generation of pediatric dentists
and the senior editor of this book (ABF), I felt it would be interesting to comment
on the changes I have experienced during my teaching and clinical career in pedo-
dontics, later named pediatric dentistry.
As a young practicing dentist who did not have enough theoretical and practical
experience in behavior management of children, I was more afraid to administer a
local anesthetic on a child than the child was afraid of “getting a shot.” So, when I
needed to treat a tooth with a deep cavity and expected low compliance, I would use
a devitalization paste before performing a pulpotomy. The devitalizing agent, in
addition to causing intense pain, when improperly placed into the cavity, could
cause gingival inflammation and even bone necrosis. I was aware that the use of this
approach is empirical and has no scientific background, so I searched for relevant
literature and was surprised to find a university-based paper from 2017 discussing
the advantages and disadvantages of available methods for the treatment of pulpitis,
including mortal endodontic treatment!!! [6]
As a resident at the Children’s Hospital at the University of Alabama, I had
encountered different clinical problems and had to find a way to solve them; this is
how my interest in histology and pulp therapy evolved.
In the early seventies, already teaching clinical pediatric dentistry at the
Department of Pedodontics of the Hadassah School of Dental Medicine in Israel,
where I still belong as professor emeritus, I would write in a treatment plan “pos-
sibility of a pulpotomy” if deep caries were disclosed in the middle third of the
cavity in the preoperative radiograph. This approach was not accepted in some uni-
versities, and the argument was that even in shallow proximal cavities or middle-­
third occlusal cavities, the pulp was inflamed and had to be treated by pulpotomy.
Some serious discussions developed among pediatric dentists on this subject, and
many didn’t accept the concept that pulp inflammation was reversible if the tooth
was properly restored without marginal leakage.
4 A. B. Fuks et al.

Controversies existed also regarding materials for pulpotomy: calcium hydrox-

ide was initially recommended as the material of choice for primary teeth pulpoto-
mies. However, as many cases of internal root resorption were observed after
calcium hydroxide pulpotomies, formocresol became the preferred pulpotomy
dressing material worldwide, and calcium hydroxide continued to be used mainly in
the Scandinavian countries.
Several materials have been proposed to replace formocresol for pulpotomies in
primary teeth, and nowadays, bioactive bioceramic materials are preferred, in cases
where more conservative treatment was not possible.
Two treatments that have been established in the last years are indirect and direct
pulp treatments, both of which were historically unacceptable for primary teeth.
Indirect pulp was recommended only for deep cavities in young permanent teeth,
preferably in a two-stage technique.
I am pleased to have survived and continued in pediatric dentistry to see the
development of a biological and conservative approach to treatment and for being
able to publish this book with the help of the most prominent members of dentistry
and biology.

1.3 Present Perspectives

This book aims to familiarize dental students as well as general practitioners and
pediatric dentists with the different modalities of pulp therapy for children and ado-
lescents from a holistic approach that highlights the new developments in the field.
It has two parts: the first updates the readers on the biological aspects of pulp ther-
apy, and the second deals with a wide range of clinical aspects.
Chapter 2 provides a synopsis of the development of the dentin-pulp complex,
highlighting its importance, as well as key features of the ectomesenchyme in the
development and maintaining healthy teeth. Recent advances and new insights into
the biology of the dentin-pulp complex and how they may be exploited to improve
dental treatment are highlighted.
Chapter 3 defines dental pain as pain associated with sensory activation of the
dentin, whereas pulpal pain is usually associated with an inflammatory reaction of
the pulp tissues.
In Chapter 4, the use of local anesthesia is elaborated on, stressing the virtually
pain-free treatment and explaining the association with anxious thoughts and mis-
conceptions in young patients.
Chapter 5 stresses that pulp therapy procedures in children and adolescents pres-
ent dentists with unique challenges, due to the increase of preexisting pain and the
complexity of the procedures. For many, the appointment and treatment will be a
first-time dental experience. Success is contingent on parental guidance and basic
behavior management techniques that promote relaxation and pain control. For chil-
dren with previous negative experiences, reframing techniques can reestablish a
positive dental attitude.
1 Introduction: Pulp Therapy for Children and Adolescents – Historical Approach… 5

Chapter 6 is a brief overview on caries development and control strategies as

well as achieving an accurate diagnosis. This chapter discusses and summarizes the
recommendation for the management of initial, moderate, and extensive caries
lesions, reaching the outer half of dentin in primary and young permanent teeth.
Chapter 7 provides the readers with reliable, evidence-based data obtained from
laboratory studies and clinical trials performed in the last decades in different fields
of dentistry related to dental materials, as well as pulp biology and regeneration.
Chapter 8 centers on silver diamine fluoride (SDF) that combines the antibacte-
rial actions of silver with the re-mineralizing effects of fluoride. The combined alka-
line stabilizing solution creates a synergistic effect that slows collagen degradation
in dentin. Even with the dark staining that characterizes treated lesions, it is an
invaluable tool for caries management, especially when traditional restorative care
is not a viable first line of treatment.
Chapter 9 explains how determining the accurate status of the pulp of primary
and young permanent teeth is a challenging task for any provider treating children
and young adults. The younger the child is, the more difficult it is to obtain objective
and clear information, since children are considered “poor historians.” The goal of
this chapter is to provide the clinician with knowledge of currently available tests
and evidence-based recommendations, to achieve pulpal diagnosis.
Chapter 10 is a brief overview of caries lesion development and pulp reactions as
well as the relationship between the bacterial invasion of dental tissues and the pos-
sibility of lesion control. This chapter brings together the existing evidence on con-
servative treatment, aiming to preserve both tooth vitality and structure. It also
summarizes the contemporary approach to the management of deep dentin carious
lesions.
Chapter 11 describes bioactive ceramic cements. These types of cement are set
with water and have become the standard of care in vital pulp therapy for primary
teeth. These bioceramic dental materials are dimensionally stable, strong, and insol-
uble and so are suitable for pediatric indication, from pulp capping to apexification.
Over the past 25 years, they improved enormously in clinical convenience, and the
price has diminished.
Chapter 12 focuses on direct pulp capping (DPC) for primary and permanent
teeth; it reviews the biological properties of materials used for DPC and factors to
be considered before performing DPC. There is now evidence-based dentistry
(EBD) research showing that DPC is successful for vital primary and permanent
teeth but conflicting evidence on permanent teeth diagnosed as having irreversible
pulpitis. Evidence-based dentistry literature is reviewed as well as the techniques
for DPC treatment methods.
Chapter 13 discusses pulpotomy, a technique for vital pulp therapy that has been
used for decades. The success of this technique varies with the material used as the
pulpotomy agent, and all materials used in the last century have both advantages
and disadvantages. In the last two decades, the introduction of bioactive calcium
silicate cements like MTA and Biodentine has changed the stage, allowing better
sealing of the remaining pulp tissue.
6 A. B. Fuks et al.

Chapter 14 elaborates on pulpectomy, a root canal procedure for primary teeth

that is indicated when the radicular pulp exhibits clinical signs of irreversible pulpi-
tis or pulp necrosis, while the roots show minimum or no resorption. This chapter
elaborates on the clinical steps of the technique-sensitive pulpectomy treatment,
reviews new concepts and technologies, and describes the materials and instruments
that are used.
Chapter 15 talks about the use of glass ionomer and other restorative materials.
An ideal material should restore the integrity of the tooth structure and the arch, seal
the cavity from the oral environment, and prevent recurrent lesions and the spread
of infection into the dental pulp. When deep carious lesions are in close proximity
to the pulp and extended to multiple surfaces, full coronal coverage is
recommended.
Chapter 16 discusses the restoration of the pulp-treated tooth after the comple-
tion of the pulp therapy. The types of restorations and their materials are discussed
as well as the techniques and tips for using these materials. The chapter aims to
provide the clinician with step-by-step guidance as well as options for restorations
of pulp in primary teeth.
Chapter 17 discusses endodontic treatment of young permanent immature teeth
that differs from that of mature permanent teeth due to their high potential healing
properties. The procedure is expected to promote healing and preserve the vitality
of the tooth. When other treatment options fail, root canal treatment is carried out.
Distinct problems in disinfection and obturation make the treatment very challeng-
ing and may also necessitate apexification.
Chapter 18 discusses a variety of post-endodontic treatment options in young
anterior and posterior permanent teeth, as well as factors related with long-term suc-
cess. Endodontically treated young permanent teeth with reduced structural integ-
rity usually require large restorations, which can be challenging for pediatric
dentists, due to limited evidence and the lack of an acknowledged standard of care.

1.4 New Developments and Future Directions

Chapter 19 deals with new insights gained by single-cell technologies and focuses
on developmental aspects.
Chapter 20 describes the efforts to exploit the regenerative capacity of stem cells
in the dental pulp and novel therapeutic approaches that aim to achieve complete
regeneration of dental tissues. The authors review fundamental mechanisms of pulp
repair and regeneration and discuss novel stem cell-based strategies for dental pulp
tissue engineering.

References
1. Fuks AB, Peres B. Pediatric endodontics: past and present perspectives and future directions
1–5, 51–70, 103–116. Switzerland: Springer International Publishing; 2016.
1 Introduction: Pulp Therapy for Children and Adolescents – Historical Approach… 7

2. Casamassimo PS, Townsend JA. In: Novak AJ, et al., editors. The importance of pediatric
dentistry in pediatric dentistry infancy through adolescence. 6th ed. Amsterdam: Elsevier
Inc.; 2019.
3. Dammaschke T. The history of direct pulp capping. J Hist Dent. 2008;56(1):9–23.
4. Kupietzky A. Wright’s behavior Management in Dentistry for children. 3rd ed. New York:
Wiley Blackwell; 2022.
5. Innes NP, Steward M. The Hall technique, a simplified method for plating stainless steel
crowns of primary molars, may be as successful as traditionally placed crowns. J Evid Based
Dent Pract. 2015;15(2):70–2.
6. Antoniak M, Gabiek K, Onopiuk B, Dabrowska E. Selected aspects of treatment of irreversible
pulpitis. Prog Health Sci. 2017;7(2):111–6.
Cellular and Molecular Mechanisms
Guiding the Development and Repair 2
of the Dentin–Pulp Complex

Tal Burstyn-Cohen

Contents
2.1 Introduction 9
2.2 Formation of the Dentin–Pulp Complex 10
2.3 Mesenchymal Condensation and Key Features of the Early Dental Papilla 12
2.4 Odontoblast Differentiation 14
2.5 Dentin Regeneration and Repair 16
2.6 The Role of Inflammation in Dentin Biology 19
2.7 Concluding Remarks 20
References 20

2.1 Introduction

Although dentin and pulp of mature teeth differ in composition and physical proper-
ties, they share the same developmental origin and constitute a single functional
unit. Odontoblasts—the dentin-forming cells—reside within the pulp throughout
the lifetime of the tooth, and mesenchymal stem cells within the pulp can differenti-
ate into dentin-laying odontoblasts. Thus, resident cells of the pulp, including
immune and pulp stem cells as well as odontoblasts, contribute to dentin repair in
adult tissue. Understanding the molecular cues and biological mechanisms that
guide development of the dentin-pulp unit and lead to odontoblast differentiation
with productive dentin formation may contribute to develop restorative treatments.
This chapter will provide an overview of the development of the dentin-pulp

T. Burstyn-Cohen (*)
Institute for Biomedical and Oral Research, Faculty of Dental Medicine, The Hebrew
University, Jerusalem, Israel
e-mail: [email protected]

© The Author(s), under exclusive license to Springer Nature Switzerland AG 2023 9

A. B. Fuks et al. (eds.), Contemporary Endodontics for Children and
Adolescents, https://doi.org/10.1007/978-3-031-23980-9_2
10 T. Burstyn-Cohen

complex and introduce selected recent advances in understanding the molecular and
cellular mechanisms of dentin-pulp development and how they may be harnessed
into regenerative dentistry.

2.2 Formation of the Dentin–Pulp Complex

During early embryogenesis, cranial neural crest cells (NCCs) of neuroepithelial

origin delaminate and detach from the neural ectoderm, as they undergo an
epithelial-to-­mesenchymal transition. Their new mesenchymal properties, deriving
from ectodermal origin, have gained them a unique name: ectomesenchyme. Neural
crest-derived ectomesenchymal cells are important contributors to head and neck
development, including dentition. The epithelial-to-mesenchymal transition (EMT)
is crucial for tooth development, as ectomesenchymal cells that colonize the man-
dibular and maxillary arches of the first pharyngeal arch are the progenitors of den-
tin and pulp. Ectomesenchymal cells undergo morphological and molecular
changes, also acquiring a robust migratory potential. As they migrate and populate
the pharyngeal arches, ectomesenchymal cells proliferate and differentiate as they
respond to local signals within their migratory path. Responding to molecular cues
emanating from the adjacent oral ectoderm induces morphological modulations,
which are followed by molecular and functional changes transforming NCCs into
dental papilla. The dental papilla will further differentiate and give rise to the tooth
pulp and surrounding mineralized dentin (Fig. 2.1). With only a basement mem-
brane separating the dental papilla from the overlying ectoderm, both tissues remain
in close, physical contact. Successful reciprocal epithelial-mesenchymal interac-
tions between the oral ectoderm and dental papilla layers will provide signals neces-
sary for the coordinated development of these two embryonic layers into mature
dental tissues including the pulp, dentin, and enamel (Fig. 2.1).
These reciprocal epithelial-mesenchymal signals instruct molecular and cellular
changes, which drive dental development. This process is recognized through a
series of morphological changes, which have been classically described as the den-
tal lamina, bud, cap, and the early and late bell stages of tooth development
(Fig. 2.1). Another, more recent classification that emphasizes functionality has
been used to describe odontogenesis in four phases: initiation, morphogenesis, cell
differentiation (cytodifferentiation), and matrix apposition. During initiation, the
oral ectoderm slightly thickens at the prospective tooth sites, thereby defining the
dental ectoderm, which marks the location of the future corresponding tooth, still
within the continuum of the developing mandibular and maxillary arches. At the
dental lamina stage, ectodermal cells within these future dental regions undergo
rapid and asymmetric proliferation, resulting in their invagination into the underly-
ing ectomesenchyme, defined morphologically as the tooth bud. The invaginating
dental lamina cells signal to the adjacent ectomesenchymal cells, which respond in
aggregation, and signal back to the dental lamina, which expand to form a three-­
dimensional cap over the aggregated ectomesenchyme, morphologically recognized
as the cap stage. During the cap stage, first signs of histodifferentiation are observed,
2 Cellular and Molecular Mechanisms Guiding the Development and Repair… 11

Dental lamina Bud stage Cap stage Bell stage Erupted tooth

Initiation Morphogenesis Histo-differentiation

Fig. 2.1 Stages of tooth development.

Oral ectoderm (pink) and neural crest-derived ectomesenchyme (ochre) in the first pharyngeal
arch. During the initiation phase, ectoderm thickening marks the site of tooth development. The
ectoderm then grows into the ectomesenchymal layer, forming a bud-like structure. The underlying
ectomesoderm reacts by cellular condensation (depicted by brown dots) underneath the invaginat-
ing ectoderm. The enamel knot (light blue) develops in the center of the bud within the ectodermal
tissue and is normally histologically visible at the cap stage. The enamel knot inhibits local ecto-
dermal growth but promotes the growth and elongation of ectodermal tissue located further radi-
ally, which results in a bell-shaped tooth bud. The growing front of the ectodermal layer closes on
the underlying ectomesoderm, defining the dental papilla (dotted area), which will give rise to
odontoblasts and the vital pulp tissue of mature dentition. Cells located at the border of both tissues
begin to differentiate: ameloblasts from the inner enamel epithelium (IEE) and odontoblasts from
the dental papilla. First signs of mineralization are seen at the bell stage. Finally, in the mature
erupted tooth, enamel (white) is the external mineralized tissue, deposited by ameloblasts, which
have died and disappeared. Dentin tissue (grey) is formed, surrounding the pulp (red), and is main-
tained by odontoblasts, which reside within the dental pulp. The gingival tissue (pink) covers and
supports the base of the tooth. Dental pulp cells have the capacity to differentiate into odontoblasts
and form new dentin. The corresponding functional stages of initiation, morphogenesis, and
cyto(histo)-differentiation are aligned below. See text for more details

as the cap forms distinct layers. The innermost layer overlays and defines the under-
lying ectomesenchyme as the dental papilla together with its ensheathing dental
follicle, which will contribute to the support tissues of the tooth, mainly cementum
and periodontal ligament (PDL). The innermost layer of the cap has now differenti-
ated into the inner enamel epithelium (IEE) and develops a vital signaling center
marking the beginning of crown formation known as the enamel knot. Complex
signaling pathways within and between the enamel knot and the dental papilla as
well as the IEE cells guide cusp formation and hence influence crown morphology.
These will be described later in this chapter. Recent research has identified the mor-
phogen Sonic Hedgehog (Shh) as a negative regulator of cusp formation [1]. Time
lapse imaging of developing tooth buds labeled with fluorescent cell cycle reporters
elegantly demonstrates the complex coordination of cellular dynamics and prolif-
eration, which drive tooth formation [2].
Whereas proliferation continues in areas distant from the enamel knot, signals
emanating from this organizational center inhibit proliferation of enamel knot and
adjacent cells, thereby allowing proliferation of peripheral cells, which transforms
12 T. Burstyn-Cohen

the cap-shaped tooth bud into an elongated structure, which appears histologically
as a bell (Fig. 2.1). It is during the bell stage that IEE and dental papilla cells ter-
minally differentiate into ameloblasts and odontoblasts, respectively, secreting ini-
tial mineralized tissue. This is known functionally as the matrix apposition stage.
Development and differentiation of both the dental papilla and the prospective
enamel continue in a developmental gradient, as the differentiation wave advances
to form the full crown of the tooth. Since the onset of root development does not
begin until tooth eruption, there is a delay in the development of radicular pulp and
the accompanying PDL and cementum. Despite this delay, which may be quite
significant (up to 10–15 years for molars), the pulp tissue in mature teeth appears
uniform and continuous at the transition between crown and radicular pulp. The
subsequent paragraphs will chronologically describe key aspects in pulp
development.

2.3 Mesenchymal Condensation and Key Features

of the Early Dental Papilla

The first histological evidence marking the future dental papilla within the ectomes-
enchyme is the cellular condensation, which occurs just under the dental ectoderm.
Numerous cellular and molecular mechanisms may lead to cellular condensation. In
the mouse an increase in ectomesenchymal cell proliferation localized to the future
dental papilla was observed as early as the initiation phase [3]. This increase in
ectomesenchymal cell proliferation overlaps with a dynamic co-expression of syn-
decan and tenascin, which concurs transiently with condensation, as observed in
molar teeth of mice. Tenascin and syndecan interact with extracellular membrane
proteins and growth factors, which led the authors to propose these proteins regulate
local cell-cell interactions, inducing proliferation and thus contributing to local con-
densation [3]. More recently, a mechano-chemical mechanism was proposed to con-
tribute to mesenchymal condensation [4]. According to the mechano-chemical
mechanism, Fgf8 and Sema3f are produced by the dental ectoderm but act differen-
tially on mesenchymal cells. Secreted Fgf8 accumulates at the basement membrane
and acts as a morphogen to attract dental papilla cells. Concurrently, the repulsive
protein Sema3f is secreted and accumulates at the basement membrane but is later
released and acts as a repulsive morphogen. As a result, Fgf8 attracts mesenchymal
cells, while Sema3f repels them, resulting in opposing forces being exerted on these
cells, leading to their localized condensation. Moreover, mesenchymal cells that
underwent tight condensation upregulated the odontogenic transcription factors
Pax9, Msx1, Lhx8, as well as BMP4, whereas loosely packed cells did not. These
findings identify cell compaction as a mechano-physical mechanism that upregu-
lates odontogenic gene expression within the emerging dental papilla [4]. Additional
molecules including transcription factors, morphogens, and cell matrix and mem-
brane proteins have been linked to mesenchymal condensation in tooth develop-
ment and are mentioned in [5].
2 Cellular and Molecular Mechanisms Guiding the Development and Repair… 13

At the same time, still within the bud stage, the dental mesenchyme acquires an
inductive role, which now drives odontogenesis. This was elegantly demonstrated by
Kollar and Biard using heterotypic grafting experiments. When bud-stage dental
papilla was co-cultured with ectopic ectodermal tissue isolated from the foot or snout,
these heterotypic grafts developed into tooth structures, indicating the molecular driv-
ing force for tooth development now resides within the dental mesenchyme [6].
At the cap stage, histodifferentiation occurs within epithelial cells, which turn
into the enamel organ. The enamel organ consists of four distinct cell populations:
the inner and outer enamel epithelium (IEE, OEE, respectively), the cervical loop
(CL), and the stellate reticulum (SR). IEE cells will further differentiate into amelo-
blasts; the CL cells are stem cell-like cells which will drive root development. The
SR and the OEE are transient populations, which provide nutrition and protection to
the developing tooth germ. The primary enamel knot (EK) develops at the center of
the enamel organ just above the IEE layer and may be considered a fifth cell popula-
tion due to its distinct cellular organization and key function as a signaling center,
which is crucial for shaping the developing tooth. These cell populations develop in
defined areas within the tooth bud. The IEE cells are situated immediately adjacent
to the underlying dental papilla with which they are known to molecularly interact.
The basement membrane (BM) and extracellular matrix separating the dental epi-
thelium and dental papilla allow for accumulation of signaling molecules necessary
for the epithelial-mesenchymal cross talk instructing tooth development. The BM
will later disintegrate and mark the location of the future dentin-enamel junction.
Thus, tooth bud development is driven by the cross talk between epithelium and
ectomesenchyme cells, both tissues acquiring a positional molecular profile and
cellular organization, which is postulated to support tooth development. Across the
BM, on the mesenchymal side, papilla cells that are located just beneath the IEE
will differentiate into odontoblasts, whereas remaining cells will differentiate into
other pulp cell populations (see below). Thus, at the cap stage, dental epithelium,
papilla, and follicle are clearly distinguished in histological preparations by their
morphology and organization, and it is thought that this positional information of
both ectodermal and mesenchymal cells is necessary for tooth development. A
recent study by Hu et al. has revealed a surprising degree of plasticity within these
cells [7]. Dental mesenchyme and epithelium of developing tooth buds at the cap
stage were dissected, isolated, and dissociated into single-cell epithelial and mesen-
chymal suspensions. When these single-cell suspensions were re-associated in vitro,
teeth developed. These teeth displayed a characteristic morphology and cellular
organization, with differentiated and functional odontoblast and ameloblasts [7],
demonstrating the remarkable plasticity of both dental epithelium and papilla at this
stage. The ability of both cell types to reorganize and fully reconstruct a tooth bud
with a complete and functional enamel organ indicates that despite losing their posi-
tional information, epithelial cells have not yet committed to the IEE, OEE, CL, and
SR and that mesenchymal cells can still become either papilla or follicle cells.
Overall, this and other such experiments suggest that plasticity in situ may be
greater than currently appreciated [7–9]. It would be interesting to harness newly
14 T. Burstyn-Cohen

developed techniques such as spatial transcriptomics and single-cell RNA sequenc-

ing combined with pseudo time analysis to understand the molecular changes that
accompany such cellular reorganizations and underpin tooth development.
It is the dental papilla at this developmental phase that dictates tooth shape and
identity. This was shown by Kollar and Biard when molar dental papilla and dental
epithelium were isolated at early cap stages from either molar or incisor teeth. The
tissues were left intact but recombined such that one tissue was from a molar tooth
and the other from an incisor. When papilla and epithelium were taken from tooth
germs of the same developmental age (synchronic), the reconstructed tooth shape
always matched the original identity of the dental papilla [10]. However, when het-
erochronic (papilla and epithelium from different developmental ages) reconstruc-
tions were made, the instructive potential of the papilla over the epithelium was
blurred, with the highest tooth identity (molar versus incisor) attributed to embry-
onic day 13 papilla, corresponding to the cap stage. These experiments, also sup-
ported by additional reconstitution experiments using tissues at different
developmental time points and from various locations, indicate that within intact
tissues at the cap stage, tooth identity is already determined and that this informa-
tion is encoded within the dental papilla to form the pulp, cementum, PDL, and
alveolar bone, whereas dental ectoderm still exhibits morphogenic plasticity [5,
6, 9–11].

2.4 Odontoblast Differentiation

The majority of the knowledge pertaining to tooth development comes from studies
in mice, although single-cell technologies are currently being developed and used to
understand both murine and human tooth development. For more on this, the reader
is referred to a dedicated chapter on new technologies (See Chap. 19). During the late
cap and early bell stages, dental pulp cells residing just under the basement mem-
brane of the dental ectoderm respond to secreted ectodermal signals, which stimulate
dental papilla cells to differentiate into pre-odontoblasts and finally into odonto-
blasts. Thus, it seems that spatial distribution of dental papilla cells at a certain devel-
opmental time point, rather than a predetermined fate program, dictates odontoblast
fate. This conclusion is also supported by the dissociation experiments described
above [7, 9–11]. The molecular reciprocal cross talk between dental epithelium and
mesenchyme provides a mechanism, which secures the coordinated development of
dental papilla and ectoderm-derived dental tissues, especially toward the deposition
of pre-dentin and enamel matrix, which will begin at the late bell stage.
Studies by Ruch et al. that were focused on examining the cell cycle of dental
papilla cells showed that dental papilla and pre-odontoblasts undergo about 14–15
2 Cellular and Molecular Mechanisms Guiding the Development and Repair… 15

mitotic divisions before they become post-mitotic odontoblasts. Lengthening of the

cell cycle was recorded as development proceeds from the dental lamina stage to the
first post-mitotic odontoblasts [12]. The basement membrane may play an impor-
tant role in accumulation of numerous extracellular matrix proteins such as fibro-
nectin, tenascin, laminin, hyaluronic acid, and collagens, which may regulate
odontoblast differentiation [13]. As pre-odontoblasts develop and approach their
terminal differentiation, their mitotic spindle becomes perpendicular to the base-
ment membrane, such that one daughter cell will acquire the position immediately
adjacent to the BM and the other daughter cell will be located one cell width below,
facing the dental papilla. Only the cells in contact with the BM further undergo
terminal differentiation, which is accompanied by cellular elongation, and redistri-
bution of cellular organelles [12, 13]. Terminally differentiated odontoblasts form a
terminal web composed of collagen type I and III fibers (von Korff fibers), fibronec-
tin, cytoplasmic filaments, and tight junctions, which function as a barrier sealing
off the secretory apical end of the odontoblast from the basal end and the dental
papilla. This terminal web barrier therefore allows for directional secretion, accu-
mulation, and mineralization of pre-dentin without being diluted by dental papilla
components [13]. The BM degrades as pre-dentin and enamel matrix are secreted.
The dentin layer thickens in a process termed appositional growth as odontoblasts
secrete newly formed pre-dentin, and the pre-dentin secreted at earlier time points
fully mineralizes into dentin. As a result, odontoblasts are pushed and crowded due
to the forming crown concave curvature into the dental pulp. Mature odontoblasts
may remain viable for decades; however, their secretory capacity decreases. The
initial “mantle” dentin secreted is less organized as odontoblast still undergo matu-
ration and their secretory organelles mature, allowing for continuous and organized
apposition of pre-dentin, which mineralizes into primary dentin. Secondary dentin
apposition is slower and initiates with root formation. The transition between pri-
mary and secondary dentinogenesis is also reflected by odontoblast morphology,
specifically the reduction in the secretory machinery by autophagy, reduction in cell
size, and overall flattening, which has been described for human-aged odonto-
blasts [14].
Terminal differentiation of odontoblasts is also regulated by the IEE and the BM,
which serves as a matrix onto which numerous cell adhesion and extracellular
matrix signaling proteins (such as fibronectin, tenascin, laminin, and chondroitin
sulphate) and growth factors (IGF-1, BMPs and TGFβ proteins) accumulate [13].
Differentiating radicular odontoblasts can be detected in human teeth during root
elongation. The morphological differences between mature pulp and the still devel-
oping dental papilla are also visible in an incisor tooth that had erupted but is still
growing its root (Fig. 2.2).
16 T. Burstyn-Cohen

a b c

Fig. 2.2 Pulp and dental papilla in a developing tooth.

(a) A longitudinal view of the apical aspect of an incisor tooth extracted from a 2-year-old patient.
The root is still growing, radicular dentin is indicated. While the pulp toward the crown (to the left)
is fully developed with visible vasculature, the apical aspect of the root is still developing. Fully
differentiated dentin-producing odontoblasts reside in the pulp periphery (black asterisks). The
dental papilla cells are located at the apical aspect of the tooth, to the right (boxed area). The boxed
area is magnified in B.
(b) The apical, developing aspect of the root. This region still contains undifferentiated dental
papilla cells. The area marked by the rectangle is magnified in C.
(c) New dentin deposited by young odontoblasts (white asterisks) near the cervical loop. The den-
tal papilla cells undergoing odontoblast differentiation are located more centrally (white arrows).
Hematoxylin and Eosin staining. These images are courtesy of Prof. Anna Fuks

2.5 Dentin Regeneration and Repair

Primary and secondary dentin are physiological dentins, as they are naturally
formed throughout the life of the vital tooth. Primary dentin is formed prior to tooth
eruption, while secondary dentin deposition commences after tooth eruption. Adult
teeth have the capacity to regenerate dentin and form tertiary dentin in response to
injury, disease, or other physiological insult. Tertiary dentin is deposited in response
to a range of stimuli and reflects the important role of the dentin-pulp complex as
the first line of defense against pathogens, including cariogenic bacteria that have
entered dentin tissue (illustrated in Figs. 2.3 and 2.4).
The different types of injury and impact on the tooth instigate distinct reparative
processes. In case of a relatively subtle stimuli such as shallow dentin caries, gentle
trauma, or operative procedure, reactionary dentin is formed by the viable odonto-
blasts, which deposit pre-dentin. Such dentin appears rather similar in structure to
the physiological dentin, featuring relatively organized dentinal tubuli, which are
often continuous to those in the physiological dentin (Fig. 2.5). Sub-odontoblastic
Hoëhl cells present in the subodontoblastic layer may also differentiate into odonto-
blasts to secrete pre-dentin. However, when odontoblasts are more massively
affected by severe trauma, invasive carious lesions, or noxious agents, mesenchy-
mal stem cells are recruited from the deeper layers of the pulp and differentiate into
odontoblasts in response to odontogenic cues. Such reparative dentin is formed at
higher pace and is characteristically disorganized [13, 15].
2 Cellular and Molecular Mechanisms Guiding the Development and Repair… 17

Fig. 2.3 Occlusal view

into decaying dentin.
A clinical image before
root canal obturation. The
infected pulp has been
removed, exposing carious
dentin (gray area). View
through an access hole that
has been made in the
crown enamel. This image
is courtesy of Dr. Sharonit
Sahar-Helft

a b

c d

Fig. 2.4 The ultrastructure of dentin as visualized by scanning electron microscopy (SEM).
(a) SEM micrograph of a specimen showing healthy dentin with open dentinal tubuli. The globular
structures represent a globular (calcospherie) mineralization of dentin.
(b) In this specimen, most dentinal tubuli are open; some are sclerotic. Sclerotic tubuli may indi-
cate the odontoblasts processes that reside within the tubuli and maintain them have died.
(c) Dentin with a bacterial biofilm. Bacteria appear as small round balls, and the dentinal tubuli
have been covered by the bacterial biofilm.
(d) A larger view into a dentinal tubuli with several bacteria on the dentin surface. This image is
courtesy of Dr. Sharonit Sahar-Helft
18 T. Burstyn-Cohen

Fig. 2.5 Reactionary dentin.

Reactionary (tertiary, 3°) dentin is produced in reaction to mild trauma or stimuli and is confined
to the affected area. Physiological (secondary, 2°) dentin is located more peripherally. The white
arrow points to the line separating secondary and tertiary dentin. Dentinal tubuli appear as orga-
nized parallel white lines in the physiological dentin and are less organized in the reactionary
dentin. The odontoblasts that have produced the reactionary dentin are marked by yellow asterisks.
Some artifacts in preparation are seen as white regions devoid of organic matter. Hematoxylin and
Eosin staining. This image is courtesy of Prof. Anna Fuks

Much research is focused on revealing and understanding the molecules and

mechanisms, which drive pulp stem cells to differentiate into odontoblasts, as this
would potentially allow the exploitation of the pulp stem cell pool for regenerative
purposes in restoration of dental pulp or dentin and beyond. Indeed, pulp regenera-
tive therapies were previously reported for single-rooted teeth and recently for
multi-rooted teeth [16].
Understanding the molecular pathways leading to odontogenesis and dentino-
genesis would advance the development of therapeutic dentin restoration. Neves
et al. recently reported successful dentine formation and restoration following
manipulation of the Wnt signaling pathway [17]. In a mouse molar tooth damage
model involving pulp exposure, delivery of the small molecule inhibitor for
Glycogen synthase kinase-3 (GSK-3) activated Wnt signaling within the dental
pulp, which promoted the formation of reparative-like dentin [17]. Further investi-
gations into how to best mimic and promote the natural process of reparative dentin
formation are expected to contribute to dentin restoration and protection of injured
or inflamed pulp.
Insights into human odontoblast differentiation are mostly gained by ex vivo
experimentation, allowing for structural, molecular, biochemical, and gene expres-
sion analysis. For example, third molar human dental pulp cells from 14 to 16-year-­
old donors were isolated and differentiated ex vivo into odontoblast-like polarized
cells, which presented with many known in vivo odontoblastic cellular and morpho-
logical features. Differentiated odontoblast-like cells contained secretory vesicles,
presented with odontoblastic processes, generated gap and desmosome-like
2 Cellular and Molecular Mechanisms Guiding the Development and Repair… 19

junctions, and secreted dense bundles of extracellular matrix and collagens.

Moreover, needle like crystals with the composition and structure of hydroxyapatite
(HAP) were observed, as well as transcripts encoding the dentin matrix protein
DSPP [18].
Given that dental pulp stem cells share many similarities with mesenchymal
stem cells from other locations, including bone marrow mesenchymal stem cells
[19], their full therapeutic potential is yet to be discovered. Molecules of prominent
morphogen and growth factor signaling pathways play a role in the maintenance of
pulp stem cells and their differentiation to functional odontoblasts. Members of the
BMP (Bone Morphogenetic Proteins), Wnt (Wingless and Int-1), and Shh (Sonic
Hedgehog) pathways have been identified to regulate dental stem cell biology [15,
18–21]. IGF (insulin growth factor)-1 and IGF-2, FGFs (fibroblast growth factor),
PDGF (platelet-derived growth factor), VEGF (vascular endothelial growth factor)
have all been implicated in these processes [12, 13, 21, 22]. Some of these mole-
cules are constituents of the dentin, embedded within the dentin matrix during den-
tinogenesis and may be released or exposed upon tooth decay or insult [23]. Immune
and inflammatory events were also shown to be upregulated and participate in the
complex processes, leading to odontoblast differentiation and dentin repair,
described below.

2.6 The Role of Inflammation in Dentin Biology

Because regenerative dentin is produced in response to injury or infectious stimuli,

the immune system is also activated. Similar to other body tissues, sentinel immune
cells reside within the pulp under steady-state conditions and are important for
effective immune surveillance and for maintaining tissue homeostasis, including the
regulation of cell proliferation and removal of apoptotic cells [24, 25].
Numerous pulp cells participate in the inflammatory response by secreting cyto-
kines or otherwise responding to danger signals upon injury [13, 15, 21, 26]. These
cytokines not only recruit immune cells as part of an inflammatory process but also
signal onto dental pulp stem cells and odontoblasts, which express cytokine recep-
tors [25, 27–30]. Neves et al. have recently reported that upon injury to dentin, pulp-­
resident macrophages accumulate at the injury site and remain [31]. Moreover,
ablation of macrophages delayed Wnt-induced modulation of pulp stem cells and
their engagement in reparative dentin formation [31].
However, lessons from numerous inflammatory models have shown that control-
ling the magnitude and duration of inflammation is crucial for tipping between a
potentially destructive or reparative environment [32]. This is also true for inflam-
mation within the dentin-pulp complex, reviewed in [33]. Regulated inflammation
serves as a defense mechanism against infection and injury and supports tissue
repair, while chronic or acute inflammation may promote disease. A recent tran-
scriptomic study revealed the heterogeneity of immune cells present in the pulp of
both mouse and human pulp [34] and bacterial components are also recognized by
other cells of the pulp including fibroblasts and stem cells [35, 36] in addition to
odontoblasts, as mentioned above.
20 T. Burstyn-Cohen

2.7 Concluding Remarks

This chapter highlighted the basic cellular and molecular mechanisms guiding the
development of the dentin-pulp complex. Significant dentinogenesis takes place
postnatally, but all forms of dentinogenesis are essentially a developmental process.
The challenges aiming at controlling dentin repair for better oral and tooth health
rely on understanding the molecular mechanisms as well as the numerous cell types
involved and how to harness their complex biology to improve dental treatment.

Acknowledgments I would like to thank Prof. Anna Fuks and Dr. Sharonit Sahar-Helft for fruit-
ful and critical discussions and for their generosity in sharing images. This book chapter has been
made possible thanks to support from the Israel Science Foundation (ISF grant 655/18).

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Dental Pain, Mechanism of Action
3
Yaron Haviv, Shirley Leibovitz, and Yair Sharav

Contents
3.1 Dentinal Pain 24
3.2 Pulpal Pain 25
References 27

Pain according to the recent definition of the IASP (International Association for the
Study of Pain) is “an unpleasant sensory and emotional experience associated with, or
resembling that associated with, actual or potential tissue damage” [1]. It can be acute or
chronic and contains a complex orchestra of physiological and psychological mechanisms.
Dental pain is a very common type of pain. The term dental pain refers to den-
tinal pain associated with sensory activation of the dentine and pulpal pain associ-
ated usually with inflammatory reaction of the pulp tissue.
Dentinal pain, derived from stimulation of the dentine, has unique features; any
sensory stimulation, such as mechanical, thermal, or chemical, results in pain. No
sensations such as touch, cold, or warm are reported under these stimulations.
Furthermore, the mechanisms of dentinal pain conduction are not explained by
direct nerve conduction for reasons discussed below. Dentinal pain results from
exposure of the dental tissue usually by carious lesions or due to trauma. Pain
derived from the pulp is unique in the sense that the pulp tissue is confined by dental
hard tissue that does not allow for inflammatory tissue swelling or expansion,

Y. Haviv (*) · Y. Sharav

Department of Oral Medicine, Sedation & Maxillofacial Imaging, Faculty of Dental
Medicine, Hadassah Medical Center, Hebrew University of Jerusalem, Jerusalem, Israel
e-mail: [email protected]; [email protected]
S. Leibovitz
Department of Pediatric Dentistry, Barzilai Medical Center, Ashkelon, Israel

© The Author(s), under exclusive license to Springer Nature Switzerland AG 2023 23

A. B. Fuks et al. (eds.), Contemporary Endodontics for Children and
Adolescents, https://doi.org/10.1007/978-3-031-23980-9_3
24 Y. Haviv et al.

resulting in excruciating pain. Pulp inflammation is usually the result of infection

mostly by carious lesions invading the pulp or occasionally due to migraine-like
neurovascular central mechanisms. We also refer to a pre-pain phenomenon, another
feature of dental pain.

3.1 Dentinal Pain

Dentin hypersensitivity is one of the most common complaints of patients in the

dental clinic [2]. There have been many reviews regarding the mechanisms of sen-
sitivity and/or pain in the dentine of mammalian teeth [3–8]. A recent narrative
review relates to some of the recent research that expanded our knowledge and pos-
sible new theories for dentinal sensitivity. It suggests a relation among odontoblasts
and dental afferent neurons that takes place by the release of several mediators,
which are involved on the transduction of dentinal pain (Fig. 3.1) [9].
When examining how far nerve fibers originating in the pulp extend into the
dentine, microscopic analyses revealed that the nerves reach about half as far as the
odontoblastic processes, and never get all the way to the dentino-enamel junction

Fig. 3.1 The cross talk between odontoblasts and axons may take place by the release of media-
tors. About 10% of the dental pulp afferent neurons express TRPV1, which was upregulated by
caries and caries by-products. These results suggest that odontoblasts and dental afferent neurons
are involved in the transduction of dentinal pain (Aminoshariae and Kulild 2021, by permis-
sion) [9]
3 Dental Pain, Mechanism of Action 25

[5, 10]. It has been suggested that the odontoblast itself may be able to act as a
receptor for sensory input within the dentine [11]. A study based on immunohisto-
chemistry showed the presence of the Transient Receptor Potential Vanilloid
Subfamily Member 1 (TRPV1) channel on odontoblast membranes, suggesting that
these cells can respond to heat or other noxious stimuli [12].
Furthermore, the evidence of gap junctions between neurons and odontoblasts is
inconclusive [13, 14].
When studying dentinal pain, experiments have shown that stimuli such as dry-
ing with absorbent paper or blowing air, physical trauma (e.g., cutting, scratching,
probing), and changes in osmotic pressure, temperature, or pH cause pain. On the
other hand, placement of known algesic solutions (which cause pain when applied
to the base of a skin blister [15]), e.g., potassium chloride, acetylcholine,
5-­hydroxytryptamine (5-HT), bradykinin, and histamine, on exposed dentine did
not cause pain [4, 16]. The lack of nerves within the dentine and the absence of pain
following the application of neuroactive chemicals led to alternative hypotheses
about the mechanisms of dentinal pain, including the hydrodynamic theory by
Brannstrom [17]. Brannstrom proposed that the movement of fluid within the den-
tinal tubules is able to alter the structure of nociceptive fibers in the pulp, thereby
activating mechanoreceptors and causing the transmission of a pain signal. Evidence
supports Brannstrom’s hypothesis, whereas other proposals, e.g., the neural theory
and odontoblastic transduction theory, have not been substantiated yet [14]. By
behaving as a passive hydraulic connection between the stimulated area and
pressure-­sensitive neuronal terminals in the pulp, the dentinal tubules transfer the
signal of the existence of a noxious stimulus. These pressure-sensitive nerve cells
have group A fibers that are much more sensitive to outward fluid flow than inward
flow in the dentinal tubules [18]. The hydrodynamic theory was supported by find-
ings suggesting the involvement of the transient receptor potential (TRP) channel
family, a class of mechanosensitive ion channels expressed in the sensory system of
the teeth [19, 20]. An extensive review by Magloire et al. discusses facts and hypoth-
eses associated with dental pain and the odontoblasts [7].
Thus, for example, while the hydrodynamic theory still keeps valid, there are
some concerns regarding the low threshold stimuli producing dentinal pain. This
problem is addressed by Fried et al. [21], suggesting that pain is activated by low-­
threshold mechanoreceptors having pain-provoking CNS connectivity. Dental pain,
including dentinal but more specifically pulpal pain, was discussed in a recent arti-
cle referring to the new International Classification of Orofacial Pain (ICOP) and is
of benefit for both clinicians and researchers [22].

3.2 Pulpal Pain

The overriding consensus is that pain in the pulp is related to inflammation and its
mediators including cholinergic and adrenergic neurotransmitters, prostaglandins,
and cyclic adenosine monophosphate (cAMP) [23, 24]. Molecules such as prosta-
glandins (especially PGE2), bradykinin, and serotonin are able to activate neurons
26 Y. Haviv et al.

in the pulp. A study on bovine teeth showed that bradykinin-evoked calcitonin gene-­
related peptide (CGRP) release is increased by PGE2 [25]. A recent study demon-
strated upregulation of Toll-like Receptor 2 in dental primary afferents following
pulp injury [26]. Neurogenic inflammation occurs when trigeminal afferents are
stimulated antidromically and release vasoactive neuropeptides, including CGRP,
which play a central role in the initiation of neurovascular type headaches [27].
Analysis of human dental pulp revealed significantly greater expression of CGRP,
SP, and VIP, in permanent teeth relative to deciduous counterparts [28, 29].
This may explain the lack of children in reports of neurovascular vascular orofa-
cial pain (NVOP), a pulpal neurogenic inflammatory response in reaction to a
migraine-like antidromic activation [30, 31]. The onset and regulation of neuro-
genic inflammation in the pulp are thought to be related to bradykinin released dur-
ing inflammation. Furthermore, as caries progresses, there are significant elevations
in the neuropeptide Substance P (SP) integral to nociception. Interestingly, speci-
mens from painful teeth had higher levels of SP than those from asymptomatic teeth
[32]. SP affects the microvasculature both directly and indirectly, by interacting
with smooth muscle cells and causing histamine release, respectively, and alters its
permeability. Edema formation (modulated by nitric oxide [33]) and the ensuing
extravasation of plasma proteins are caused by SP and are essential to its pro-­
inflammatory effects [34] [35]. The altered pulpal vasculature lowers oxygen ten-
sion and the impaired microcirculation, together with the inflammation, increase the
intra-pulpal pressure. The pressure changes are uniquely painful in the teeth because
the nerve tissue is surrounded by dental hard tissues [36]. Higher levels of endo-
toxin were found in teeth with exudation, whereas elevated levels of PGE2 were
detected in teeth sensitive to percussion and palpation [37]. The expression levels of
tumor necrosis factor alpha (TNF alpha) in teeth with irreversible pulpitis correlate
with the severity of pain [38]. Glutamate receptors and vesicular glutamate trans-
porters (VGLUT) found in both the pulp and trigeminal ganglion support the notion
that a distinct glutamate signaling mechanism is involved in dental pain transmis-
sion and processing [39]. While it is clear that inflammation is involved in pulpal
pain, the interaction of its mediators and specific nerve fibers in the pulp is still
being investigated. In contrast to the C-fibers, pulpal A-fibers seem to be unaffected
by most inflammatory mediators [6]. However, leukotriene B4 (LTB4), a hyperalge-
sic factor with prolonged effects, sensitizes A-delta fibers [40]. Studies have shown
that C-type nociceptors are essential to the transmission of pain signals from
inflamed pulp tissue [24]. Interestingly, the pulp may be able to detect sensations
that are not painful, in particular following electric stimulation, [41] and the trans-
mission of these sensations may be via specific afferent nerves [42]. Based on
results of experiments using non-painful temporal and spatial summation, it seems
that “pre-pain” and painful sensations caused by electrical stimulation are evoked
by A-fibers [43, 44]. The hypothesis that there are two discrete types of afferent
nerves in the pulp is supported by Narhi et al. They noted that many of the myelin-
ated fibers in the pulp are of the A-β type, which may be responsible for the pre-pain
sensation evoked by electrical stimulation [18]. An interesting observation is that
teeth with open apices are frequently unresponsive to electric stimulation [45].
3 Dental Pain, Mechanism of Action 27

Considering that neuronal tissue is present at the time of eruption [46] and that mas-
seteric reflex activity occurs when these teeth are electrically stimulated [45], it
seems that segmental reflex connections are established prior to full functionality of
the cortical sensory projections [45].
Alterations in the trigeminal nuclei are among the physiological and chemical
central nervous system reactions to inflammation of the pulp. The changes have
been recorded in: mechanoreceptive fields; the response properties as well as
NMDA receptor mechanisms [47–50]. This chapter focuses on the mechanisms of
dentinal and pulpal pain; however, this is only the first step in the pain journey from
teeth to the cortex. Briefly, the sensory innervation of the teeth arises through the
mandibular and maxillary branches of the fifth trigeminal cranial nerve to the gas-
serian ganglion and from there through the subnucleus caudalis of the trigeminal
nucleus located in in the midbrain, through the ventral trigeminothalamic tract to
the thalamus and finally to the cortex [51].
Pain expression stems from a complex interaction of many variables, resulting in
an unpleasant sensory and emotional experience and not just a result of a noxious
stimulus. Pain management is therefore associated with removing the cause of the
noxious stimulus as well as alleviating fear and anxiety and addressing the personal
characteristics of each patient.

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Assessment and Management of Pain
in Pediatric Dentistry 4
Diana Ram and Esti Davidovich

Contents
4.1  ocal Anesthesia in Pediatric Dentistry
L 32
4.2 Topical Anesthesia 32
4.3 Needle Selection 33
4.4 Injection Rate 34
4.5 Techniques of Local Anesthesia 34
4.6 Conventional Local Anesthesia 34
4.6.1 Supraperiosteal Technique: Local Infiltration 34
4.6.2 Palatal tissue’s Anesthesia: Papillary-Interdental Anesthesia 34
4.7 Inferior Alveolar Nerve Block (IANB) 35
4.8 Computer-Controlled Local Anesthetic Delivery 36
4.9 Behavior Management During Local Anesthesia 36
4.10 Materials and Solutions 37
4.11 Side Effects and Complications 38
4.12 Toxicity 38
4.13 Allergy 38
4.14 Trauma to Soft Tissue 39
References 39

D. Ram (*) · E. Davidovich

Department of Pediatric Dentistry, Faculty of Dental Medicine, The Hebrew University of
Jerusalem and Hadassah, Jerusalem, Israel
e-mail: [email protected]; [email protected]

© The Author(s), under exclusive license to Springer Nature Switzerland AG 2023 31

A. B. Fuks et al. (eds.), Contemporary Endodontics for Children and
Adolescents, https://doi.org/10.1007/978-3-031-23980-9_4
32 D. Ram and E. Davidovich

4.1 Local Anesthesia in Pediatric Dentistry

Pain control is a central aspect of children’s cooperation during dental treatment and
is thus a particularly important component of pediatric dentistry. Fear-related behav-
ior has long been recognized as the most difficult aspect of patient management and
can be a barrier to good care.
Children who experience early painful procedures are likely to avoid dental treat-
ment throughout their lives. The most common sources of dental fear are the fear of
pain and fear of “the needle” and “the injection.”
Local anesthesia enables virtually pain-free treatment yet is associated with anx-
ious thoughts and misconceptions in young patients. Administering local anesthetic
injection may provoke anxiety not only in patients but also in dentists. In a survey
study, dentists reported a high level of stress when delivering local anesthesia to
anxious children, regardless of the responders’ years of experience, whether they
were pediatric dentistry specialists, their age, or sex [1].
The ideal anesthetic technique includes a painless procedure, either during the
delivery of the local anesthesia or during the operative procedure. According to
Klingberg et al., current evidence is insufficient in support of any pharmacologic
agent or injection technique as being superior to others [2].

4.2 Topical Anesthesia

The goal for topical anesthesia is to blunt the effect of the administration of local
anesthesia. Topical anesthesia minimizes painful stimuli or dulls the effect of the
procedure. A painful stimulus can be either the penetration of the needle or the
delivery of the local anesthetic solution. A topical anesthetic reduces the discomfort
that may be associated with insertion of the needle before injection of the local
anesthetic.
Topical anesthesia can be administered as gels, cream, ointment, liquid, sprays,
or lotions. Benzocaine, which is one of the most common topical anesthetics, can be
purchased over the counter or with prescription [3].
The mucosa at the site of the intended needle insertion should be dried, and a
small amount of topical anesthetic agent is then applied to the tissue with a cotton
swab. The effect is achieved within about 30 s, although keeping it in the place for
2–3 min may provide the best results [4].
If dental treatment is needed in a child under the age of 2, topical anesthesia
should be avoided due to the risk of developing benzocaine-induced methemoglo-
binemia (BIM) [5].
4 Assessment and Management of Pain in Pediatric Dentistry 33

4.3 Needle Selection

Needle selection should allow profound local anesthesia and adequate aspiration.
Needle gauges range from size 23 to 30. Needles with lower-gauge numbers have
larger inner diameters and provide less deflection as the needle passes through soft
tissues and more reliable aspiration. The depth of insertion varies not only by injec-
tion technique but also by the age and size of the patient. Dental needles are avail-
able in three lengths: long (32 millimeters [mm]), short (20 mm), and ultrashort
(10 mm). Most needle fractures occur during the administration of inferior alveolar
nerve blocks with 30-gauge needles. A needle can break upon insertion to the hub,
when the needle is weakened due to its bending before insertion into the soft tissues,
or by patient movement after the insertion [6].
A short (20 mm) or a long (32 mm), 30- or 27-gauge needle may be used for
most intraoral injections in children, including mandibular blocks (Fig. 4.1).
According to Kupietzky and Schwartz [7], short needles should be used for all
techniques (excluding intraligamentary injections), regardless of age and the type of
injection.

Long: 27 gauge Mandibular block

Short: 30 gauge- 21 mm Buccal infiltration

Short: 27 gauge- 21 mm Buccal infiltration

Short: 30 gauge- 19 mm Buccal infiltration

Extra-short: 30 gauge- 12 mm - intraligamentary

- infiltration anterior teeth

Fig. 4.1 Needles

34 D. Ram and E. Davidovich

4.4 Injection Rate

There is no consensus regarding the optimal rate of delivery of local anesthesia, but
most authors and clinical practice guidelines have recommended a slow rate.
According to Melamed, slow injection is defined ideally as the deposition of 1 mL
of local anesthetic solution in not less than 60 s. Therefore, a full 1.8-mL cartridge
requires about 2 min to be deposited [8]. However, Kupietzky et al. do not recom-
mend a prolonged injection procedure [7]. The authors of this chapter support
Melamed’s recommendation as a means of reducing pain.

4.5 Techniques of Local Anesthesia

The most common techniques for local anesthesia in children are conventional
injections and computerized local anesthesia.

4.6 Conventional Local Anesthesia

4.6.1 Supraperiosteal Technique: Local Infiltration

This technique is indicated for anesthetizing maxillary teeth (primary and perma-
nent) and mandibular anterior teeth. The use of this technique for mandibular molars
is controversial. According to Oulis et al. and Sharaf et al. [9, 10], infiltration of
primary mandibular teeth is appropriate for restorative treatment but does not pro-
vide sufficient anesthesia for pulp treatment and extractions. The recommended
needles for this technique are short 30-gauge for posterior teeth and extra-short for
anterior teeth.

4.6.2 Palatal tissue’s Anesthesia:

Papillary-Interdental Anesthesia

After anesthetizing the buccal aspect of the tooth (Fig. 4.2), the child is asked to
bite a cotton roll, and the needle is penetrated into the papilla parallel to the occlu-
sal plane; the solution is injected until the blenching of the palatal aspect is
achieved.
4 Assessment and Management of Pain in Pediatric Dentistry 35

Fig. 4.2 Palatal tissue’s

anesthesia

4.7 Inferior Alveolar Nerve Block (IANB)

This technique is recommended when multiple teeth will be treated in the mandib-
ula and when a deep operative or surgical procedure will be undertaken for man-
dibular primary and permanent molars. An advantage of this technique is that with
the penetration of a single needle, we anesthetize the buccal and lingual aspects.
According to Melamed [8], the IANB, commonly (but inaccurately) referred to
as the mandibular nerve block, is the second most frequently used technique (after
infiltration) and possibly the most important injection technique in dentistry.
Unfortunately, this technique is also the most frustrating, as evident by the highest
proportion of clinical failures, even when administered properly. A suggested rea-
son for failure is inadequate mouth opening. In this situation, the inferior alveolar
nerve, which descends, is relaxed a distance from the medial wall of the ramus; this
results in inadequate anesthesia. In contrast, when the mouth opening is adequate,
the nerve is flushed against the medial wall of the ramus and at the target area.
(Failure of inferior alveolar nerve block: exploring the alternatives [11]). Therefore,
the use of a mouth prop is recommended to achieve adequate mouth opening during
the injection time.
As the soft tissues will remain anesthetized up to 180 min, children could bite
their lips and tongue.
The IANB should be complemented with a long buccal nerve block in order to
anesthetize the buccal soft tissues and the periosteum adjacent to the mandibular
molars. A separate injection for buccal anesthesia is not always necessary, as in
young children, the ramus is narrower. Therefore, after mandibular block anesthe-
sia, the buccal tissue usually becomes anesthetized; this is probably due to the ener-
vation of the buccal mucosa by nerve fibers that emanate from the mental foramen [7].
36 D. Ram and E. Davidovich

4.8 Computer-Controlled Local Anesthetic Delivery

Computer-controlled local anesthetic delivery (C-CLAD) is a method used to

reduce patient pain during local anesthesia. The computerized device enables con-
trolling the injection speed and the pressure induced during delivery. This technol-
ogy has enabled more comfortable administration of potentially painful injections.
The first C-CLAD device, The Wand, was introduced in 1997. C-CLAD systems
represent substantial change in the manner in which local anesthetic injections are
administered. Accordingly, the operator can focus attention on needle positioning
and insertion, while the motor in the device administers the drug at a reprogrammed
rate of flow. It is likely that greater ergonomic control coupled with fixed flow rates
is responsible for the improved injection experience demonstrated in many clinical
studies conducted with C-CLAD devices in dentistry [8].
At present, several C-CLAD systems are available on the market: The Wand STA
Single Tooth Anesthesia System (Milestone Scientific Inc., Livingston, New Jersey),
Calaject (Aseptico Inc., Woodinville, Washington), and EZ Flow (Denterprise
International Inc., Ormond Beach, Florida) are marketed in the USA, DentaPen and
QuickSleeper are marketed in Europe, and similar devices, such as the Anaeject, are
marketed in Japan.
C-CLAD devices enable comfortable administration of local anesthetics in virtu-
ally all areas of the oral cavity. This is of greatest importance in the palate, where
the level of patient discomfort can be considerable. The nasopalatine nerve block, as
well as other palatal injections (e.g., AMSA, the palatal approach anterior superior
alveolar), can be administered atraumatically. Presumably, any injection technique
with even a remote possibility of being uncomfortable for a patient can be delivered
more comfortably with a C-CLAD device.

4.9 Behavior Management During Local Anesthesia

The authors of a Cochrane systematic review published in 2020 concluded that due
to variations in methodology and the nature/timing of outcome measures, the evi-
dence is insufficient as to the best interventions for increasing acceptance of local
anesthesia in children [12]. This study [12] examined several behavior management
techniques before, during, and after administration of local anesthesia. These
included the use of equipment intervention (audiovisual aids such as audiovisual
glasses, television, music), intervention by the dentist, video modeling, and hypno-
sis. The authors of that study could not demonstrate a superior technique.
The authors of this chapter recommend the use of traditional behavior manage-
ment techniques that include Tell-Show-Do and distraction, with emphasis on the
use of modern equipment for distraction such as screens (television, audiovisual
glasses, mobile phone, and others).
4 Assessment and Management of Pain in Pediatric Dentistry 37

There is no agreement in the literature regarding a preferable jaw for the first
treatment and whether the anesthetic technique affects a child’s behavior at the fol-
lowing dental visit. Ram et al. concluded that more adverse reactions were observed
in children following mandibular block than maxillary infiltration, yet this did not
result in increased opposition to attend a subsequent dental appointment [13].
During administration of local anesthesia, the dentist should explain to the child
what is going to happen, that only the tooth is going to sleep (the child will not be
going to sleep) and that a tickling or funny sensation will be felt in the area.
The technique of local anesthetic administration is an important consideration in
pediatric patient behavior guidance. Age-appropriate nonthreatening terminology,
distraction, topical anesthetics, proper injection technique, and pharmacologic man-
agement can contribute to a positive experience during administration of local anes-
thesia. In pediatric dentistry, the dental professional should be aware of proper
dosage (based on body weight) to minimize the chance of toxicity and the pro-
longed duration of anesthesia, which can lead to self-inflicted tongue or soft-tissue
trauma [6].
One study found that the region of local anesthetic injection did not affect chil-
dren’s behavior during and immediately after dental treatment [13].
Testing the effectiveness of local anesthesia is imperative. The dental procedure
should never start before ensuring that the relevant area is completely anesthetized.
Pain is a subjective feeling; if a child complains about pain, we should always
believe the child’s feeling and check the anesthesia.

4.10 Materials and Solutions

The most common solutions used in pediatric dentistry are lidocaine, articaine, and
mepivacaine (Table 4.1).

Table 4.1 Materials and solutions

Dose Duration of anesthesia
Lidocaine 2% Pulpal: 60 min
   Epinephrine 1:100.000    Soft tissue: 3–5 h
   Max dose 4.4 mg/kg
   Cartridge contains 36 mg
Mepivacaine 3% Pulpal: 20–40 min
   No vasoconstrictor    Soft tissue: 2–3 h
   Max dose 4.4 mg/kg
   Cartridge contains 54 mg
Articaine 4% Pulpal: 60–90 min
   Epinephrine 1:100.000    Soft tissue: 3–8 h
   1:200.000
   Max dose 5 mg/kg (5–12 years old)
   7 mg/kg >12 years old
   Cartridge contains 72 mg
38 D. Ram and E. Davidovich

4.11 Side Effects and Complications

A number of potential complications are associated with the administration of local

anesthetics. These complications can be classified as local—in the region of the
injection—and systemic [8].

4.12 Toxicity

Young children are more likely to experience toxic reactions because of their lower
body weight. The potential for toxic reaction increases when local anesthesia is
used in conjunction with sedation medication.
Local anesthetic overdose results in excitation, followed by depression of the
central nerve system and to a lesser extent of the cardiovascular system (CVS).
Overdose reactions and allergy are important topics that should be considered when
anesthetizing a child. When administered properly and in therapeutic dosages, local
anesthetics cause little or no clinical evidence of depressing the central nervous
system (CNS) or the CVS. However, signs and symptoms of selective CNS and
CVS depression develop with increased blood levels in the cerebral circulation or
myocardium. Early subjective symptoms of CNS toxicity include dizziness, anxi-
ety, and confusion and may be followed by diplopia tinnitus, drowsiness, and tin-
gling. Objective signs of CNS toxicity include muscle twitching, tremors,
talkativeness, slow speech, and shivering followed by overt seizure activity.
Unconsciousness and respiratory arrest may occur. Local anesthetic toxicity should
be avoided, by following proper injection technique and calculation of maximum
recommended dosages based on the child’s weight.

4.13 Allergy

Allergies to solutions used in local anesthesia can manifest as urticaria, dermatitis,

angioedema, fever, photosensitivity, and anaphylaxis. Patients may exhibit a reac-
tion to the bisulfite preservative added to the anesthetic containing epinephrine. The
risk of allergy to local anesthetics in pediatric patients is overestimated. In addition
to negative skin tests, a subcutaneous challenge with the particular local anesthetic
should be performed. Patients with positive skin tests should undergo a skin test and
challenge with an unrelated local anesthetic, in search of an alternative drug. This
approach will minimize the number of children who are wrongly denied the benefits
of LA use in future procedures [14].
4 Assessment and Management of Pain in Pediatric Dentistry 39

4.14 Trauma to Soft Tissue

The duration of the soft-tissue anesthesia is greater than the pulpal anesthesia, and
the effect persists for hours after the injection. Self-induced soft-tissue injuries fol-
lowing accidental biting or chewing of the lip, the tongue, or the cheek are reported
as complications of the administration of local anesthesia [8]. As no pain is felt, a
child may bite soft tissues out of curiosity associated with the unfamiliar sensation
of numbness or inadvertently during postoperative eating or sleeping. These injuries
commonly present with localized swelling, edema, and pain. Most lesions are self-­
limiting and heal without complications; however, swelling may cause anxiety in
the parents, and they might wonder if the accident occurred during the treat-
ment [15].
The sensation of the numbed tissues should be emphasized to the parents, as well
as the need to avoid biting and scratching the anesthetized tissues. Ram et al. dem-
onstrated that licking an ice popsicle after dental treatment with local anesthesia
reduces the feeling of discomfort and the biting of soft tissue and self-mutilation
[16, 17].
In summary, in deciding to deliver local anesthesia to a child, we should adopt a
holistic approach that considers the child’s age, medical condition, personality, den-
tal experience and family, and the treatment required to tailor the optimal technique
and solution to the child.

References
1. Davidovich E, et al. Levels of stress among general practitioners, students and specialists in
pediatric dentistry during dental treatment. J Clin Pediatr Dent. 2015;39(5):419–22.
2. Klingberg G, et al. Local analgesia in paediatric dentistry: a systematic review of techniques
and pharmacologic agents. Eur Arch Paediatr Dent. 2017;18(5):323–9.
3. Mundiya J, Woodbine E. Updates on topical and local anesthesia agents. Oral Maxillofac Surg
Clin North Am. 2022;34(1):147–55.
4. Dean, J.A., et al., McDonald and Avery's dentistry for the child and adolescent. Eleventh edi-
tion. ed. 2022, St. Louis, Missouri: Elsevier. xviii, 734.
5. Lehr J, Masters A, Pollack B. Benzocaine-induced methemoglobinemia in the pediatric popu-
lation. J Pediatr Nurs. 2012;27(5):583–8.
6. Use of Local Anesthesia for Pediatric Dental Patients. Pediatr Dent. 2018;40(6):274–80.
7. Kupietzky A. Wright’s behavior management in dentistry for children. Wiley-Blackwell:
Hoboken; 2021. p. 1. online resource
8. Malamed, S.F., Handbook of local anesthesia. 7th edition. ed. 2019, St. Louis, MO: Elsevier.
9. Oulis CJ, Vadiakas GP, Vasilopoulou A. The effectiveness of mandibular infiltration com-
pared to mandibular block anesthesia in treating primary molars in children. Pediatr Dent.
1996;18(4):301–5.
10. Sharaf AA. Evaluation of mandibular infiltration versus block anesthesia in pediatric dentistry.
ASDC J Dent Child. 1997;64(4):276–81.
11. Madan GA, Madan SG, Madan AD. Failure of inferior alveolar nerve block: exploring the
alternatives. J Am Dent Assoc. 2002;133(7):843–6.
40 D. Ram and E. Davidovich

12. Monteiro J, et al. Interventions for increasing acceptance of local anaesthetic in children and
adolescents having dental treatment. Cochrane Database Syst Rev. 2020;2:CD011024.
13. Davidovich E, et al. The influence of location of local anesthesia and complexity/dura-
tion of restorative treatment on children’s behavior during dental treatment. Pediatr Dent.
2013;35(4):333–6.
14. Peroni D, et al. Allergic manifestations to local anaesthetic agents for dental anaesthesia in
children: a review and proposal of a new algorithm. Eur J Paediatr Dent. 2019;20(1):48–52.
15. Bagattoni, S., et al., Self-induced soft-tissue injuries following dental anesthesia in children
with and without intellectual disability. A prospective study. Eur Arch Paediatr Dent, 2020.
21(5): 617–622.
16. Ram D, et al. Unsweetened ice popsicles impart a positive feeling and reduce self-mutilation
after paediatric dental treatment with local anaesthesia. Int J Paediatr Dent. 2010;20(5):382–8.
17. Ram D, et al. The use of popsicles after dental treatment with local anesthesia in pediatric
patients. J Clin Pediatr Dent. 2006;31(1):41–3.
Behavioral Approaches as an Adjunct
for Pulp Therapy 5
Janice A. Townsend and Ari Kupietzky

Contents
5.1 Introduction 42
5.2 Patient Assessment 44
5.3 Informed Consent and Parental Guidance 44
5.4 Basic Behavior Guidance Techniques 45
5.4.1 Communication 45
5.4.2 Tell-Show-Do 46
5.4.3 Distraction 47
5.4.4 Relaxation Exercises 48
5.4.5 Nitrous Oxide 48
5.5 Pain Validation 48
5.6 Management of Challenging Situations 48
5.6.1 Inability or Refusal to Cooperate 48
5.6.2 Inadequate Pain Control 49
5.7 Recovery After a Difficult Appointment 49
5.8 Conclusions 50
5.8.1 Case 5.3 51
References 52

J. A. Townsend (*)
Department of Dentistry, Nationwide Children’s Hospital, Columbus, OH, USA
Division of Pediatric Dentistry, The Ohio State University College of Dentistry,
Columbus, OH, USA
e-mail: [email protected]
A. Kupietzky
Department of Pediatric Dentistry, The Hebrew University—Hadassah School of Dental
Medicine, Jerusalem, Israel
e-mail: [email protected]

© The Author(s), under exclusive license to Springer Nature Switzerland AG 2023 41

A. B. Fuks et al. (eds.), Contemporary Endodontics for Children and
Adolescents, https://doi.org/10.1007/978-3-031-23980-9_5
42 J. A. Townsend and A. Kupietzky

5.1 Introduction

Dentistry is one of the only areas in healthcare where surgical procedures are rou-
tinely performed on children with minimal or no sedation. Behavior management or
guidance is “the means by which the dental team effectively and efficiently per-
forms treatment for a child and at the same time instills a positive dental attitude”
[1]. Behavior guidance is a spectrum that includes nonpharmacologic and pharma-
cologic techniques, often in dynamic interplay as shown in Fig. 5.1. Early publica-
tions on behavior guidance were primarily anecdotal in nature, but the field has
evolved to include evidence-based techniques.
Behavior guidance for pulp therapy merits specific focus. Pulp therapy is indi-
cated for extensive carious lesions or dental traumatic injuries, both conditions
associated with pain. Uncontrolled pain increases dental anxiety and unmanaged
anxiety upregulates pain creating a vicious cycle. Pain or trauma may prompt a first
dental visit for a child who has not as yet established a dental home, which is an
unfavorable introduction to the dental setting (Figs. 5.2 and 5.3). In a university-­
based clinic, Agostini found that one quarter of children had an emergency dental
visit as a first visit [2]. Children may be referred for pulp therapy from a general
dentist or dentist less skilled at treating children and may have already had a nega-
tive prior dental visit. Finally, pulp therapy procedures are more technically chal-
lenging than routine operative dentistry and may require lengthier visits, less
tolerance for movement, and the need for repeat visits. In certain clinical situations,
profound dental anesthesia may not be achievable. The benefits of preserving the
dentition and preventing future prosthodontic and orthodontic treatment needs make
the additional behavior management challenges worthwhile. Thus, behavior

Communicative
Behavior Guidance
Audio Visual
Distraction
Nitrous Oxide/
Oxygen Deferred and
Alternative Treatment

Basic

Protective
Stabilization

Sedation
General
Anesthesia

Fig. 5.1 Behavior guidance technique continuum. Source: Nelson (2013). © 2013, Elsevier
5 Behavioral Approaches as an Adjunct for Pulp Therapy 43

ld in pain Stre
Parent / Chi ss
n ed Child
caregiver it o pa
ua

re
t
si

nt
ing

s
ten

Fee
Threa

lings of guilt C
Conflict Tension
bits
ha

om
g

Dentist, dental team dental

pl
n

ic
di

environment
at
ed ee
de orf
nta o
l procedures P

Fig. 5.2 Vicious cycle of poor feeding habits, pain, and parental guilt resulting in conflict between
the family and dental team

Fig. 5.3 Alternative

environment with healthy
feeding practices, lack of on- threaten
s N Child in
pain, and non-threatening nt
e

environment resulting in
ar

sit
ld Happy p

uat

harmony between the

Trust Harmony
ion Health

family and dental team

chi

yf

Parent/Caregiver
py

Dentist, dental
ed
ing ap
practices H
team dental
environment

guidance is central to successful pulp therapy outcomes. Other texts extensively

review behavior management, and the focus of this chapter will be on practical
techniques to manage children and adolescents undergoing pulp therapy procedures.
44 J. A. Townsend and A. Kupietzky

Table 5.1 Intake questionnaire. (Source: Kupietzky (2022). © 2022 Wiley Blackwell)
How do you consider your child is learning? • Advanced in learning
• Progressing normally
• A slow learner
How has your child reacted to past medical/dental • Very well
experiences? • Moderately well
• Moderately poor
• Very poor
How would you rate your own anxiety (nervousness, fear) at • High
this moment? • Moderately high
• Moderately low
How do you expect your child to react in the dental chair? • Very well
• Moderately well
• Moderately poor
• Very poor
Has treatment for this problem been previously attempted? • Yes
If yes, please
elaborate___________
• No

5.2 Patient Assessment

Prior to treating a patient, the dentist should gather historical information to form a
preliminary behavior assessment. Numerous questionnaires exist to assess tempera-
ment, fear, and anxiety, but the simple background questions shown in Table 5.1 can
yield insight into clinical behavior.
Any answers that suggest potential uncooperative behavior should be discussed
with the caregiver where the patient cannot overhear.

5.3 Informed Consent and Parental Guidance

Prior to commencing any pulp therapy procedure, the caregivers of a child must
consent to the treatment. Caregivers must understand the value of preserving teeth
versus extraction, the goals of the visit, the need for subsequent visits, and the den-
tist should set a realistic expectation for behavior. All available treatment options as
well as expected success rates for the various procedures should be presented and
fully discussed. When a child has had a recent trauma or is in pain, it can be difficult
for parents to focus on future planning. However, investing the time to establish this
therapeutic alliance is critical to prevent misunderstandings in the midst of treatment.
The dentist should identify critical events in the procedure and plan decisions in
advance. For example, if behavior is questionable, the dentist and parent may mutu-
ally agree that if movement during the injection creates an unsafe environment, the
procedure will be aborted, and plans for pharmacologic management will be made.
Conversely, a decision may be made in advance that if this type of behavior com-
mences once the pulp is exposed, medical immobilization will be utilized to bring
the procedure to a safe completion. Although a caregiver can withdraw consent at
5 Behavioral Approaches as an Adjunct for Pulp Therapy 45

any time, this level of planning helps the parent anticipate potential challenges and
commit to a plan of action. All possibilities shall be previously discussed so that
lengthy discussions while the child is lying on the dental chair will be avoided.
Providers must also clearly set expectations for caregivers’ participation before
starting the procedure. Without guidance, caregivers’ attempts to comfort their chil-
dren may inadvertently promote distress. This may include interfering with or con-
tradicting the instructions from the dentist, criticizing the child, or providing
uninformative reassurance. The dentist can use data from the assessment question-
naire to probe the caregiver’s mindset. If a caregiver identifies they are nervous or
do not have confidence in their child’s ability to cooperate, then the dentist can
inquire if there is someone who can better support the child during the appointment.
If there is no one else, the dentist can give the parent the option of being a silent
observer while operation is ongoing or waiting outside so the caregiver’s own anxi-
eties do not negatively affect the patient. Parents typically respond well to specific
instructions on their conduct in the dental environment [3, 4]. Conversely, a parent
that demonstrates a natural tendency to engage in coping promoting behaviors (i.e.,
makes constructive, positive comments, stays silent while the dentist and staff talk)
can be used as an asset for distraction and comfort, especially for children with
special healthcare needs.

5.4 Basic Behavior Guidance Techniques

5.4.1 Communication

Open, clear communication between the child and dentist is essential to success.
The dentist should establish rapport with the child or adolescent before initiating
any dental procedures. For young children, the dentist may compliment their clothes
or shoes. For older children and adolescents, the dentist may inquire about school or
extracurricular activities. These initial conversations should be brief but establish a
positive connection and an interest in the patient. The dentist can continue discuss-
ing the topic as they move through the typical steps of the appointment (i.e., reclin-
ing the chair, examining the teeth, etc.) stopping for explanations when needed.
Quiet, calm talk from the dentist can help distract a potentially anxious patient. For
timid patients, the caregiver may answer questions on the child’s behalf, but it is
important to keep all aspects of the conversation patient-centered. The dentist
should accompany this communication with frequent, direct eye contact to maintain
attention and to monitor for anxiety and pain.
All patients benefit from short, direct instructions, and these are especially ben-
eficial for young children, patients who are non-native speakers, or children with
special healthcare needs. Positive instructions are easier for young children to com-
prehend. For example, “Open your mouth very wide” is preferred to “Don’t close.”
Compliance with instructions should be rewarded with immediate, specific, positive
verbal praise (“You are my best patient today because you are keeping your mouth
open wide”).
46 J. A. Townsend and A. Kupietzky

“Active ignoring” or “selective attention” should be employed for children

engaging in minor, annoying behaviors [5]. By telling a child to stop whimpering,
they are inadvertently “rewarding” the behavior by giving it your attention. Instead,
the focus should be on rewarding positive behaviors through attention and ignoring
negative behaviors, when feasible.
Behavior that interferes with treatment should be addressed by utilizing voice
control. Voice control has been mistakenly characterized as yelling at or berating
children. Instead, the dentist gains the child’s attention through modulating their
own voice be it with altered volume, pace, or tone [6]. The child also benefits from
an explanation about how complying with instructions will benefit them in immedi-
ate and concrete ways. For example, “If you move when I am touching your teeth, I
may accidentally touch your gums, which would hurt. When you sit still, I can be
gentle.” Subsequent compliance with these commands should be immediately
praised in a warm, friendly tone.
Patients benefit from a signaling mechanism, typically a raised hand or thumb, in
case they need to communicate when they have instruments in their mouth; this has
been termed as “stop signals” or “enhancing control” [6, 7]. The dentist should
avoid reference to discomfort as a reason to signal (i.e., “Raise your hand if any-
thing hurts”), as the patient will be constantly monitoring for pain increasing hyper-
sensitivity and anxiety. Instead, the dentist can say “Raise your hand if you need to
tell me anything.” If a patient overuses signals to delay care, the dentist may have to
limit how often they will pause, but this technique is usually well received and
builds confidence in the dentist-patient relationship.

5.4.2 Tell-Show-Do

In tell-show-do, procedures are described to patients using developmentally appro-

priate, non-threatening terminology. Relevant instruments are shown to the patient,
and the child is able to touch the instrument in a safe manner. Finally, the proce-
dure is performed. For endodontic therapy, rubber dam use has been associated
with decreased stress, and with practice, rubber dam placement is fast and leads to
optimal visualization, protects the tissues, prevents aspiration, and encourages
nasal breathing, which promotes the response to nitrous if being used [8]. Tell-
show-do is an ideal technique to promote acceptance of the rubber dam. The rubber
dam clamp can be introduced as a “ring” and placed on the child’s finger. They
should be told that the ring will be snug so it will not fall out and given a small
squeeze on the finger or forearm to prepare them for the tight sensation. Next, the
rubber dam on the frame is introduced as a “trampoline” for the “sugar bugs” to
jump on or as a “raincoat” to keep the teeth dry. For single tooth isolation, it may
be easier to place the clamp first (with 18 in./45 cm of floss for easy retrieval) and
then to slip the rubber dam around the bow and below the wings. The noise of slip-
ping the rubber dam over the frame can be explained as the sound of fastening
buttons on the raincoat.
5 Behavioral Approaches as an Adjunct for Pulp Therapy 47

To reduce alarm from the sharp appearance of instruments such as files, the
patient can be shown a paper point. The dentist may let the child hold the paper
point and tell them that today you will be using a number of things that look sharp,
but they are not “pokey” and that this is an example. Dentists must take safety pre-
cautions in case of disruptive behavior and should ligate any small instruments such
as broaches and files with floss. Even with rubber dam isolation, there is risk of
swallowing or aspiration if a child becomes combative.

5.4.3 Distraction

Of all the behavior guidance techniques, distraction has the strongest evidence of
efficacy in improving cooperation and reducing pain perception [9]. Distraction can
be verbal, visual, and physical; a combined approach is best. For an initial appoint-
ment with a child unfamiliar with dentistry, the dentist must explain new procedures
or instruments and may want to use verbal distraction. In addition to tell-show-do,
the dentist can use storytelling or a nonverbal guessing game. For example, the
dentist may say “I bet I can guess your favorite color. Blink once if my guess is
wrong and twice if it is right.” These games can engage the child’s attention through
difficult parts of the procedure. Some children find counting soothing, and when
accompanied by a small break, this gives opportunities for escape.
Once a child is more familiar with the dental setting, they may prefer audiovisual
distraction utilizing wrap-around eyeglasses or a screen mounted in viewing dis-
tance [10, 11]. Use caution with earphones or buds that block the dentist’s voice
entirely so the patient is not startled by new stimuli. Adolescents tend to prefer
bringing their own music to appointments and use of headphones.
Physical distraction can help relieve pain during potentially uncomfortable pro-
cedures. Gentle cheek shaking during injection activates nerves that conduct non-­
noxious stimuli to close a neural “gate” to prevent nociception [12, 13]. According
to “gate theory,” vibrating the cheek or the surrounding mucosa tissues may reduce
the sensation of pain as postulated by the gate control theory of pain management,
which suggests that pain can be reduced by simultaneous activation of nerve fibers
through the use of vibration [14]. Vibrating devices have potential to mitigate pain
but have mixed results and should not impair the dentist’s ability to maintain ade-
quate head control [15]. Children may enjoy having a stuffed animal or squishy toy
that they can squeeze to distract them from the discomfort. Finally, engaging in
appropriate movements such as circling a foot, raising a leg, or writing in the air
using a leg serves as effective distraction for challenging portions of the procedure
for limited amounts of time [16].
Some parents are excellent partners in distraction by playing music or engag-
ing in patient-centered discussion with the dental team about the child’s interests
and accomplishments. As long as the parent allows instructions to come only
from the dentist and conversation remains patient focused, this presence can be
reassuring.
48 J. A. Townsend and A. Kupietzky

5.4.4 Relaxation Exercises

For anxious patients, management techniques that promote slow, deep breathing are
beneficial [17]. Diaphragmatic breathing, or paced deep breathing, leads to a
decrease in sympathetic activation, resulting in physiologic changes such as
decreased heart rate [18]. These exercises can be introduced in a number of ways
based on the child’s developmental level. For younger children, a bubble blower can
be introduced prior to the procedure to practice big, deep breaths [19]. Once the
appointment starts, they can continue to practice this breathing. A hand can be
placed on the abdomen to encourage “belly breathing” or deep breathing. The den-
tist can take breaths together and count slowly to lower the rate of breathing.

5.4.5 Nitrous Oxide

If available, nitrous oxide is a valuable adjunct to pulpal therapy although it is no

replacement for behavior management and profound local anesthesia. Nitrous oxide
reduces anxiety, raises the pain reaction threshold, obtunds the gag reflex, and can
encourage deep breathing and support distraction techniques [20–22].

5.5 Pain Validation

Some patients have a difficult time differentiating stimuli such as pressure or hand-
piece vibration from pain. Prior to any operative procedure, the dentist should run
the handpiece in the mouth without touching the tooth to gauge the child’s reaction.
Teeth with irreversible pulpitis have been characterized as “hot teeth” and can be
painful even with excellent anesthesia technique [23]. The dentist can apply refrig-
erant (Hygienic® Endo Ice®, Coltene/Whaledent Inc., Cuyahoga Falls, Ohio, USA)
to a tooth following local anesthesia and prior to any procedures. If the tooth
responds to cold, additional measures are indicated. If there is no sensation, the
dentist can proceed with gently using a slow-speed bur on intact enamel [24]. If
there is a negative reaction, it is likely the result of procedural anxiety versus true
perception of pain. For more information on local anesthesia, see Chap. 4.

5.6 Management of Challenging Situations

5.6.1 Inability or Refusal to Cooperate

Some children or adolescents are unable or unwilling to cooperate for dental treat-
ment. This behavior, especially in the circumstances of recent trauma or pain, has a
foundation at least partially in dental fear. However, inappropriate child/adult rela-
tionships, desire for attention, and attempts to assert dominance/defiance can result
5 Behavioral Approaches as an Adjunct for Pulp Therapy 49

in a child that is mistrustful or unwilling to engage in fear reduction exercises and

thus cannot cope with treatment. Management of these patients is dependent on
patient factors such as age, cognitive development, and type/intensity of response as
well as tooth-related factors such as complexity of needed ideal treatment and risks
of alternative treatment.
The first step in managing any uncooperative behavior is to establish communi-
cation. For patients with exaggerated externalizing behaviors, sometimes dubbed as
“temper tantrums,” a time-out may curtail this behavior and open communication
[25]. For shy or timid children, gentle communication and gradual exposure to the
environment can build trust. For these children, humor, such as asking them to take
off their shoes so you can count their teeth, can result in wide open mouths eager to
prove where teeth are found [26, 27].
If behavior management strategies are inadequate to establish a safe environment
for complex procedures, the provider should consider deferring treatment until it
can be safely performed under sedation or general anesthesia. In patients with
severely carious first permanent molars, which would require multiple endodontic
therapy and restorative visits per tooth, alternatives such as extraction with second
molar substitution could be considered [28].

5.6.2 Inadequate Pain Control

In some circumstances, local anesthesia is either exquisitely painful or cannot be

reliably obtained at all due to infection. For single-rooted necrotic teeth with exten-
sive local swelling, pulpal access may be more comfortable without local anesthe-
sia. Sensibility testing should occur prior to access to confirm lack of innervation,
and conservative instrumentation should be utilized. Upon access to the pulp cham-
ber, these patients may communicate a sense of released pressure or immediate pain
relief. Definitive cleaning and shaping can occur at a later date when adequate peri-
apical anesthesia is possible. This technique may be used in molars but is not as
predictable as vital pulp tissue may still reside in one canal.
In circumstances of “hot teeth” where pain control is inadequate, the dentist may
manage with analgesics and antibiotics, if indicated, until the infection is no longer
interfering with treatment or until sedation or general anesthesia is possible.

5.7 Recovery After a Difficult Appointment

Dentists often treat children and adolescents who have had previous negative
appointments. These may have occurred with a previous dentist or in their own
office when an emergency necessitated treatment in an un-ideal situation or a patient
lost cooperation during a visit. Locker et al. [29] found slightly over half of patients
with dental anxiety had onset in childhood and aversive events in childhood were
most strongly associated with anxiety.
50 J. A. Townsend and A. Kupietzky

Previous negative experiences do not have to define a child’s future relationship

with dental care. Appropriate management can prevent or reframe unpleasant mem-
ories with the goal of instilling a positive dental attitude.
Negative appointments should be discussed with parents as soon as feasible. If
the unpleasant visit happened elsewhere, discussion of appointment details should
be part of the intake interview where the child cannot overhear. If it happens in your
office, the dentist should engage with the caregiver immediately after the appoint-
ment. If it is possible to separate the child from the parent, it is preferable this con-
versation take place in person, and if they cannot be separated, a phone call should
be scheduled the same day as the appointment. At this time, the dentist should ask
open-ended questions about the appointment to assess any parental concerns. These
are best addressed immediately to assuage any apprehensions about the visit before
they have time to turn to dissatisfaction. The dentist can communicate that the
appointment was difficult, but necessary, empathize that parenting is demanding,
and compliment the parent on specific ways they helped the child cope. Next, the
dentist and parent should discuss communication strategies. Caregivers should
never bring up difficult aspects of the appointment in the future. A toddler may not
remember they required active immobilization during an injection, but if they are
told the story about being “held down” repeatedly, this “memory” will become
vivid. For school-age children and adolescents who vocalize fear, communication
should focus on successful aspects of the visit and how much the team cares about
the patient.
Pickrell et al. [30] described a formal process of memory restructuring that can
help reframe unpleasant visits. This technique can be taught to parents new to your
office or introduced following an avoidable, difficult appointment. First, a visual
reminder of a time the child was happy at the dentist is used. This could be the initial
patient photo or even a picture of the child brushing their teeth. Second, the child is
asked to verbalize something positive about their previous visit and to practice shar-
ing this information with a caregiver. The dental team then reinforces this positive
feedback with specific examples of cooperation such as the child’s ability to hold
hands in their lap. Finally, the child demonstrates these behaviors, demonstrating
they can achieve a successful dental visit. Pickrell [30] found that children who
underwent this process were significantly less likely to report pain for fear of an
injection.

5.8 Conclusions

Management of endodontic treatment in children and adolescents is inherently chal-

lenging due to the complexity of procedures and increased likelihood of pain. With
proper communication, use of behavior management techniques, and appropriate
post-visit guidance, endodontic therapy can be successfully performed on a wide
spectrum of patients. If a dental home is established prior to the endodontic treat-
ment, the environment facilitates optimal behavior. Unfortunately, children who
appear with acute pain usually do not have a dental home and are unlikely to return
5 Behavioral Approaches as an Adjunct for Pulp Therapy 51

ECC

The dental home may assist in

Dental pain Parental anxiety
breaking the dental fear cycle

Invasive dental procedures

Unfamiliar & threatening

Early painful dental experience dental/hospital environment

Fearful patient

Future dental behavior

Future dental health

Fig. 5.4 A dental home is key to breaking the cycle of dental pain and dental fear

for routine exams without guidance. If a dental home has not been established prior
to treatment, a child’s best way to overcome a prior negative dental experience is to
develop a healthy pediatric dental treatment triangle with a kind dentist and warm
dental team (Fig. 5.4).

5.8.1 Case 5.3

Two 4-year-olds arrived at the pediatric dentist’s office following a collision of

heads at nursery school. Both children had bleeding from the mouth and were
accompanied by their parents. Sue had been at the dentist initially at age two and
had since returned for a checkup the previous year. Jack had never been to any den-
tist, and this emergency visit was the first for both himself and his mother. Jack was
crying and very frightened, and his mom was visibly upset and tense. Conversely,
Sue was a little nervous but was familiar with the office, staff, and dentist. She was
looking forward to receiving the prize to be given later. Her mom remembered being
told by the dentist that such incidents might occur and are indeed expected. “Kids
will be kids. Maybe that is why they grow up with baby teeth.” On the other hand,
Jack’s mom reacted aggressively toward the dentist when she was told that her son’s
lip was indeed lacerated but that his teeth were not fractured due to the fall; rather
they were severely decayed and only appeared broken. The mother had given Jack
a baby bottle of apple juice to calm him. She was shocked when told that Jack
needed extensive dental work not only on his front teeth but also his molars, as they
showed advance signs of ECC.
52 J. A. Townsend and A. Kupietzky

Sue was discharged after an X-ray. Jack refused to take an X-ray and was to
return for restorative treatment under general anesthesia, his parent’s preference.

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The Caries Lesion: Diagnosis,
Decision-­Making, 6
and Recommendations for Lesion
Management

Fernando Borba de Araujo , Marisa Maltz ,

Cleber Paradzinski Cavalheiro ,
and Tathiane Larissa Lenzi

Contents
6.1 Introduction 55
6.2 Caries Disease Development and Control Strategies 56
6.3 Caries Diagnosis 57
6.4 Strategies of Dental Caries Lesion Management 60
6.5 Treatment Options for Initial, Moderate, and Extensive Caries Lesions 61
6.6 Concluding Remarks 67
References 68

6.1 Introduction

Dental caries is a biofilm-mediated, diet modulated, multifactorial, noncommuni-

cable, dynamic disease, resulting in net mineral loss of dental hard tissues [1]. It is
affected by biological, behavioral, psychosocial, and environmental factors. Caries
lesions develop as a consequence of this process.
Caries diagnosis is the clinical judgment integrating available information,
including the detection and assessment of caries signs (lesions), to determine pres-
ence of the disease. The main purposes of clinical caries diagnosis are to achieve the
best health outcome for the patient by selecting the best management option for

F. B. de Araujo (*) · C. P. Cavalheiro · T. L. Lenzi

Department of Surgery and Orthopedics, Faculty of Dentistry, Federal University of Rio
Grande do Sul, Porto Alegre, RS, Brazil
e-mail: [email protected]
M. Maltz
Preventive and Social Dentistry, School of Dentistry, Federal University of Rio Grande do
Sul, Porto Alegre, RS, Brazil

© The Author(s), under exclusive license to Springer Nature Switzerland AG 2023 55

A. B. Fuks et al. (eds.), Contemporary Endodontics for Children and
Adolescents, https://doi.org/10.1007/978-3-031-23980-9_6
56 F. B. de Araujo et al.

each lesion type, to inform the patient, and to monitor the clinical course of the
disease [2, 3]. Minimally invasive interventions have been proposed for caries man-
agement, comprising early detection, preventive procedures, and minimally inva-
sive treatment procedures [4]. This chapter will discuss aspects related to caries
diagnosis, decision-making, and recommendations for management of initial, mod-
erate, and extensive caries lesions reaching the outer half of dentin. Deeper dentin
caries lesions will be addressed in Chap. 10.

6.2 Caries Disease Development and Control Strategies

Biofilms are complex microbial communities embedded in a matrix of self-­produced

polymer substances. Biofilm formation constantly occurs both on smooth surfaces
and on more retentive and anatomically complex areas, and cannot be avoided. The
metabolic activities of the active bacterial deposits, favored by the frequent con-
sumption of fermentable carbohydrates, especially sucrose, affect the underlying
tooth surface, resulting, over time, in irregular pH fluctuations that can result in
mineral loss and establishment of the disease. There is evidence that the first clinical
signs of enamel demineralization are observed after drying of the surface after only
two weeks from the beginning of biofilm construction [5]. However, after a single
week of uninterrupted biofilm formation, it is already possible to detect increased
enamel porosity, which becomes more obvious over time [5, 6]. After three or four
weeks, opaque areas can be observed even without drying of the surface, being
located in the regions covered by the biofilm and following the direction of the
enamel prisms [7]. The detection of initial caries lesions represents a major chal-
lenge for clinicians, because such lesions may go undetected or may be mistaken for
defects in enamel development, such as fluorosis or hypomineralization. However,
the rate of progression of these is relatively low, especially in children who do not
present dentin cavitation [8]. Currently, according to the best available evidence, the
detection of initial caries lesions must be part of the clinical routine, so that thera-
peutic measures can be taken to further reduce the risk of progression of these
lesions. If the disease is not controlled, the formation of dentin cavitation is the
natural consequence that leads, in the absence of treatment, to tooth loss. Although
biofilm is constantly formed and the demineralization and remineralization process
cannot be prevented, the effect of the biofilm on the dental surface can be decreased
by control measurements, and metabolic processes can be modified. The develop-
ment and progression of caries lesions can be prevented or controlled, regardless of
the presence of cavitation and patient age. Caries management consists of actions
taken to interfere with mineral loss at all stages of the caries disease [9], including
both operative and non-operative interventions. Because of the continuous de/rem-
ineralization processes, caries control needs to be sustained throughout life.
Strategies for caries management include population and/or individual targeted
approaches. According to the World Health Organization, population-based strate-
gies should prioritize common risk factors with other noncommunicable diseases
associated with excessive sugar consumption, such as cardiovascular disease,
6 The Caries Lesion: Diagnosis, Decision-Making, and Recommendations for Lesion… 57

diabetes, and obesity [10]. In this context, practices related to lifestyle, such as
healthy diet and improvements in social determinants, such as educational level,
housing conditions, and access to health services, all impact these diseases.
Individual-based strategies are focused on the specific individual’s caries risk.
These approaches, however, should be implemented only after proper clinical
examination and classification of the caries lesions based on severity and activ-
ity status.
The presence of active caries lesions reflects the mineral imbalance, favoring the
mineral loss over gain. Therefore, measures for controlling etiological factors (diet
and biofilm) and those that interfere with the disease process, such as fluorides sup-
ply, aim to re-establish the balance between episodes of mineral loss and gain and
are essential to arrest caries lesion progression. The disease may be controlled
exclusively through the treatment of caries lesions or necessitate specific comple-
mentary interventions, described throughout this chapter.

6.3 Caries Diagnosis

Caries diagnosis process must take into account not only caries lesion detection but
also the etiologic factors of dental caries and caries activity as manifested by the
lesions.
The best method for caries lesion detection and assessment is visual inspection
aided by a ball-ended probe [11] and must be performed for all patients. The use of
indices, such as the international caries detection and assessment system (ICDAS),
improves the diagnosis process mainly in terms of sensitivity and reliability [12].
The presence, severity, and activity of lesions must be assessed through visual
inspection. The most widely used adjunct method for detecting caries lesions is the
radiographic examination. Its implementation as an adjunct to visual inspection
facilitates the monitoring of lesion progression [13, 14] and improves the estimate
of the depth of the lesion rather than relying on visual inspection. However, the
method tends to underestimate the actual mineral loss from the lesion and is not
suitable for detecting the early stages of lesion development [13].
Caries lesion activity assessment seeks to differentiate caries lesions deemed
active from those deemed inactive in order to provide optimal care planning aimed
to arrest active lesions. Activity status of a caries lesion is defined by surface char-
acteristics [15]. Clinical surface features, such as change of texture, translucency,
and color, and other factors such as presence of thick plaque and plaque stagnation
areas as well as gingivitis all help assess whether a lesion is progressing or non-­
progressing/arrested [16–18].
On clinical examination, the first signs of tooth demineralization are visualized
as whitish opaque areas, which become even whiter and more evident as the surface
dries. These lesions, when there is still no loss of surface continuity, are classified
as active non-cavitated lesions (ICDAS scores 1 and 2). If the process is not con-
trolled and the lesions progress, the surface layer ruptures, and cavitated enamel
lesions (ICDAS score 3) are created, preserving the same clinical characteristics
58 F. B. de Araujo et al.

that indicate the presence of activity (Fig. 6.1a) (white, opaque, and rough enamel).
If the disease process is controlled, enamel lesions may assume clinical characteris-
tics of inactive lesions (Fig. 6.1b), with recovery of gloss and surface smoothness.
They can maintain their whitish appearance, take on a darker or brownish color-
ation, or even disappear due to polishing/superficial wear. Lesions closer to the
cervical margin tend to be active, whereas enamel lesions that are distant from the
margin tend to be inactive. Teeth in infra-occlusion are more likely to have active
lesions because of the greater propensity for biofilm accumulation. Underlying dark
shadow lesions from dentin (Fig. 6.2) are classified as ICDAS score 4 and present
clinically as discolorations from the dentin in different shades of gray, blue, or
brown, visible through the translucency of the enamel, with or without localized
enamel breakdown [19]. Despite their clinical appearance, which in many situations
leads the clinician to consider a large involvement of the coronal dentin, studies

a b

Fig. 6.1 Active initial caries lesion on the occlusal surface (a). Inactive caries lesion (b)

Fig. 6.2 Underlying dark

shadow lesions from dentin
in primary molars
6 The Caries Lesion: Diagnosis, Decision-Making, and Recommendations for Lesion… 59

have shown that most underlying dark shadow lesions (67.4–78.9%) in permanent
teeth do not present radiographically detectable radiolucency in dentin [20, 21].
However, these are lesions with a complicated prognosis, since about half of them
progress to more severe stages [8, 22]. Thus, this is one of the situations in which a
complementary radiographic examination is beneficial for determining the depth of
the lesion and, consequently, the best treatment. Dentin caries lesions may be clas-
sified as ICDAS score 5 for distinct cavity with visible dentin or ICDAS score 6 for
extensive distinct cavity with visible dentin (involving more than half of the surface)
[19]. Active dentin caries lesions (Fig. 6.3a) present softened tissue, usually yellow-
ish or brownish with a moist appearance and opacity in the adjacent enamel. The
inactive ones (Fig. 6.3b), on the other hand, have hardened tissue and are usually
darker, with a dry aspect. The hardness criterion prevails over that of coloration and
moisture [23]. The American Academy of Pediatric Dentistry (AAPD) suggests that
radiographs be taken in all situations where tooth surfaces cannot be visualized,
regardless of signs and symptoms [24]. However, the current clinical guidelines of
the European Academy of Paediatric Dentistry (EAPD) [25] and the Brazilian
Association of Pediatric Dentistry [26] note significant changes regarding the radio-
graphic evaluation as a complementary method to detect caries lesions. EAPD [25]
suggests that methods free of ionizing radiation, such as tooth separation and fiber-­
optic transillumination, be used in cases of interproximal lesions detected on clini-
cal examination (cavitated or non-cavitated). It is also suggested that radiographic
examination be indicated in the presence of active caries lesions, both non-cavitated
and cavitated. Furthermore, the authors emphasize that caries risk/activity should be
regularly evaluated as it may influence the indication for initial and monitoring
radiographic examinations. While the EAPD and AAPD recommend radiographs to
monitor caries activity and risk at key ages of the patient (5 years, 8–9 years,
12–13 years, and 15–16 years of age) [24, 25, 27], the guidelines of the Brazilian
Association of Pediatric Dentistry [26] are even more conservative. They focus on
minimizing the use of methods involving ionizing radiation and are aligned with the
minimally invasive dentistry philosophy. They consider radiography only as a

a b

Fig. 6.3 Cavitated denti lesion in the vestibular surface is active (a). Inactive caries lesion on
occlusal surface (b)
60 F. B. de Araujo et al.

confirmatory method recommended for cases in which cavitated or underlying dark

shadow lesions from dentin lesions are detected in the clinical evaluation, and the
clinician is in doubt about the treatment [26, 28–30].
Although proximal lesions can also be assessed by visual evaluation with the aid
of ICDAS, these lesions only become visible by the time they are large enough to
show through the enamel or marginal ridge. A solution to the difficulty in visual
detection of proximal lesions is the use of interproximal radiographic examination
that identifies more lesions than the visual evaluation [31]. The indication for radio-
graphic evaluation of interproximal caries lesions in pediatric dentistry is the pres-
ence of several clinical signs. These signs are the presence of caries lesions and/or
restorations in free smooth surfaces, patient caries activity, and high rates of biofilm
and gingival bleeding, especially in proximal sites. Only 10% of lesions in primary
teeth radiographically located in enamel are cavitated, while 50% of lesions located
in the outer half of dentin already present clinical cavitation [32]. Thus, in the sce-
nario of radiographically detected caries lesions not reaching inner half of the den-
tin, temporary separation with elastic bands has been suggested for direct
visualization of the proximal surface, enabling the evaluation of the presence or
absence of cavitation and consequently the disease activity. Therefore, visual
inspection should be the main method for detection of caries lesions, while comple-
mentary methods such as radiographic examination should be used to assist in treat-
ment planning. New technologies for caries detection have been developed and
studied. Fluorescence-based methods to aid the detection of caries lesions are based
on the principle that decayed dental tissues have their fluorescence properties altered
in comparison to healthy dental tissues [33–36]. However, no significant benefit has
been shown that justifies their use in daily clinical practice [11].

6.4 Strategies of Dental Caries Lesion Management

Before addressing in detail the concepts and guidelines related to the management
of caries lesions, it is necessary to categorize the different strategies for this pur-
pose. For this, we followed the principles of minimally invasive dentistry that clas-
sify the disease control strategies and clinical management of caries lesions into
categories according to the degree of hard tissue invasion [37, 38]:
Noninvasive interventions: These do not involve the removal of hard tooth tis-
sue, only dietary and hygiene guidance and professional fluoride application.
Micro-invasive interventions: When mineral removal of tooth structure is
involved, usually during acid etching. Sealants and resin infiltrants are used.
Invasive interventions: Mechanical removal of tooth tissue by hand instruments
and/or diamond rotary/drill burns.
Two strategies, non-restorative cavity control (NRCC) [39] and Hall technique
[40], do not fit into any of the above categories and are defined as “mixed interven-
tions” [38]. The caries lesion depth is a criterion in clinical decision-making,
although it should never be considered by itself, but adjacent to other criteria.
Identifying whether the lesion is restricted to enamel or involving dentin is a way to
6 The Caries Lesion: Diagnosis, Decision-Making, and Recommendations for Lesion… 61

infer its prognosis, since enamel lesions tend to progress slowly due to the composi-
tion of the tissue [41]. Furthermore, the presence of cavitation may influence lesion
progression since it causes biofilm retention. Thus, when faced with a caries lesion,
the clinician should ask himself, in view of the restorative decision: “Is it a cavitated
lesion?” If the lesion is cavitated, the next question is: “Is the lesion active?” With
active lesions, the first concern is to control the activity, and this leads to a new ques-
tion: “Can the lesion be inactivated without restoration?” To answer this question,
biofilm control settings of the lesion should be evaluated. If a cavitated lesion allows
direct access for brushing, one may choose to postpone the restorative procedure
until the etiological factors are successfully controlled or even choose not to per-
form it (i.e., nonrestorative cavity control). For this to be possible, the patient and
the caretakers need to be motivated to control the caries activity, and this motivation
includes understanding the health process versus caries disease. Once the caries
activity is controlled, the loss of dental structure must be evaluated, considering the
need to establish form, function, and esthetics. Some questions must be pondered:
“Does the destruction due to caries compromise occlusion, chewing, phonation, or
the patient’s social life?” “Does the family or the patient himself demand esthetic
improvement?” “Is there proximity to the dentin-pulp complex causing sensitiv-
ity?” Another aspect to be taken into consideration, in the case of primary teeth, is
how long these teeth will remain in the oral cavity and their strategic importance
[42]. In the context of treatment choice, it is important if the first permanent molar
has already erupted, or not. Caries lesions on proximal surfaces deserve attention
because they cannot be directly visualized. In these cases, it is important that the
clinician understands the correlation between the radiographic image and the clini-
cal aspect for appropriate decision-making, as discussed previously in this chapter.
On proximal surfaces, the presence of a cavity is a crucial factor for the indication
of micro-invasive or invasive strategies, depending on the lesion depth and difficulty
(or even impossibility) of biofilm control by the patient on these surfaces. It is
important to emphasize that restorative procedures, by themselves, do not treat the
disease [43] but aim to control the lesion progression when the removal of biofilm
by the patient is not possible, making it necessary to protect the dentin-pulp com-
plex and restore the integrity of teeth affected by caries [44]. Noninvasive strategies
and monitoring of caries lesions necessarily involve knowledge of the progression
pattern in primary and young permanent teeth, highlighting the importance of vari-
ables such as the presence or absence of cavity, lesion depth, patient’s past and cur-
rent experience of caries activity, access to fluoride, and the patient’s hygiene
pattern.

6.5 Treatment Options for Initial, Moderate, and Extensive

Caries Lesions

The International Caries Classification and Management System (ICCMS), inte-

grates ICDAS scores with more extensive patient-level information for caries man-
agement. Non-cavitated enamel caries lesions are classified as initial stage decay,
62 F. B. de Araujo et al.

localized enamel breakdown and underlying dentin shadow lesions are categorized
as moderate stage decay, and cavitated dentinal caries lesions are categorized as
extensive stage decay. Although ICCMS was not yet validated for treatment pur-
poses, it recommends that active initial lesions be managed with noninvasive or
micro-invasive treatments, while active moderate lesions should be managed by
micro-invasive or invasive treatments [45]. Restorative procedures are indicated for
extensive caries lesions, and if restorative care is not possible, clinicians should
consider the Hall Technique or extraction [45]. Nevertheless, it is important to
emphasize that the mere presence of mineral loss in dentin does not indicate the
need for operative treatment. The treatment decision should be individualized and
based on the assessment of the patient’s caries activity and caries risk (e.g., sucrose
and fluoride exposure, oral hygiene habits and previous history of the disease). Due
to the multifactorial nature of the caries disease, it is important to know which fac-
tors are imbalanced and consequently lead to the development and progression of
caries lesions in each specific case. In addition, one should take into account other
factors that may influence the treatment decision, such as esthetics, chewing func-
tion, and pain sensitivity. Treatment of dental caries needs to be more comprehen-
sive than simply focusing on teeth surfaces (Figs. 6.4 and 6.5). So we elaborate here
on the logical reasoning to guide the clinical decision-making.
No treatment is necessary for sound tooth surface (ICDAS score 0). Monitoring
is needed to evaluate whether the surfaces remain caries-free over time. It is impor-
tant to emphasize, however, that patients with sound or no caries activity should
receive basic prophylaxis and information about the etiological factors of the dis-
ease and be coached on the importance of adequate oral hygiene, healthy diet, and
regular use of fluoride (fluoride toothpaste).

Occlusal lesion
management

Enamel lesions Underlying dark Cavity with

(non-cavitated/
cavitated)
shadow lesions visible dentin
Esthetics
Function
Sensitivity

Inactive Active Active Inactive

Biofilm control Biofilm control

not possible possibility

Hall
No Professional Professional Restor- Restor- No Restor-
Sealant SDF Sealant Tech- SDF Sealant SDF NRCC
intervention Fluoride Fluoride ation ation intervention ation
nique

Fig. 6.4 Treatment possibilities for the management of occlusal caries lesions (disease control is
essential for intervention success. Every patient, regardless of the clinical status of the lesion,
should be monitored)
6 The Caries Lesion: Diagnosis, Decision-Making, and Recommendations for Lesion… 63

Proximal lesion
management

Cavity with
Enamel lesions Enamel lesions visible dentin
(non-cavitated) (cavitated) (Biofilm control not
possible)

Inactive Active Inactive Active Inactive / Active

No Professional Infil- No Professional Hall

Sealant SDF Sealant SDF Restoration
intervention Fluoride trant intervention Fluoride Technique

Fig. 6.5 Treatment possibilities for the management of proximal caries lesions (disease control is
essential for intervention success. Every patient, regardless of the clinical status of the lesion,
should be monitored)

Active initial lesions, such as a first visually noticed change in enamel (ICDAS
score 1) and a distinct change in enamel when viewed wet (ICDAS score 2), can be
treated by focusing exclusively on disease control with noninvasive methods at the
patient level. However, considering the patient profile and the tooth surface, adju-
vant micro-invasive methods can be used. Regular use of fluoride toothpaste of at
least 1000 ppmF [46] and professional topical fluoride applications complemented
with professional biofilm control are noninvasive approaches [47]. When the child
is not able to self-care, the use of fluoride toothpaste twice a day in small amount is
the responsibility of parents or caregivers.
Professional prophylaxis followed by topical professional fluoride applications
(acidic gel, FFA 1.23%) in an average of four applications is indicated when caries
activity is prevalent in all quadrants. Varnishes are indicated when caries lesions are
located in specific teeth, complemented with professional biofilm control, mediated
by the visible plaque index and gingival bleeding index [47]. The use of silver
diamine fluoride (SDF) may also be an option for arresting enamel caries lesions in
primary teeth since it has been shown that the semiannual application of 38% SDF
and 5% sodium fluoride varnish had similar effectiveness [48]. A targeted approach
to dietary control should also be considered and aim to reduce sugar intakes via
food or drinks [49]. Sealants can be used for controlling initial lesions on occlusal
[50] and proximal [37] surfaces. Resin infiltrant is an alternative treatment recom-
mended only for treating non-cavitated lesions on proximal surfaces extending into
the inner half of enamel up to the outer half of the dentin [51]. The limited number
of studies evaluating outcomes, such as open cavitation, makes it unfeasible to
64 F. B. de Araujo et al.

recommend a specific management approach for initial caries lesion control in pri-
mary teeth [52].
Inactive non-cavitated enamel lesions, regardless of the surface where they are
located (occlusal or proximal), do not require any type of intervention, except for
esthetic reasons in anterior teeth.
Moderate lesions, such localized enamel breakdown in opaque or discolored
enamel (ICDAS score 3) may be treated by the noninvasive approaches mentioned
above. Most of the time, cavitated lesions provide an additional niche for biofilm
retention, and it may not be possible to remove it effectively with the bristles of the
brush. In these situations, blocking with resin sealant (Fig. 6.6) is recommended.
The treatment decision for underlying dark shadow from dentin with or without
localized enamel breakdown (ICDAS score 4) depends on the lesion’s depth. For
this, interproximal radiographic evaluation is recommended. Micro-invasive (resin
sealant or flowable resin composite) or noninvasive approaches can be recom-
mended for lesions without radiolucency at the dentin, with radiolucent image at the
enamel-dentin junction or at the outer half of the dentin. Despite the lack of evi-
dence on the sealing of underlying dark shadow from dentin lesions in permanent
teeth, previous studies have demonstrated the effectiveness of this technique for
controlling cavitated dentin caries lesions with moderate radiographic depth (up to
the outer half of dentin) [53–55], and similar results have been described for pri-
mary teeth [56]. Invasive treatment (selective carious tissue removal and adhesive
restoration) can also be indicated for treating ICDAS 4 lesions exhibiting radiolu-
cency at the outer half of the dentin. Restorative treatment is indicated for such

a b

c d e

Fig. 6.6 Proximal resin sealant, radiographic appearance (a), Microcavitated active enamel lesion
on proximal surface with pre-wedging for direct access (b), Acid etching with phosphoric acid
(Ultra-Etch™, Ultradent), adhesive system application (Scotchbond Universal, 3M Oral Care),
and immediate “drying” with microbrush, followed by light curing (c), Application of flowable
resin composite (Filtek Z350 XT, 3M Oral Care) as a proximal sealant (d), Immediate appearance (e)
6 The Caries Lesion: Diagnosis, Decision-Making, and Recommendations for Lesion… 65

lesions radiographically shown to reach the inner half of the dentin, due to the pos-
sibility of lesion progression or surface fracture resulting from lack of enamel sup-
port. Minimal intervention procedures in deep dentin will be discussed extensively
in Chap. 10. It is important to emphasize that clinical evaluation of the activity of
underlying dark shadow from dentin lesions is not possible due to visual and tactile
inaccessibility to dentin tissue (although clinical characteristics of the overlying
enamel may provide useful information). Since there are no longitudinal studies to
date evaluating the pattern of progression of underlying dark shadow from dentin
lesions, if there is radiographic evidence of the lesion, the assumption is that such
lesions may be progressing and therefore have to be arrested (by sealing or restora-
tion, depending on the radiographic depth). For severe lesions, such as distinct cav-
ity with visible dentin (ICDAS score 5) and extensive distinct cavity with visible
dentin (ICDAS score 6), the treatment decision also depends on the lesion’s depth.
One of the recommended protocols for cavities (ICDAS score 5) on occlusal sur-
faces restricted to the outer half of the dentin with a diameter of up to approximately
3 mm (extent) on primary and permanent teeth without painful symptoms or pulpal
involvement is resin sealant (Fig. 6.7) [38, 56, 57]. It is also suggested to seal cavi-
ties of up to 5 mm [57], since we have the possibility of using materials with better
mechanical properties such as flowable resin composite [58]. It should be noted that
the extent of the lesion is one of the determinant factors of treatment failure [59].
Finally, when opting for more conservative treatments, regular follow-ups are
essential to control for possible clinical failure of the sealant [54, 55] and the need
to repair the material [23]. If the decision is to perform restorative treatment,
whether by the conventional restorative approach or by atraumatic restorative treat-
ment (ART) that uses only manual instruments to access and clean the cavity [60,
61], selective carious tissue removal must be chosen [62]. Additionally, it is of para-
mount importance that the clinician performs a careful assessment of the pulpal
condition. This issue will be discussed in Chap. 10. Until recently, the possibility of
not restoring a cavitated dentin lesion was considered unacceptable. However, with
the knowledge acquired in the last decades regarding the evolution of the disease,
along with the evidence provided by clinical studies, the “sealing” of the caries
lesion presenting open cavitation with a steel crown without previous removal of the
caries tissue (Hall technique) is a possibility with proven effectiveness [40], being a
technique of easy execution and low cost that preserves the dental structure [63].
Hall technique has demonstrated lower chance of failure when compared with non-
selective removal and conventional restorations for treating cavitated but not deep
lesions in primary teeth [64]. Non-restorative cavity control (NRCC) has been rec-
ommended for primary teeth [65] and for specific cases in permanent teeth [39],
aiming to control lesion progression. In clinical practice, this approach is a more
conservative treatment option, whereby invasive procedures can be postponed or
even avoided. It can also be indicated for more specific clinical situations, such as
difficulty in patient cooperation with conventional restorative treatment, very large
and expulsive cavities in primary teeth in which a conventional restorative treatment
is highly likely to fail, short time to primary tooth exfoliation, and locations where
conventional treatment is difficult to access. However, it is of great importance to
66 F. B. de Araujo et al.

a b

c d

Fig. 6.7 Occlusal resin sealant for treating active cavitated dentin lesion (a), Radiographic
appearance at outer half of the dentin (b), Acid etching with phosphoric acid (Ultra-Etch™,
Ultradent), followed by adhesive system application (Scotchbond Universal, 3M Oral Care) (c),
Tooth appearance after application of flowable resin composite (Filtek Z350 XT, 3M Oral Care) as
sealant (d)

establish adequate communication with parents and/or caregivers, since biofilm

removal is the basis for the success of this type of therapy [39]. Based on very low
certainty of evidence, there is no significant difference in the chance of failure
between NRCC and nonselective removal and conventional restoration for non-­
deep lesions in primary teeth. Otherwise, a lower number of failures have been
observed with Hall technique than NRCC in primary teeth [64]. From an orthodon-
tic standpoint, the treatment protocol that consists of cleaning medium- and large-­
sized occlusal and proximal cavities in primary teeth that are left open with
toothbrush and fluoride toothpaste and restoring small-sized cavities with the ART
method does not differ significantly from the traditional amalgam and ART restor-
ative protocols with respect to intra-arch distances and malocclusion [66]. The use
6 The Caries Lesion: Diagnosis, Decision-Making, and Recommendations for Lesion… 67

of SDF to control cavitated dentin lesions has also been proposed, especially for
primary teeth [67]. It is a cariostatic agent, which promotes the remineralization of
the dental structure, protecting the collagen fibers, besides having an antibacterial
effect. Scientific evidence suggests that SDF arrests dentinal caries lesions in pri-
mary teeth better than treatments such as fluoride varnish and ART restorations
[68]. It can be found in different concentrations, but 38% SDF has been shown to be
more effective than 12% SDF for arresting active cavitated caries lesions in primary
teeth [69]. The application of the SDF solution is easy, less costly [70], and painless.
There is no need to remove carious dental tissues before the SDF application, which
simplifies the treatment procedure and reduces patient discomfort. Thus, SDF can
be a promising strategy to control dental caries, mainly in very young and difficult-­
to-­manage children (see Chap. 8).

6.6 Concluding Remarks

• The understanding that dental caries and caries lesions are not synonymous is of
fundamental importance for the control of the disease and management of its
sequelae. The treatment process starts with an accurate diagnosis that takes into
account the caries activity of the individual.
• The clinical approach to caries disease and its consequences should be based on
the principles of the minimally invasive dentistry, always adopting noninvasive
treatment measures for caries lesions (brushing with fluoride toothpaste of at
least 1100 ppm, reducing the consumption of sugars, and supplementing with
professional fluoride).
• For treatment of non-cavitated active occlusal caries lesions (ICDAS score 1 and
score 2), cavitated enamel lesions (ICDAS score 3), or underlying dark shadow
from dentin (ICDAS score 4) reaching the outer half of the dentin, micro-­invasive
approach (sealing) is recommended.
• For proximal non-cavitated caries lesions (ICDAS score 1 and score 2), noninva-
sive or micro-invasive treatment is suggested.
• When there is doubt about the presence of cavitation on the proximal surface in
the radiographic image with radiolucency at dentin (ICDAS score 4), the clini-
cian should validate it by temporarily separating the teeth for up to 48 h. In the
presence of cavitation, if the clinician decides to use micro-invasive approach, it
is imperative to avoid retentive interfaces for oral biofilm accumulation, to reduce
the risk of adjacent caries lesions.
• In lesions with distinct cavity with visible dentin (ICDAS score 5), cavities on
occlusal surfaces located on the outer half of the dentin with a diameter of up to
approximately 3 mm (extent), a micro-invasive approach can also be used.
• When invasive intervention is necessary for dentin lesions, selective removal of
caries tissue should be the method of choice, since nonselective carious tissue
removal is contraindicated (overtreatment).
68 F. B. de Araujo et al.

• The decision for minimally invasive restorative techniques has the advantages of
low cost, shorter clinical time, and greater patient compliance. These restorative
techniques are strongly recommended as they preserve healthy dental tissue
throughout the patient’s life.

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Pulp Response to Clinical Procedures
and Dental Materials 7
Josimeri Hebling , Igor Paulino Mendes-Soares ,
Rafael Antonio de Oliveira Ribeiro ,
and Carlos Alberto de Souza Costa

Contents
7.1 Introduction 74
7.2 Concepts About In Vitro Animal and Usage/Clinical Tests 75
7.2.1 Resin Infiltration Systems for Treatment of Enamel White Spot-Like Lesions 76
7.2.2 Silver Diamine Fluoride (SDF) 79
7.2.3 Tooth Whitening Agents 82
7.2.4 Bonding Agents, Glass Ionomer, and Calcium Silicate Cements 86
 eferences
R 92

J. Hebling
Department of Morphology, Pediatric Dentistry and Orthodontics, School of Dentistry, São
Paulo State University (UNESP), Araraquara, SP, Brazil
e-mail: [email protected]
I. P. Mendes-Soares · R. A. de Oliveira Ribeiro
Department of Dental Materials and Prosthodontics, School of Dentistry, São Paulo State
University (UNESP), Araraquara, SP, Brazil
e-mail: [email protected]; [email protected]
C. A. de Souza Costa (*)
Department of Physiology and Pathology, School of Dentistry, São Paulo State University
(UNESP), Araraquara, SP, Brazil
e-mail: [email protected]

© The Author(s), under exclusive license to Springer Nature Switzerland AG 2023 73

A. B. Fuks et al. (eds.), Contemporary Endodontics for Children and
Adolescents, https://doi.org/10.1007/978-3-031-23980-9_7
74 J. Hebling et al.

7.1 Introduction

For decades, bacteria and their products were considered as the main responsible for
pulpal breakdown. In that time, it was stated that rather than dental materials and
their components, the presence of caries, cracks, and fractures in the tooth structures
and open gaps at tooth/restoration interface, which provided pathways for microor-
ganisms and their toxins to diffuse toward the pulp, were the main factors capable
of causing damage to this specialized connective tissue (Fig. 7.1a–c).

b
AF

a
ID

TD D IF

AF
ID c
M
AD
TD

D
P TD
TD

Fig. 7.1 (a) Very deep caries lesion in a primary molar that resulted in pulp exposure. D dentin; P
pulp; TD tertiary dentin; M microabscess; ID infected dentin; AD affected dentin. Masson’s tri-
chrome, 64×. (b) Interface between infected and affected dentin. While IF dentin is totally disor-
ganized, the tubular structure of AD is preserved with bacteria displacing through it. Brown and
Breann technique, 125×. (c) Microorganisms inside dentinal tubules (arrows). Transmission elec-
tron microscopy—TEM
7 Pulp Response to Clinical Procedures and Dental Materials 75

7.2 Concepts About In Vitro Animal and Usage/Clinical Tests

Based upon a sequence of laboratory animal and clinical studies performed in the
last 30 years, researchers have demonstrated that some dental materials and their
components, under specific conditions of use and application, may diffuse across
enamel and dentin to cause since a slight tissue inflammation to pulp necrosis. Most
of basic investigations performed in this field has focused on the knowledges about
molecular biology and mechanisms involved in the process of repair and regenera-
tion of the dentin-pulp complex submitted to various types of aggressions, such as
those caused by microorganism contamination, trauma, toxicity of dental materials,
and thermal injuries. This has appeared to become more evident and possible by
means of the recent advancements in knowledge of the dentin-pulp complex, func-
tions and activities of pulp stem cells, as well as the possibility of developing bio-
products that mimic the extracellular matrix, in which signaling molecules can be
added. However, extrapolating this body of knowledge and encouraging scientific
data obtained from laboratory and in vivo studies performed in animals to clinical
situations has been the most dramatic challenge.
Overall, efforts have been done by researchers to establish dental materials and
clinical procedures safe for patients and clinicians as well. In this way, the guideline
of international organizations, such as the US Food and Drug Administration (FDA)
and International Organization of Standardization (ISO), which determine the per-
formance of rational in vitro trials, in animals and usage/clinical tests, must be fol-
lowed, and contemporary protocols adapted to present day should be pondered and
discussed. Taking into consideration this topic, the main purpose of this chapter is
to provide a general and critical view of the relations that permeate the interaction
between dental materials and the dentin-pulp complex, as well as establish possi-
bilities of developing new biocompatible products and safe strategies of use capable
of benefiting clinicians and patients.
Before discussing the cytotoxic effects and biocompatibility of dental materials,
some concepts about in vitro, in animals and usage/clinical tests should be pre-
sented. Firstly, we need be aware that the biological effects of dental materials can
be evaluated at different research levels, from laboratory to clinical trials. Cell cul-
ture assay using in vitro pulp devices is a laboratory methodology that seeks to
simulate the role of dentin as barrier to the diffusion of dental material components
and as a protein reservoir (Figs. 7.2 and 7.3).
76 J. Hebling et al.

b c d e

Fig. 7.2 Sequence of procedures to obtain dentin discs. (a) Sound third human molars selected;
(b) after attaching the tooth on a wooden base, the first cut is carried out about 2 mm before the
cement-enamel junction; (c) second cut 0.5 mm apart from the first cut; (d) intact dentin discs
selected to be used for indirect test of cytotoxicity; (e) dentin disc being adapted to the in vitro
pulp chamber

Concerning the in vitro protocols widely used in laboratory, they are considered
as sophisticated tests that can assess nearly any aspect of cell function and metabo-
lism, including gene expression, signaling activation, cell cycle and division, inflam-
matory activation, protein expression, oxidative stress, and many others. Some
advantages of the in vitro tests are control of variables, no or minimal ethical con-
cerns, standardization, detailed cell response, reproducible, less expensive, and
faster. On the other hand, the main disadvantage of such laboratory tests is that
irrespective of the methodology used, the results obtained should be carefully inter-
preted, and these data cannot be directly transposed to clinical conditions.

7.2.1 Resin Infiltration Systems for Treatment of Enamel White

Spot-Like Lesions

Resin infiltration is a micro-invasive treatment for non-cavitated caries management

[1]. In this clinical procedure, diffusion barrier is established within the lesion body
by using a low-viscosity resin-based material that is capable of blocking cariogenic
acid diffusion, arresting the advancement of demineralization and caries progres-
sion [2, 3]. It was already shown that the use of resinous infiltrants can mask the
opaque look of lesions due to the refractive index of the infiltrant (approximately
1.52) that is similar to that of hydroxyapatite (1.62) [4]. Therefore, after infiltrating
the intercrystalline spaces with the low-viscosity resin, the difference in color
between the enamel and infiltrated lesion often becomes clinically imperceptible
[5]. In this way, resin infiltration systems have been widely employed for esthetic
7 Pulp Response to Clinical Procedures and Dental Materials 77

a b

c d

e f

Fig. 7.3 Sequence of application of a etch-and-rinse bonding agent on the occlusal surface of a
dentin disc. To simulate clinical conditions, pulp cells were previously seeded on the pulpal surface
of the disc. (a) Sterilized in vitro pulp device inserted in a well of a 24-well culture plate with the
occlusal side of the dentin disc facing up; (b) phosphoric acid application on dentin; (c) acidic
agent carefully rinsed with ultrapure water and simultaneous aspiration of the water to prevent
overflow; (d) surface drying with absorbent paper; (e) bonding agent application; (f) bonding agent
photoactivation

improvement of developmental defects of enamel, such as fluorosis, traumatic

hypocalcification, and molar-incisor hypomineralization [4] (Fig. 7.4).
Overall, the resin infiltration therapy is characterized by a three-step procedure
that follows a sequence of application. Firstly, a hydrochloric acid (HCl) agent is
used to condition the selected enamel. After rinsing the etched enamel, an ethanol-­
based drying agent is employed to promote the dehydration of the substrate and
improve its wettability. Finally, a low-viscosity resin-based infiltrant containing tri-
ethylene glycol dimethacrylate (TEGDMA) is applied and then light-cured
(Fig. 7.4). Despite resin infiltrant systems being recommended to be used in specific
clinical situations, such as to treat non-cavitated lesions that involve the external
78 J. Hebling et al.

Fig. 7.4 Sequence of a resin infiltration system being used for treatment of enamel white spot
caries-like lesion on the mesial surface of a permanent first molar. Courtesy of Prof. Dr. Diego
Girotto Bussaneli, Prof. Dr. Manuel Restrepo Restrepo, and Prof. Dr. Rita de Cássia Loiola Cordeiro

third of dentin, their potential adverse effects to the dentin-pulp complex have been
little investigated. Even when applied on enamel, it is not yet clear whether
TEGDMA released from the products may diffuse through enamel and dentin to
reach the pulp cells in toxic concentrations. In a current study, the authors assessed
the trans-enamel and trans-dentinal response of odontoblast-like cells and human
dental pulp cells after infiltrating enamel white spot-like lesions with the resin infil-
tration system Icon by DMG (Germany). It was shown that in spite of the buffer
action of enamel and dentin, the application of the acidic agent (HCl) on enamel
reduced by 70% the viability of pulp cells and upregulated their gene expression of
the inflammatory cytokines IL-1β and TNF-α. The authors reported that such pulp
cells also had reduced production of total protein, activity of alkaline phosphatase,
and formation of mineralized nodules, which are directly related to dentin-pulp
repair/regeneration. Based on these data, the authors presumed that HCl was able to
diffuse through enamel and dentin to reach the cells in highly toxic concentrations.
However, the reduction of cell viability after application of the low-viscosity
7 Pulp Response to Clinical Procedures and Dental Materials 79

resin-­based infiltrant to unetched enamel was lower than 30%, which is considered
as a non-toxic effect according to international standards [6, 7]. This result seems to
indicate that TEGDMA released from the infiltrant agent is not capable of diffusing
through the enamel lesion unless the hyper-mineralized surface is removed and
interprismatic diffusion channels are created. Another possibility is that the amount
of uncured TEGDMA diffused through enamel and dentin was not enough to cause
toxic effects to pulp cells. When the resin-based infiltrant was applied to the HCl-­
etched enamel, the cell’s viability reduced by 40%. Interestingly, in this condition,
the adverse effects on pulp cells were lower in comparison with HCl agent applied
alone to enamel. This finding may be related to the reaction of residual HCl with the
monomers present in the resin-based infiltrant. TEGDMA molecules contain ester
groups [–C(〓O)O–C–], which may undergo hydrolysis by acid catalysis [8].
Therefore, the possible interaction of the acid with the methacrylate esters may
justify how infiltrant reduced the toxicity of etching agent by consuming the disso-
ciated HCl and reducing the content of unreacted HCl available for trans-­
amelodentinal diffusion. Overall, the use of Icon as resin infiltration therapy
adversely influenced the metabolic activity of pulp cells. The detrimental side
effects were mainly related to the use of HCl. Of course, clinical extrapolations of
data obtained from laboratory studies are limited, and further clinical trials as well
as investigations using longer periods of evaluation are still needed to determine
whether the effects of managing enamel caries lesions with resin infiltration sys-
tems are transitory. However, we should be aware that the application of resin infil-
tration strategies for managing non-cavitated caries lesions, especially if the external
third of the dentin is involved, need to be carefully performed.

7.2.2 Silver Diamine Fluoride (SDF)

Among clinical procedures widely used to prevent caries progression, there are
those related to minimum intervention, with goals to maintain the integrity of dental
tissues, prevent pulp exposure occurrence, and, when necessary, improve the behav-
ior of patients. For example, the atraumatic restorative treatment (ART) and the
indirect pulp capping therapy are both considered minimum intervention approaches
that employ procedures of selective caries removal in primary and permanent teeth
[9, 10] (Fig. 7.5a–c).
Another clinical procedure included in this approach is the application of silver
diamine fluoride (SDF) as desensitizing and cariostatic agent [11–13]. Based on its
low cost, SDF application has been indicated for blocking caries evolution [14] and
preventing radicular caries occurrence in high caries-risk patients [15].
SDF is a salt [Ag(NH3)2F] that contains fluoride ions (F−) and silver (Ag2+),
which give rise to ammonia complexes (NH3). When dissolved in water, a highly
alkaline and colorless solution is generated [12]. It has been shown that SDH has
three specific properties that make it effective to control caries lesion evolution: (1)
antibacterial effect, (2) remineralization action, and (3) antiproteolytic activity. All
these properties are related with the bioavailability of F− and Ag2+ [13].
80 J. Hebling et al.

b
a ID

ID
D ID
AD ID
AD

TD
AD

c
IP
D ID
TD

Fig. 7.5 (a) Primary molar with very deep caries lesion. D dentin; IP inflamed pulp; TD tertiary
dentin; ID infected dentin; AD affected dentin. H/E, 64×. (b) Interface between infected and
affected dentin. In the ID zone, wide zones of dentin degradation with high content of bacteria are
observed (arrows). Brown & Brenn technique, 125×. (c) Note that subjacent to the bacteria-­
degraded ID, a number of micro-organisms are starting diffusion through dentinal tubules (arrows).
Brown & Brenn technique, 180×

Several studies have shown that F− plays a main role in the process of hard dental
tissue remineralization [16, 17]. Additionally, F− has antimicrobial effects on micro-
organisms present in cariogenic biofilm [18]. The chemical reaction between SDF
and hydroxyapatite gives rise to silver phosphate and calcium fluoride, which
increase the local pH; calcium fluoride also acts as Ca+ and F− reservoir, improving
the tissue remineralization process [11, 12, 19]. SDF can also deposit mineral along
150 μm of demineralized dentin. The high concentration of calcium and phosphorus
deposited by SDF inside dentinal tubules is capable of blocking, even partially, the
caries lesion evolution, preventing the occurrence of pulp exposure [20–22].
Previous studies showed that a solution of 38% SDF, which contains 44.800 ppm of
F−, is effective to avoid tooth sensitivity and reduce caries lesion progression
[14, 23].
Researchers have shown that SDF has potential to inhibit dentinal endopepti-
dases, protecting local collagen against enzyme-mediated tissue degradation [11,
23]. The inhibitory activity of SDF on metalloproteinases (MMP-2, -8 e -9) is higher
than that caused by sodium fluoride (NaF) and silver nitrate (AgNO3) [24]. The
exact mechanism by which such dentin MMPs are inactivated by SDF still remains
nuclear. However, based on the fact that dentin MMPs cause degradation of dentin
collagen in a neutral pH environment, one may suggest that the high pH of SDF
solutions (about 12–13) interferes with these enzymes’ activity.
7 Pulp Response to Clinical Procedures and Dental Materials 81

a b

Fig. 7.6 (a) Clinical situation in which caries lesions are present in a number of primary teeth. (b)
One week after performing the topic application of potassium iodide solution, the caries tissue was
darkened by impregnation of metallic silver particles generated by oxidation of silver ions released
from the cariostatic agent. Courtesy of Dr. Kasandra Verónica Yupanqui-Barrios

When included in the SDF solution, silver ion assumes a remarkable role against
biofilm formation, since this specific chemical compound prevents aggregation of
Streptococcus, Actinomycetes, and Lactobacillus, which are responsible for the
beginning of the caries lesion. Silver ion react with the microorganism’s membrane
to cause its disruption; in this way, the microorganism’s metabolic activity is inhib-
ited [11, 12, 25]. However, it is known that silver ions are oxidated to generate
metallic silver, which causes darkening of caries tissue. Therefore, chromatic teeth
change seems to be the main clinical adverse effect caused by topic application of
SDF on dentin (Fig. 7.6a, b). Despite the darkening of the caries lesion in dentin, the
impermeable layer formed on the tissue stabilizes the caries progression [20–22]. It
has been demonstrated that the application of potassium iodide (IK) on the SDF-­
darkened caries lesion may improve the esthetic outcome [26]. This may be
explained by the fact that silver ions from SDF interact with IK to form a local white
compound, which prevents the darkening of the SDF-treated caries lesion without
affecting the positive results caused by this therapy [25, 27].
Only a few data are actually available concerning the cytotoxicity and biocom-
patibility of SDF and their components to the dentin-pulp complex. On the other
hand, after applying SDF 38% solution on caries lesion in dentin, researchers dem-
onstrated that silver ions were present further into the subjacent dentinal tubules
[22]. The authors showed that the silver particles released from SDF displaced by
around 744.7 μm (±448.7 μm) in dentin. Despite the presence of silver particles
inside dentinal tubules, no intense pulp inflammation was observed at 6-month
period after using SDF to treat caries lesions present in human teeth [21]. However,
it was shown that silver ions were capable of diffusing even 2.490 μm further into
dentinal tubules. Therefore, depending on the depth of caries lesion, SDF therapy
may allow intense inward dentinal silver ion movement that may reach the pulp
chamber in concentrations high enough to cause intense cytotoxic effects. In a pre-
vious study, researchers reported that SDF causes severe and persistent damage to
82 J. Hebling et al.

human gingival fibroblasts [28]. Therefore, in order to determine how safe to dentin-­
pulp complex is the treatment of caries lesions with SDF, laboratory investigations
and clinical trials still are needed. In a current study conducted by our research
group, standardized dentin discs (0.4 mm thick) were obtained from human molars.
These discs were individually adapted into artificial pulp chambers. On the pulpal
surface of the discs, odontoblast-like cells were seeded to mimic the odontoblast
layer that is physiologically underlying dentin in mammalian (human) teeth. On the
occlusal surface of these thin discs, caries lesions were created to simulate a clinical
condition of very deep caries in dentin, which was submitted to therapy with Riva
Star (SDI, Bayswater, VIC, Australia). Then, after treating the caries lesions with
silver diamine fluoride solution (SDF), iodine potassium solution (IK), or SDF fol-
lowed by IK (SDF + IK) (n = 8), the pulp cells were assessed concerning their via-
bility. Considering the non-treated discs as 100% cells viability (control), SDF
application on caries lesions decreased the viability of the pulp cells by 46%. On the
other hand, IK and SDF + IK reduced cell viability by only 13% and 3%, respec-
tively. These data indicate the positive association of SDF and IK against the trans-
dentinal cytotoxicity of SDF therapy. We all must be aware about the limitations of
results of in vitro investigations. However, taking into account the exciting data
obtained in this study of cytotoxicity and considering the fact that clinical esthetic
outcome can be improved when IK is added to SDF solution, it seems reasonable
using these combined components as recommended by the manufacturer (detailed
clinical use is presented in Chap. 8).

7.2.3 Tooth Whitening Agents

Tooth whitening is actually the most popular esthetic treatment since it uses a sim-
ple and noninvasive clinical technique. The ease of performing the in-office tooth
whitening therapy to obtain a relatively fast esthetic results seems to be the main
benefit that has made the use of this professional whitening technique the procedure
that is still preferred by patients and clinicians. On the other hand, several laboratory
studies have shown that whitening gels containing high concentrations of hydrogen
peroxide (H2O2), such as those used for in-office tooth whitening, induce intense
oxidative stress and severe damage to pulp cells [29, 30]. This undesirable adverse
effect has been related to the ability of H2O2 to disrupt the mineral structure of
enamel, which allows trans-amelodentinal diffusion of this toxic reactive oxygen-­
derived specie (ROS) toward the pulp chamber [31, 32]. The toxicity caused by
H2O2 to pulp cells seems to be related with post-whitening tooth sensitivity, which
has been reported to have more than 70% of patients submitted to this professional
esthetic therapy. Recent studies demonstrated that the intensity of the toxic effects
of H2O2 to pulp cells is inversely proportional to the thickness of tooth enamel/den-
tin and directly related to concentration and time of application of the whitening gel
on teeth [33]. Therefore, the higher the concentration of H2O2 in the whitening gel
and the longer the time of contact of the product with enamel, the more intense will
be the toxicity of the esthetic procedure to pulp cells [34, 35]. Based on these data,
7 Pulp Response to Clinical Procedures and Dental Materials 83

one may suggest that application of in-office whitening gels with 35–40% H2O2 for
periods of 30–45 min on incisors represents the most dramatic challenge for the
dentin-pulp complex. In the last few years, researchers performed clinical investiga-
tions, in which in-office tooth whitening was carried out in sound premolars and
lower incisors of patients that had their teeth extracted for orthodontic reasons. In
these studies, the authors showed that only a slight or no pulp damage occurred in
premolars after application of high-concentrated whitening gels for 30–45 min on
their buccal surface [36–38]. Almost all premolars submitted to these in-office whit-
ening treatments exhibited normal pulp tissue, and the patients did not report any
post-whitening sensitivity. On the other hand, the same professional therapies
applied to incisors caused partial necrosis of the coronary pulp associated with local
inflammation even two days after concluding the treatment. In these cases, almost
all patients reported post-whitening tooth sensitivity (Figs. 7.7 and 7.8a, b).

Fig. 7.7 Short magnification of the pulp horn (P) of a human premolar submitted to conventional
in-­office whitening therapy. The dentin-pulp complex is histologically normal. Below the intact
odontoblast layer, which is lining the dentin substrate (D), one can see blood vessels and a number
of pulp cells immersed in extracellular matrix. H/E, 64×

a b
D
D

P TD
NP

Fig. 7.8 (a) Pulp horn of human incisor submitted to conventional in-office whitening therapy. No
cells, blood vessels, and extracellular matrix can be observed. Note that this area of the coronary
pulp exhibits necrosis (NP). H/E; 96×. (b). Radicular pulp of the human incisor submitted to con-
ventional in-office whitening therapy. Intense deposition of tertiary dentin (TD) is observed
between the tubular primary dentin and the pulp, which exhibits a number of small dilated and
congested blood vessels. H/E, 210×
84 J. Hebling et al.

Based on the results of these clinical studies, in which the whitened teeth were
extracted and processed for microscopic analysis of the dentin-pulp complex
response against the esthetic therapies, one could consider that the degree of the post-
whitening sensitivity was directly related with the intensity of the dentin-pulp dam-
age. In another clinical study, lower incisors from young patients scheduled for
extraction were subjected or not to three 15-min applications of a whitening gel with
35% H2O2 [39]. Two days thereafter, bleaching effectiveness (according to a value-
oriented shade guide) was evaluated, and histological analysis of pulp tissue was
performed under light microscope. Immediately and two days after the professional
procedure, post-whitening tooth sensitivity experience was recorded. Despite the
significant color improvement observed after concluding the esthetic treatments,
teeth of all patients experienced post-whitening sensitivity and exhibited significant
pulp alterations, characterized by areas of superficial necrosis associated with mild
inflammatory reactions. These data were compared to those obtained from elderly
patients who also had their lower incisors submitted to the same whitening therapy.
Overall, partial pulp necrosis occurred in about 60% of old bleached teeth in com-
parison with 100% of young teeth. The authors concluded that regardless of the age
of patients, the in-office whitening therapy applied to lower incisors causes intense
pulp damage, which is related to tooth sensitivity. On the other hand, considering the
data of this clinical study, one can suggest that pulp damage is prevalent and more
severe in young teeth, which present larger pulp chamber as well as enamel and den-
tin thinner than old teeth.
Taking into consideration the adverse effects caused by the conventional in-­office
whitening therapy currently used in dentistry [40], several researchers have evaluated
some strategies to minimize them, such as the use of desensitizing agents applied
topically or incorporated into the whitening gels. Prescription of analgesics or anti-
inflammatories [41] and the application of bleaching gels with low H2O2 concentra-
tions [42, 43] have also been assessed and clinically recommended. However, the
first two strategies do not prevent H2O2 diffusion through the enamel/dentin and con-
sequent pulp damages. Using gels with low H2O2 concentrations limits the chromatic
change of dental tissues, which makes this treatment unfeasible because it requires
several clinical sessions to promote satisfactory whitening outcomes.
Nowadays, the association between the application of ozone (O3) and whitening
gels has shown an attractive strategy to improve the esthetic results and reduce post-­
whitening tooth sensitivity [44]. Nevertheless, no clinical or laboratory studies have
determined the possible toxic effects of this innovative technique to pulp cells.
Based upon the knowledge about the mechanisms involved in whitening the miner-
alized tooth tissues, it would be interesting that all H2O2 present in high-­concentrated
whitening gels could interact with the chromophores in order to prevent residual
H2O2 from reaching the pulp tissue. However, the high concentration of H2O2 in gels
frequently used for professional tooth whitening and low oxidation capacity of this
toxic molecule allow residual H2O2 to remain in dentin (free-H2O2) to diffuse
quickly toward the pulp chamber. Therefore, other exciting approach that has
7 Pulp Response to Clinical Procedures and Dental Materials 85

actually been widely investigated is incorporating catalyzing agents in whitening

gels with variable concentrations, which may result in a similar esthetic efficacy to
that obtained with conventional in-office tooth whitening [45, 46]. This strategy
basically has the objective of accelerating the decomposition of residual H2O2 pres-
ent in the whitening gels by the catalyzing agent, which induces the generation of
other highly reactive oxygen species (ROS) with an extremely short half-life [31].
Consequently, after interacting and causing very fast degradation of the chromo-
phores present in darkened dental tissues, the new ROS generated are eliminated,
reducing the possibility of trans-amelodentinal toxic effects to pulp cells [47, 48].
To make this innovative strategy viable, researchers started evaluating the use of
transition metals and enzymes with catalyst potential, associated or not with the
photocatalysis of whitening gels with LED at a visible violet wavelength (V-LED)
[45]. The use of V-LED for tooth whitening has also been justified by the fact that
the V-LED wavelength (405–410 nm) corresponds to the absorption peak of chro-
mophores. Considering that these colored organic molecules are highly reactive, it
is assumed that the presence of violet light could trigger the instability and rupture
of chemical bonds, promoting the bleaching effect by a photophysical process.
Based on the potential benefits of the chemical catalysis and photocatalysis of H2O2
to professional tooth whitening, our research group evaluated the influence of the
association of manganese oxide (MnO2) and V-LED on the esthetic efficacy and
trans-amelodentinal cytotoxicity of whitening gels with 6% and 10% H2O2. In this
specific investigation, we showed that associating LEDv+MnO2 in whitening proce-
dures with gels containing such low H2O2 concentrations results in esthetic outcome
similar to that obtained with the conventional in-office tooth whitening, in which a
gel with 35% H2O2 was used. Compared to professional whitening, we demon-
strated that the lowest indices of trans-amelodentinal H2O2 diffusion occurred when
both low-concentrated whitening gels containing MnO2 were irradiated with
V-LED. Taking into consideration this fact, we observed that the chemical catalysis
of the H2O2 present in the whitening gels with MnO2 and their photocatalysis with
V-LED caused only a discrete toxicity to pulp cells. On the other hand, the conven-
tional in-office whitening therapy caused an intense oxidative stress and damage to
pulp cells. Recovering the enamel with a polymeric catalyst primer before applying
the whitening gel, which is then submitted to V-LED photocatalysis, is another
approach that has shown excellent results. Despite these exciting findings that have
established more effective and biocompatible whitening approaches to dentin-pulp
complex, further investigations are still needed. However, all the innovative strate-
gies presented here have driven the future of tooth whitening therapies, especially
for professional treatments. Thus, taking into consideration the scientific data cur-
rently available, we must be aware that the conventional in-office whitening thera-
pies widely used nowadays are extremely toxic to pulp cells and may cause
post-whitening tooth discomfort to patients. Additionally, one should pay attention
to the fact that pulp damage caused by these professional whitening therapies seems
to be more intense in teeth of young patients.
86 J. Hebling et al.

7.2.4 Bonding Agents, Glass Ionomer, and Calcium

Silicate Cements

For several decades, the development of adhesive dental materials has revolution-
ized many aspects of restorative and preventive dentistry, in such way that proce-
dures toward cavity preparations were revisited in order to establish the successful
minimal-invasive dentistry. The clinical use of adhesive materials improved the
esthetic outcomes and reduced microleakage at the restorative material-tooth inter-
face, decreasing postoperative sensitivity, marginal staining, and consequently sec-
ondary caries. Bonding agents, which made the resin dental substrate interaction
achievable, are solutions of resin monomers that contain hydrophilic and hydropho-
bic groups as well as curing initiators, inhibitors or stabilizers, solvents, and, in
some cases, inorganic fillers in their composition. Disregarding the clinical tech-
nique of application of these resin-based dental materials, they were developed spe-
cially to bond enamel, dentin, amalgam, metal, and porcelain. The important
properties of bonding agents have given clinicians the option of using them for vari-
ous dental treatments and application procedures. Beside allowing repair of deterio-
rated or deboned restorations, the use of bonding agents improves distribution of
functional stress at tooth structure and restorative materials in such way that the
weakened tooth structure is protected and reinforced. Bonding agents may be
applied directly on smear layer, by dissolving it or incorporating it into the bonding
process. These resinous materials may also be applied directly on dentin; in this
case, the smear layer is previously removed from dentin by acid etching. Different
chemical compositions of bonding agents and their variable sequence of application
on dentin substrate have given rise to diverse resin-dentin interface features and
shear bond strength values, as well as influenced the hybrid layer degradation with
time. Bonding agents applied on dentin result in hybrid layer of variable thicknesses
and short or long resin tags formation into dentinal tubules that frequently are
related with displacement of resin components through dentinal tubules.
Several studies have shown that resin monomers widely found in bonding agents,
such as HEMA and TEG-DMA, have defined toxicity to pulp cells [49, 50]. Therefore,
taking into consideration the fact that when resins are light-cured, only 55–60% of the
monomers react, researchers demonstrated that transdentinal inward diffusion of
uncured monomers occurs; these phenomena are inversely proportional to the remain-
ing dentin thickness (RDT) between the cavity floor and pulp tissue. In a clinical
study, the authors applied an etch-and-rinse bonding agent in deep cavities prepared
in premolars indicated to be extracted for orthodontic reason [51]. One month after
concluding the adhesive restorations, the microscopic analysis of the dentin-pulp
response against the clinical procedures was carried out. The authors showed that
when the RDT was thinner than 300 μm, inflammation and disorganization of pulp
tissue occurred. These histological findings were related to long resin tag formation
and resin monomer diffusion through dentinal tubules (Figs. 7.9a–c and 7.10).
When the cavity floor was lined with a biocompatible dental material (hard-­
setting calcium hydroxide cement) before adhesive restoration of the cavities, no
pulp damage was observed. It was also demonstrated that disregarding the intensity
7 Pulp Response to Clinical Procedures and Dental Materials 87

Fig. 7.9 (a) Class V cavity prepared in human tooth. The blue lines represent the dentinal tubules
away from the cavity floor to the pulp. C cavity; D dentin; P pulp; RDT remaining dentin thickness
<300 μm. H/E, 32×. (b) High magnification of the area selected in (a). The monolayer of odonto-
blasts is preserved (arrows). The subjacent pulp tissue exhibits normal histological characteristics.
Masson’s trichrome, 125×. (c) High magnification of the area selected in (a). Note that the odon-
toblast layer is completely disrupted and some cells aspirated into dentinal tubules. The subjacent
pulp tissue is disorganized and presents inflammatory mononuclear cells. Masson’s trichrome, 125×

of the damage presented by the pulp tissue, all patients did not claim any postopera-
tive tooth sensitivity. In another similar study, researchers applied a self-etching
bonding agent in deep cavities prepared in human premolars [51, 52]. The authors
observed lower and shorter formation of resin tags, as well as lighter inward dis-
placement of uncured resin globules through dentinal tubules in comparison with
the etch-and-rinse bonding agent. However, the amount of resin components that
reached the pulp was enough to cause disruption of the odontoblast layer, inflamma-
tory response, and local proliferation/dilatation of blood vessels. When bonding
agents were applied on human pulps mechanically exposed [52], the resinous mate-
rial elicited a chronic inflammatory pulp reaction mediated by macrophages and
giant cells, which appeared engulfing particles of uncured resin displaced into the
88 J. Hebling et al.

Fig. 7.10 This image

shows a number of uncured
resin globules (arrows)
displaced into dentinal
tubules. DT dentinal
tubule; ID intertubular
dentin. MEV

a b

D
C
PE

Fig. 7.11 (a) After very deep cavity preparation, the pulp tissue was carefully exposed, acid
etched, and then capped with a boning agent. C cavity; D dentin; PE pulp exposure; Arrows
uncured resin released from the bonding agent. Masson’s trichrome, 32×. (b) Bonding agent com-
ponents displaced into the pulp triggered an intense inflammatory response at distance of the
pulpal wound. Note that the inflammatory reaction is characterized by a number of mononuclear
cells, degradation of extracellular matrix, and proliferation of dilated and congested blood vessels
(arrows). Masson’s trichrome, 210×

pulp (Fig. 7.11). This persistent tissue inflammation that did not allow odontoblast-­
like cell differentiation and complete dentin-pulp regeneration at the pulp exposure
site even 300 days after the clinical procedure resulted in inner-dentin resorption.
On the other hand, when calcium hydroxide was used as capping agent, hard barrier
formation was deposited by new differentiated odontoblast-like cells (Fig. 7.12).
7 Pulp Response to Clinical Procedures and Dental Materials 89

a b
TD

CH HB

TD
P
P

Fig. 7.12 (a) Calcium hydroxide (CH) applied on a pulp exposure performed in human tooth,
which was extracted after a few days. Note the deposition of tertiary dentin (TD) and the partial
formation of hard barrier (arrows) adjacent to the capping agent. H/E, 32×. (b) With time, a thick
defined hard barrier (HB) is formed at the pulp exposure site. Note the new layer of differentiated
odontoblast-like cells underlying the HB. The subjacent pulp tissue (P) exhibits histological char-
acteristics of normality. H/E, 125×

A sequence of clinical/histopathologic studies performed in human teeth, in

which different bonding agents were applied in very deep cavities or used as cap-
ping agents, demonstrated similar disastrous pulp results. On the other hand,
when the cavity floor was lined with hard-setting calcium hydroxide cements
(CHC) or different formulations of glass-ionomer cements (GIC) before proceed-
ing the adhesive restoration, mild or no pulp damage was observed [53–57]. These
clinical/histopathologic studies also performed in human teeth demonstrated that
most of these cements can be recommended for clinical situations in which a layer
of sound or affected dentin remains between the cavity floor and the pulp
(Fig. 7.13).
In a few years ago, researchers applied two resin-modified GICs – Vitremer and
Vitrebond on the floor of deep cavities prepared in human teeth [55]. However,
before using Vitremer, the dentin substrate was pretreated with a primer (polyacrylic
acid plus 2-hydroxyethyl methacrylate) such as recommended by the manufacturer.
Teeth were extracted after 7 or 30 days and processed for microscopic evaluation.
The authors observed that Vitremer specimens exhibited diffusion of uncured mono-
mers across dentinal tubules associated with damage to pulp cells and inner resorp-
tion of dentin. On the other hand, no pulp damage was observed for Vitrebond
specimens. The notable biocompatibility of the conventional powder/liquid form of
Vitrebond was also demonstrated in several other studies performed in human teeth.
Conversely, in spite of being considered biocompatible, the paste/liquid formulation
of this cement (Vitrebond Plus Light Cure Glass Ionomer Liner/Base), which was
developed and introduced to the market in convenient dispensing “clicker” device
with the aim of facilitating handling and shortening the clinical time, caused more
damage to the pulp than the conventional version [54]. In another study, researchers
assessed the response of human pulps after using a conventional GIC (Riva
90 J. Hebling et al.

Fig. 7.13 Sequence of adhesive restoration of a cavity following selective caries removal. After
lining the cavity floor (affected dentin) with the resin-modified glass-ionomer cement Vitrebond™,
the lateral walls and enamel were conditioned with acidic agent. Finally, the bonding agent was
applied as recommended by the manufacturer and the composite resin used to fill the cavity

Self-­Cure) or a resin-modified GIC (Riva Light-Cure) to line very deep cavities

prepared in human teeth [56, 57]. Although both cements were considered biocom-
patible for such clinical application, Riva Light Cure was more toxic to pulp cells
than Riva Self-Cure. In all these studies performed in human teeth, no postoperative
tooth sensitivity was reported by the patients, which might mistakenly indicate that
all ionomeric cements do not cause any damage to pulp tissue. Actually, we have
recommended lining deep cavity floors with resin-modified GICs rather than
7 Pulp Response to Clinical Procedures and Dental Materials 91

different formulations of CHC. This is because resin-modified GICs have several

important properties such as fluoride release, adequate flexural and diametral tensile
strength, elastic coefficient of thermal expansion and modulus of elasticity similar
to dentin, as well as chemical adhesion to both enamel and dentin, which are not
presented by all CHC formulations. However, based on the reliable body of scien-
tific data established by a number of well-conducted laboratory and clinical/histo-
pathologic trials, the most appropriate resin-modified GIC must be carefully selected
to be used in specific clinical situation to preserve the dentin-pulp complex health.
When pulp exposures mechanically created in human teeth were directly capped
with a resin-modified glass-ionomer cement, a wide displacement of uncured resin
and globules of glass occurred [57]. In this condition, the elicited chronic inflamma-
tory response did not allow regeneration of the dentin-pulp complex even after
almost 1 year after performing the clinical procedure. In this way, rather than resin-­
based materials, biocompatible dental products capable of stimulating dentin-pulp
regeneration should be used as capping agent.
The calcium silicate cements—Mineral trioxide aggregate (MTA) and Biodentine,
as well as specific formulations of calcium hydroxide—have been recommended as
capping agents. MTA and Biodentine present similar mechanism of action, which is
based on the release of calcium hydroxide and hydrated calcium silicate, increasing
the pH at the pulp wound site. Concerning primary teeth, these biocompatible mate-
rials have been indicated for pulpotomy in specific clinical situations of extensive
caries and pulp exposures but with no evidence of radicular pathology. Although
formocresol still has been considered the gold standard material for pulpotomy treat-
ments in primary teeth, MTA and Biodentine have demonstrated excellent perfor-
mance and high clinical/radiographic success rates [58]. This is because they are able
to maintain teeth integrity and preserve pulp vitality, allowing phonation, esthetics,
and masticatory function until exfoliation time [59, 60]. Despite the most of investi-
gations performed in human teeth using MTA or Biodentine as capping agents evalu-
ates the clinical and radiographic success rates, only a few of them has carried out
microscopic analysis of the dentin-pulp complex response against these calcium sili-
cate cements. Many years ago, researchers applied MTA directly on pulp exposure
performed in premolars of young patients, and the teeth were extracted for micro-
scopic analysis of the dentin–pulp complex [61, 62]. At short-time evaluation, the
authors demonstrated that components released from MTA displaced into the coro-
nal pulp. With time, these MTA components were observed in endothelial cells and
inside pulp blood vessels. These data should be carefully interpretated since dental
materials components inside blood vessels may result in embolism, which seems to
be a risk for patients’ health. Considering the fact that there is not a sufficient scien-
tific evidence to certify the safety of clinical application of Biodentine and new for-
mulations of MTA on pulp exposures, the use of such calcium silicate cements as
capping agent must be discussed at this time. New biological approaches based on
the application of tissue engineering knowledge associating scaffolds, bioactive mol-
ecules and stem cells for regeneration of the dentin-pulp complex have been assessed
in the last decades [63–65]. In this way, researchers have worked hard to develop and
improve innovative pulp-capping biomaterials capable of driving the regeneration of
92 J. Hebling et al.

the dentin-pulp complex mediated by resident stem cells. In a current study, chitosan
scaffolds capable of releasing bioactive concentrations of simvastatin was prepared
and assessed with the objective of developing a cell-free tissue engineering system to
be employed for pulp-dentin regeneration [63, 64]. Instead of causing an immediate
superficial necrosis to pulp cells, as observed when materials with high pH, such as
calcium hydroxide and calcium silicate cements, are used as capping agents, the new
simvastatin-­loaded scaffold increased the chemotaxis and regenerative potential of
pulp cells. When small concentrations of calcium were added to simvastatin-loaded
scaffold, the experimental biomaterial created a microenvironment capable of attract-
ing pulp cells to its surface and inducing the overexpression of odontoblastic markers
in a cell-homing strategy [64, 65]. Overall, rather than using synthetic dental materi-
als on pulp exposures that may have some adverse effects to resident stem cells, more
biological approaches have driven and improved the contemporary regenerative
dentistry.

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SDF as an Adjunct Approach
for the Management of Caries 8
Yasmi O. Crystal and Sasan Rabieh

Contents
8.1 Introduction 97
8.2 SDF’S Use for Caries Arrest 98
8.3 Appearance and Clinical Application 99
8.4 SDF’S Mechanism of Action in Enamel and Dentin 101
8.5 SDF on the Pulp Complex 103
8.6 SDF as an Indirect Pulp Therapy Agent 105
8.7 The Role of SDF in Caries Management 107
8.8 Conclusions 107
References 108

8.1 Introduction

Silver was known to have antibacterial properties since antiquity and has been used
for over a century in medicine as an antibacterial agent and to treat wounds and
burns [1].
In dentistry, silver has been used since the early 1900s for the management of
dental caries in different compounds, mainly as silver nitrate and Howe’s potion
(ammoniacal silver nitrate). The use of such compounds was advocated for the

Y. O. Crystal (*)
Department of Pediatric Dentistry, New York University, College of Dentistry,
New York, NY, USA
Comprehensive Pediatric Dentistry, Bound Brook, NJ, USA
e-mail: [email protected]
S. Rabieh
Department of Molecular Pathobiology, Division of Biomaterials, New York University,
College of Dentistry, New York, NY, USA
e-mail: [email protected]

© The Author(s), under exclusive license to Springer Nature Switzerland AG 2023 97

A. B. Fuks et al. (eds.), Contemporary Endodontics for Children and
Adolescents, https://doi.org/10.1007/978-3-031-23980-9_8
98 Y. O. Crystal and S. Rabieh

sterilization of infected dentin in deep caries lesions rather than mechanical removal
by bur or spoon with possible exposure and injury to the pulp [2].
More recently, silver has regained interest to treat dental caries in a minimally
invasive or nonsurgical manner. This has been popularized since the advent of silver
fluoride and silver diamine fluoride in different concentrations and preparations that
have been designed for different specific purposes: from disinfection of a lesion
prior to restoration, with the aim of dentin desensitization to caries arrest with and
without removal of carious tissues.
Silver diamine fluoride (SDF) was developed in Japan in 1969 as an agent for
caries arrest [3], and it was prepared as a clear liquid containing high concentrations
of silver as an antibacterial agent and fluoride as a remineralizing agent, stabilized
in an ammonia solution. Since then, many products with different concentrations
and indications have been introduced to the market in many countries, and their use
has been growing as an addition or an alternative to traditional restorative treatment.
In the United States, SDF at a 38% concentration was approved by the Food and
Drug Administration (FDA) in 2014 as a dentin desensitizing agent for patients over
21 years of age. Many clinical trials all over the globe have reported the success of
different concentrations used for caries arrest [4], and the American Academy of
Pediatric Dentistry (AAPD) issued a guideline in 2017 supporting its off-label use
for caries arrest in primary teeth as part of a comprehensive caries management
program [5]. The American Dental Association (ADA) followed in 2018, support-
ing the use of SDF over fluoride varnish for the arrest of cavitated coronal lesions [6].

8.2 SDF’S Use for Caries Arrest

SDF has gained popularity as an alternative to traditional restorative treatment

because it is relatively easy to apply. It does not require removal of carious tissue to
achieve caries arrest [7]; therefore, it doesn’t require the use of local anesthesia or
rotary instruments. It is relatively inexpensive and can be applied in many settings
because it does not require complex instruments or tools. It also poses minimal
risks, which has been confirmed in numerous clinical trials in preschool children
conducted all over the world, which have not reported any major or significant com-
plications from its use [4].
Clinical trials report arrest rates with SDF that range from 40% to 95% [8, 9].
Caries arrest is typically diagnosed when black staining and hardness of the surface
of the lesion are achieved, and the extent of the lesion stops its progression. Time to
arrest the lesion and sustained arrest depend on the concentration of the product
(12%, 30%, or 38%), frequency of application (once vs. twice a year), location of
the caries lesion in the mouth (anterior vs. posterior teeth), the location of the caries
lesion on the tooth (buccal, lingual, proximal, or occlusal), the effectiveness of
plaque removal after application, and the challenge of the dietary patterns of the
individual (frequency of exposure to cariogenic foods and beverages) [10, 11]. To
achieve caries arrest in cavitated dentin lesions, 38% SDF concentration is more
effective than lower concentrations, and application twice a year is more effective
8 SDF as an Adjunct Approach for the Management of Caries 99

than once a year [10]. A study that reported the arrest rates by area of dentition using
38% SDF twice a year stated that lower anterior teeth had 92% arrested lesions,
maxillary anterior teeth 86%, lower posterior teeth 62%, and maxillary posterior
teeth only 57% [11]. Occlusal surfaces required a longer time than buccal or lingual
surfaces to achieve caries arrest [10, 11]. Children that had a higher visible plaque
index score had a lower chance to have their caries arrested, [11] and children who
had more than three snacks or three times milk per day presented lower rates of
arrest [9]. For all these reasons, it is obvious that SDF does not work optimally as
an isolated therapy, but it yields best results when used in conjunction with a com-
prehensive plan for caries management that includes methods to reduce the cario-
genic challenge through plaque control and diet education. This is also very
important because SDF is contraindicated in teeth that are pulpally involved.
Therefore, in a comprehensive treatment plan for a child that may have pulpally
involved teeth, the appropriate pulp treatment and subsequent restoration or surgical
removal must be considered and planned according to the child’s expected coopera-
tion for treatment.
In addition to the characteristic black staining of treated lesions, SDF’s side
effects include a metallic taste immediately after application and gingival irritation
in some cases, especially when using products with higher pH. For this reason,
SDF’s use is contraindicated in patients who have silver allergies or who may have
stomatitis or ulcerative gingival lesions.
Although caries arrest with SDF is very effective for cavitated dentinal lesions,
several studies have shown that for the arrest of enamel lesions only, 5% sodium
fluoride varnish has similar effectiveness 10, [12]. One of the beneficial effects of
SDF is the immediate desensitization of dentinal tissues where it is applied. This
can be very helpful in the clinical management of caries especially with patients
who present with sensitive areas that prevent them from establishing an effective
oral hygiene routine.

8.3 Appearance and Clinical Application

SDF 38% as marketed in the USA, is a clear/blue liquid with metallic taste that
comes in a dropper bottle or in unit-dose ampules. One drop typically treats 4–6
lesions (depending on the size), and although the cost per lesion varies with the
individual product, the approximate cost per drop is US $1.
A sign of caries arrest is the dark staining of the decayed enamel and dentin.
Although sound enamel does not discolor, any areas of demineralized enamel
treated will also look black after SDF application (see Fig. 8.1a, b). Staining can be
more or less noticeable depending on the location of the cavities and the demineral-
ized areas that can come in contact with SDF during application. This characteristic
staining may pose esthetic concerns and can be a deterrent for its use.
A study that evaluated parental perception and acceptance of SDF’s staining
effects of parents from diverse backgrounds in New York City’s metropolitan area
found that parents found the use of SDF to be more acceptable on posterior regions
100 Y. O. Crystal and S. Rabieh

Fig. 8.1 (a) Cavitated and

non-cavitated lesions a
before SDF treatment; (b)
caries lesions in enamel
and dentin (cavitated and
non-cavitated) with typical
SDF staining

than on anterior regions where the black staining is visible. However, many parents
would allow for its use if it deferred or avoided more advanced forms of behavior
management to deliver treatment (like sedation or general anesthesia), which sug-
gests that many parents are open to compromising esthetics in favor of using a less
invasive approach for caries management. Even then, 40% of parents found the
treatment unacceptable under any circumstance on anterior teeth and 30% on poste-
rior teeth. Acceptability for treatment varied according to the parent’s educational
and economic status. For these reasons, the study recommends that to identify par-
ents who would be dissatisfied with the esthetic results, a thorough informed con-
sent with realistic photographs of treated teeth should be presented and discussed
[13, 14].
The use of potassium iodide (KI) after SDF or silver fluoride application was
introduced to remove excess ionized silver and eliminate or reduce the severity of
the staining [15]. Riva Star (SDI Limited. Victoria, Australia) developed a product
primarily marketed for dentin desensitization with KI to follow the SDF, or silver
fluoride application. The effectiveness of SDF for caries arrest when used together
with staining reduction by KI is limited. Results from a clinical trial using this tech-
nique to reduce the staining after SDF or silver fluoride application for caries arrest
8 SDF as an Adjunct Approach for the Management of Caries 101

Fig. 8.2 SDF application

in children report that lesions treated with KI after SDF or silver fluoride were less
likely to remain arrested [16].
SDF will also stain skin (temporarily) and other surfaces it comes in touch with,
so it must be handled with care. For its application, one should use the following
steps [17]:

• Dispense 1 drop for 4–6 teeth on a glass dappen dish.

• Clean the caries lesions thoroughly with a toothbrush.
• Place Vaseline on lips.
• Isolate with cotton rolls.
• Apply SDF with microbrush to caries lesion, and rub gently for 1 min (Fig. 8.2).
• Allow to air-dry.

Because the caries arrest varies depending on the size and location of the cavity,
it is recommended to bring back the patient 1–2 weeks later to confirm total arrest
and re-apply SDF if necessary. This is especially important when treating lesions in
posterior teeth, where the rates of arrest are lower with a single application [5].

8.4 SDF’S Mechanism of Action in Enamel and Dentin

The chemical formula for the SDF solution is [Ag(NH3)2]F, which consists of silver
diamine complex and fluoride ions [18], which are stabilized in an alkaline solution.
There are at least eight commercially available 38% SDF solutions across the world
[19], and the reported concentrations of silver are in the range of 248,000 to
287,000 ppm and 44,333 to 60,022 ppm for fluoride [18–21]. The pH of 38% SDF
solution is in the range of 9.1 to 10.0 in most commercial preparations. Products
with a higher pH would produce more gingival irritation when applied without a
rubber dam. The short-term stability of silver and fluoride ion concentrations seems
to be stable over 28 days [18, 22] for most products, but some seem to be out of the
range [19, 20]. Patel et al. reported that some products had much higher measured
102 Y. O. Crystal and S. Rabieh

concentrations for silver and fluoride that were at least 25% higher than the expected
concentration. So, it is recommended that clinicians use products that have been
tested by independent laboratories.
Silver in SDF has antibacterial effects [23]. In vitro studies report that the anti-
bacterial effects of silver ions on cariogenic bacteria like Streptococcus mutans
could be a result of the following three activities:

1. The ability to disrupt the bacterial cell wall structure through binding with disul-
fide anions in the protein membrane, which allows easy penetration through this
membrane.
2. Inhibition of DNA replication of bacteria through attaching to DNA’s guanine
component.
3. Cytoplasmic enzyme denaturation by binding to sulfhydryl (thiol) groups of cys-
teine, which interferes with the activity of essential enzymes [24] and bacterial
metabolism, inhibiting bacterial growth.

Silver also seems to inhibit collagen degradation by inhibiting cathepsins, and

the by-products of its precipitation may contribute to the rehardening of dentin [25].
However, many of the statements on SDF’s actions on bacterial communities have
been reached by studies conducted using in vitro biofilm models with single or
selected species combinations, when the oral microbiome involves at least 600 spe-
cies with complex interactions among them. Few studies have been conducted to be
able to elucidate the real action of SDF on bacterial communities within the dentin
where it is applied, in adjacent surfaces of the tooth, and its action on the whole oral
microbiome. Current studies have not been able to find significant microbial changes
in children with active caries following SDF applications and those with caries
arrested by SDF when testing plaque samples [26, 27]. Another recent study
reported that although they did not detect any changes in the microbial distribution
in the surface biofilm of SDF treated lesions, they found significant changes in the
microbiota of excavated subsurface dentin of SDF treated lesions, observing a
healthier community composition in the SDF treated dentin. Based on their find-
ings, they suggest that SDF’s antibacterial actions happen in the deeper region of the
lesion, ultimately arresting caries progression [28].
The high concentration of fluoride in SDF acts as a remineralizing agent,
strengthening enamel and dentin by forming fluorohydroxyapatite crystals.
Remineralized enamel and dentine crystals are less soluble to further acid attack,
which is also manifested in increased hardness of the tissue. The increase in levels
of calcium and phosphate in the surface layer of the arrested dentin caries lesion
after SDF treatment also results in increased microhardness [28]. Fluoride also
inhibits collagen degradation in dentin by inhibiting matrix metalloproteinases
activity. It is also proposed that silver and fluoride in alkaline solution have a syner-
gistic effect that seems to create an unfavorable environment for collagen enzyme
activation, therefore reducing dentin degradation [23, 25].
8 SDF as an Adjunct Approach for the Management of Caries 103

In terms of SDF penetration into the dental tissues, Li et al. in 2019 [29] used
scanning electron microscopy energy-dispersive X-ray spectroscopy (SEM-EDS) to
study silver penetration and precipitation in enamel and dentin. Their results show
that silver penetrates into both demineralized enamel rods (even without cavitation)
and dentinal tubules, and the degree of silver penetration was positively related to
the degree of enamel and dentin demineralization. They suggested that silver oxide,
silver sulfide, and/ or silver phosphate could be the main culprits of the black stain
on the surface of treated carious lesions and that penetration and precipitation of
silver in treated carious lesion can reach depths of approximately 2500 μm, which
can reach the dental pulp tissue [29]. Using similar methodology, Sulyanto et al. in
2021 observed that after SDF application, multiple dentinal tubules were occluded
by silver, while some others were occluded by calcium phosphate [30].

8.5 SDF on the Pulp Complex

Other chapters have described the changes that occur in pulpal tissues since the very
early stages of bacterial invasion of the dentin and the changes that are elicited in the
pulp when different materials are applied to open dentinal tubules. Therefore, it is
expected that regardless of the aim for which SDF is used (desensitization or caries
arrest), it is going to have very specific responses from the pulpal tissue, perhaps
depending on the depth of the lesion to which it is applied, its mineral loss, and the
proximity to pulp cells.
It has been reported since early studies that direct application of silver com-
pounds directly on the pulp causes pulp necrosis [2, 31], but few recent studies
report the effects of SDF on the pulp when it is applied on dentin. One study applied
SDF to cavities prepared on virgin premolars scheduled for orthodontic extractions
and compared the pulpal effect to glass ionomer cement (GIC), calcium hydroxide,
and no treatment control [32]. Premolars were extracted 6 weeks later, and histo-
logical examination was done. No inflammatory changes were observed in any of
the groups, and significantly more specimens in the SDF and GIC groups showed
tertiary dentin deposition (TDD) when compared to the control group. The study
demonstrated the TDD-inducing ability of SDF and Type VII GIC and also estab-
lished their biocompatibility when used as IPT materials [32]. But this study was
done on sound teeth (with no previous pulpal reaction to the carious process), and
changes were only assessed at 6 weeks.
Another case report describes the histological characteristics of a primary tooth
with deep caries in proximity to the pulp after 6 months treatment with SDF, which
was extracted when it was deemed to be non-restorable [33]. Their light microscopy
observations revealed no carious pulp exposure, evidence of tertiary dentin forma-
tion, and minimal pulp inflammation. An intact but flattened odontoblastic layer
was found adjacent to the irregular tertiary dentin, dentinal tubules with silver
deposits to a depth of 1 mm, and no visible bacteria. They conclude that SDF leads
104 Y. O. Crystal and S. Rabieh

to histologic changes that prevent pain and pulp deterioration and most likely facili-
tate pulp healing [33]. It is important to stress that this is a report from a single
specimen, and the observations with light microscopy are limited in terms of iden-
tification of silver deposition in pulp tissues with no possible visible staining.
Additionally, identification of bacteria at 20× magnification with hematoxylin and
eosin stain would be very limited.
Another ex vivo study reported the findings on the pulp complex of eight pri-
mary teeth with dentin-enamel caries. The teeth were extracted after 1 year of
SDF application [34]. Scanning electron microscopy (SEM) showed areas of
hypermineralization in the intertubular dentin and few blocked tubules, while
energy-dispersive X-ray detector (EDS) done on only one sample detected the
presence of silver in the center of the lesion, and its concentration declining at the
edges, with no silver observable in the areas farthest from the lesion. Bright-field
optical microscopy (OM) showed SDF sealing the tubules only in the surfaces
where it was applied, with limited penetration beneath. The tubules appeared nor-
mal, and the pulp tissue under treated areas showed chronic inflammatory infil-
trate and formation of tertiary dentin, with no silver precipitation. From their
observations using the different techniques, they concluded that SDF causes mini-
mal adverse effects on pulpal tissues.
Another ex vivo study done by Sulyanto et al. in 2021 confirms the formation of
tertiary dentin regions located around and inside the pulp chamber, with thicker
tertiary dentin in teeth treated with SDF over longer periods of time [30].
A recent systematic review was performed specifically to collect all published
data on the pulp response to SDF up to 2021 [35] and found only five publications
that dealt specifically with this theme (including the first three described above).
Grouping the results of these three studies with additional animal studies, they com-
prised data from a total of 30 teeth and reported that indirect SDF application caused
none or only mild inflammatory response of dental pulp, with odontoblasts showing
increased cellular activity. Tertiary dentin was formed in the pulpal side of the cav-
ity with indirect SDF application, with accentuated incremental lines of tertiary
dentin reflecting disturbances in mineralization. Silver ions were found to penetrate
along the dentinal tubules but were not detected inside the pulp in most studies.
They concluded that SDF application directly onto pulp tissue causes pulp necrosis
but that indirect SDF application (to carious dentin) is generally biocompatible,
causing only a mild inflammatory response, increased odontoblastic activity, and
increased tertiary dentin formation.
The results of all of these studies indicate that as long as the pulp tissue is still
vital, when SDF is placed on dentin, even without caries removal, its remineral-
izing actions harden the dentin and block dentinal tubules, and the antibacterial
effects reduce or eliminate bacteria in the remaining dentin, allowing the pulp to
heal and produce tertiary dentin to further seal against the bacterial invasion
(Fig. 8.3).
8 SDF as an Adjunct Approach for the Management of Caries 105

a b

Fig. 8.3 (a) SEM image of a carious lesion in human tooth treated with SDF: EDS analyses con-
firms the silver penetration and deposition in dentin and dentinal tubules (white spots); (b) tertiary
dentin formed after SDF treatment (EN Enamel; DN dentin; TD tertiary dentin). (Image copy-
righted by Drs. Crystal and Rabieh, who thank Bin Hu’s assistance for SEM-EDS imaging and
analysis. The Zeiss Gemini 300 FE-SEM was provided courtesy of the National Institutes of
Health S 10 Shared Instrumentation Program, grant number 1S10OD026989-01)

8.6 SDF as an Indirect Pulp Therapy Agent

There are only a few clinical studies done that have evaluated the clinical response
of the pulp to SDF when used for indirect pulp therapy. Divyashree et al. in 2021
[36] evaluated the clinical and radiographical success of SDF 38% applied for 15 s
vs. Dycal and MTA, including 25 primary molars on children aged 5–9 years in
each group. The molars included in the study had caries lesions extending into 2/3
of the dentin with no spontaneous pain, and all teeth had selective caries removal
and were restored with resin-modified glass ionomer cement (RMGIC). Any
observed reparative dentin layer was measured radiographically and compared
between groups. After 6 months, teeth treated with SDF had formed a good biologi-
cal seal, further caries progression was arrested, and the SDF did not cause any
adverse pulpal reaction. However, the amount of reparative dentin formed was high-
est in the Dycal group, followed by the MTA group with the lowest in the SDF
group. Although there was no mention of clinical success and the study only fol-
lowed cases for 6 months, they concluded that SDF seems to be a good IPT material
as it presents with good biological seal and maintenance of pulp vitality.
In another clinical study, Patil et al. in 2021 [37] did an evaluation of 38% SDF
applied for 2 min onto excavated dentin and compared it to a 1.5 mm. layer of cal-
cium hydroxide as IPT on primary teeth on children aged 4–7 years that were fol-
lowed for 6 months with 25 teeth in each group. Both groups had selective caries
removal and were restored with RMGIC restorations. SDF showed 96% success
rate at 6 months follow-up, whereas calcium hydroxide showed 88% success. They
reported no statistically significant difference between the groups, so they conclude
that SDF can be used as an effective alternative for IPT in primary molars.
106 Y. O. Crystal and S. Rabieh

In a more recent clinical trial, Shafi et al. in 2022 [38] studied the effects of
diluted SDF (1:10) applied for 2 min onto excavated dentin and compared it to light-­
cured calcium hydroxide as IPT in 56 primary molars (28 in each group) with no
signs of spontaneous pain [38]. All teeth had selective caries removal, glass ionomer
cement was placed after the indirect pulp therapy agent, and they all were restored
with preformed metal crowns (SSCs). They report no radiographic failures at
12 months but one clinical failure in the SDF group and two in the calcium hydrox-
ide group, resulting in 96% success for SDF and 92.7% for calcium hydroxide with
no statistical significance between the groups. Tertiary dentin deposition and discol-
oration of the tooth could not be evaluated as the teeth were restored with SSCs, but
they conclude that 1:10 SDF diluted solution could be an alternative to calcium
hydroxide for IPT in primary teeth [38].
Another recent RCT studied the clinical and radiographic effectiveness of SDF
38% with and without potassium iodide (KI) when used as indirect pulp therapy on
deep carious lesions in young permanent molars restored with RMGIC (36 molars
in each group) and compared it to RMGIC used as an IPT agent, followed by a
resin-based composite restoration [39]. All molars had selective caries removal
before the application of the pulp therapy agent. After 12 months, one failure was
reported in each of the SDF and SDF + KI groups, but this showed no statistical
significance in overall success between the three groups. Secondary caries was
noted in only two teeth in the SDF + KI groups, but this resulted in no statistical
significance between the three groups. However, they found a significant difference
in the restoration color, marginal staining, and luster of the restoration, with the
RMGIC group having better results than both SDF groups. They conclude that
although all materials were successful at preserving pulp vitality and preventing
pain, the RMGIC group showed better esthetic restorative results than the SDF
groups [39].
In the USA, the original labeling of SDF and silver fluoride products was and
still is as a desensitizer. Products like Riva Star (SDI Limited, Victoria, Australia)
were originally marketed to reduce or eliminate dentin sensitivity on deep caries
lesions. A promotional video shows it as part of the restorative treatment using a
“sandwich technique” where the silver fluoride product would be applied after
selective caries removal and acid etching followed by KI to reduce the staining.
After rinsing thoroughly, a RMGIC was placed up to the dentin-enamel junction,
covered with bonding agent, and a composite resin was placed in the surface. Since
the product had a pH of 13, it was recommended to use rubber dam isolation [40].
In this technique, the first product to be placed in contact with the recently exca-
vated dentin was silver fluoride, so in fact it would act as IPT, which would result in
dentin desensitization.
8 SDF as an Adjunct Approach for the Management of Caries 107

8.7 The Role of SDF in Caries Management

All of the laboratory and clinical evidence to date indicate that the effect of SDF
spans throughout the surface and body of the carious lesion and into the pulp cham-
ber. Whether it is used as a desensitizer agent in IPT as part of a restorative tech-
nique with selective caries removal or by itself as a caries arrest medicament with
no caries removal, it seems that the immediate formation of a hard barrier that may
impede the progression of cariogenic microbes or their metabolites into dentin gives
the pulp tissue time for healing, allowing formation of tertiary dentin and resulting
in desensitization. All of these actions make SDF an invaluable tool for caries man-
agement. Although the staining it produces may limit its use as IPT on patients who
prefer esthetic restorative treatment, its use as a caries arrest agent on patients who
can’t receive traditional restorative treatment is invaluable. Patients who are very
young, the elderly, patients with special healthcare needs, those whose treatment
has to be delayed for health or other reasons, individuals that encounter barriers for
the provision of care, or those who prefer a minimally invasive approach for their
dental treatment can now have the alternative of choosing a therapy that can delay
or defer more complicated and expensive options. Hard-to-clean lesions with per-
sistent plaque deposits can be selectively restored with RMGIC, and dark arrested
lesions can be covered with esthetic restorative options at a later date according to
the patient’s situation and preferences.
Eliminating sensitivity of exposed lesions can allow for implementation of
improved home care routines that in turn will help sustain the arrest of the lesions
and lead to improved oral health. The evidence we have included in this chapter
indicates that in order to achieve this, a reduction of the frequency of ingestion of
cariogenic snacks and beverages through dietary counseling is also required. In
order to evaluate and reinforce the lifestyle habits that affect the success of SDF, as
well as to monitor lesions and re-apply SDF therapy as indicated, frequent re-care
on these high caries-risk patients is imperative [41].
For all these reasons, we stress that the use of SDF should be part of a compre-
hensive caries management plan with the aim of leading the patient to sustained
oral health.

8.8 Conclusions

SDF’s antibacterial and remineralizing effects on treated dentin, which result in

reduced bacterial load, reduced dentinal degradation, and dentinal tubules blockage,
seem to allow the pulp to recover from the bacterial attack, inducing desensitization
and formation of tertiary dentin. Its use as a single agent, or followed by a restora-
tion that will further seal the dentinal tubules and protect the pulp complex, is an
invaluable tool in the management of dental caries, especially when other means for
treatment are not available.
108 Y. O. Crystal and S. Rabieh

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Guidance to Achieve Clinical Pulpal
Diagnosis and Operative Decisions 9
Marcio Guelmann and Roberta Pileggi

Contents
9.1 Introduction 112
9.2 Clinical Examination 114
9.3 Diagnostic Tests 115
9.3.1 Electrical Pulp Test (EPT) 115
9.3.2 Cold Test 116
9.3.3 Heat Test 116
9.3.4 Laser Doppler Flowmetry (LDF) 117
9.3.5 Pulse Oximetry 117
9.3.6 Periapical Tests (Percussion) 117
9.3.7 Probing 117
9.3.8 Periapical Image 117
9.4 Depth of Caries and Presence of Symptoms 119
9.5 Bleeding and Pulpal Status 120
9.6 Pulpal Diagnosis Terminology 121
9.7 Conclusion 122
References 124

M. Guelmann (*)
Department of Pediatric Dentistry, University of Florida College of Dentistry,
Gainesville, FL, USA
e-mail: [email protected]
R. Pileggi
Department of Endodontics, University of Florida College of Dentistry, Gainesville, FL, USA
e-mail: [email protected]

© The Author(s), under exclusive license to Springer Nature Switzerland AG 2023 111
A. B. Fuks et al. (eds.), Contemporary Endodontics for Children and
Adolescents, https://doi.org/10.1007/978-3-031-23980-9_9
112 M. Guelmann and R. Pileggi

9.1 Introduction

The etiology for pulpal and periapical diseases is mainly related to caries and/or
traumatic injuries. It is well established in the literature that improper diagnosis and
preventive treatment can result in patients’ visits to the emergency room that other-
wise could be avoided [1, 2]. Reaching an accurate diagnosis is the goal of every
practitioner treating any condition. The road to achieve this goal is not always
straightforward. It consists of collection, assessment, and interpretation of relevant
information such as (a) medical, dental, and social histories; (b) chief complaint and
presence of signs and symptoms; (3) objective clinical tests in combination with
clinical and radiographic examinations; (4) establishment of a tentative diagnosis by
comparing clinical and subjective findings; and (5) final diagnosis when the opera-
tive approach is executed [3].
When treating children, some of the information compiled may be subjective in
nature and not always directly obtained from the child but from the parent or care-
giver. Some sensibility tests such as thermal and electric are of limited use in pre-
school children, not because of questionable accuracy but mainly due to anxiety and
the potential of promoting disruptive behavior and the reliability and reproducibility
of the responses obtained [4]. However, the experienced and talented clinician
together with his/hers must-needed bond with the patient and the use of efficient
behavior guidance techniques may allow some of these tests to be performed at an
early age. A decision tree or flowchart for guidance on how to achieve treatment
decisions is a desirable tool to have. Exceptions to these guidelines may include, but
not limited to, patients with complex medical histories, the child’s ability to cooper-
ate, restorability of the tooth, financial considerations, and parental preferences [5].
One can only diagnose pathology when healthy and normal structures are known
and familiarized by the clinician. Facial swelling and the presence of lymphade-
nopathy in submandibular and cervical areas are abnormal extraoral features
(Fig. 9.1). Intraoral swelling, sinus tract and fistula adjacent to a tooth or teeth with
history of trauma, deep carious lesion or previous existing restoration, abnormal
mobility, and sensitivity to percussion when a tooth is not close to its natural exfo-
liation time are signs of concern (Fig. 9.2a, b) [6].
Radiographically, in primary molars, lack of lamina dura and furcation radiolu-
cency and presence of internal and/or external resorption indicate advanced pulpal
degeneration (Figs. 9.3 and 9.4). In primary canines and incisors with deep caries
lesions of after traumatic injuries, widening of the periodontal ligament around the
root surface and/or periapical area may indicate pathology or infection. In those
situations, conservative treatment is no longer possible.
9 Guidance to Achieve Clinical Pulpal Diagnosis and Operative Decisions 113

Fig. 9.1 Facial swelling

as result of an odontogenic
infection involving a
mandibular left second
primary molar. Fever and
restricted mouth opening
required hospital
admission for IV
antibiotics

a b

Fig. 9.2 (a) Apical fistula as result of incisal caries on maxillary primary canine on a 3-year-old
child. (b) Periapical radiograph of the same tooth, showing interruption of continuation of root
development as result of pulp necrosis

Fig. 9.3 Internal root

resorption on tooth #K (75)
as result of deep caries and
chronic inflammation
114 M. Guelmann and R. Pileggi

Fig. 9.4 Deep carious

lesion with furcation,
widening of the
periodontal ligament, and
periapical involvement on
tooth #T (85)

9.2 Clinical Examination

During clinical examination, it is important to ask questions related to the location,

duration, intensity, initiator, and inhibitor of pain. Additionally, it is very helpful to
note the child’s behavior and possible clues about the pain such as the holding of a
specific area of the jaw and the history of provoked, nocturnal, or spontaneous pain.
In the presence of diffuse or localized swelling, the palpation test will determine the
extent and type of swelling (indurated or fluctuant), and body temperature is
recorded (Fig. 9.1). Lymph nodes of the neck also need to be palpated to determine
any possible systemic involvement. Some of the infections associated with posterior
teeth, especially mandibular and maxillary molars, can be extremely dangerous and
may require emergency treatment at the hospital since swelling may compromise
the airway. Areas of extensive decay, traumatic injuries, and defective restorations
also have to be examined.
The determination of the pulpal and periapical diagnosis is quite complex. The
pulpal tissue is a connective tissue composed of nociceptive fibers. The main fibers
are the myelinated A δ and unmyelinated C fibers. These nociceptive fibers play an
important role during the vitality test of the pulp when the tooth is either stimulated
by a thermal or an electrical current (EPT) [7, 8]. Cold and EPT do not assess pulpal
vitality but the response of the nociceptor fiber to a cold and electrical stimulus,
which indicates the inflammatory condition of the pulp when a chief complaint is
reproduced. The reliability of the vitality test is not 100%. Peterson et al. demon-
strated that 83% of the teeth with a necrotic pulp were identified as necrotic by the
cold test, while 93% of the teeth with vital pulp were identified as vital by the cold
test. When the electrical test was used, 72% of the teeth with necrotic pulp were
identified as necrotic, while 93% of the vital teeth were identified as vital [8]. The
lack of accuracy and the presence of false-positive and false-negative responses
increase the challenge of determining a proper pulpal diagnosis. The lack of correla-
tion of clinical and histological diagnosis of irreversible pulpitis could be as high as
84.4% [7, 8]. Multirooted teeth also can be partially necrotic, and due to remaining
vital tissue in one of the roots and the fact that nerve fibers are the last to die, a
9 Guidance to Achieve Clinical Pulpal Diagnosis and Operative Decisions 115

normal response will still be elicited when cold is applied, despite the necessity of
root canal treatment due to a diseased pulp [7–9]. When treating pediatric patients,
it is important to remember that due to the incomplete development of the plexus of
Raschkow, until the teeth are fully occluded, the electrical test becomes more unre-
liable [9]. Therefore, the necessity of a good clinical history, current clinical find-
ings, and a proper image of the tooth is of paramount importance. The lack of
correlation between clinical and histological findings is well established and
increases the clinician’s complexity for a proper diagnosis with the vitality tests we
routinely use [10, 11].
Sensibility is defined as the ability to respond to a stimulus [10–12], and hence
this is an accurate and appropriate term for the typical and common clinical pulp
tests such as thermal and electric tests given that they do not detect or measure blood
supply to the dental pulp. The most accurate way of diagnosing pulpal disease
would require histological evaluation, which is not feasible. Therefore, the clinician
must rely on the diagnostic tools presented in this chapter and on the importance of
reproducing the patient’s chief complaint. In young permanent teeth, sensibility
tests used for pulpal diagnosis are EPT, cold, and heat (when the chief complaint is
pain to heat).

9.3 Diagnostic Tests

9.3.1 Electrical Pulp Test (EPT)

It is important to note that the pulpal response to the electrical current is not an
indication of pulpal vitality or the health status of the pulp but the response of the
sensory fibers of the pulp to an electrical stimulus. This stimulus stimulates mainly
the myelinated Aδ fibers located at the odontoblastic layer of the pulp, since the
unmyelinated C fibers located at the pulp proper require a higher stimulation [12,
13]. When using the EPT, the clinician should focus on a response or non-response,
rather than the numerical value associated with the impulse sensation (Fig. 9.5).

Fig. 9.5 Electric pulp test

after trauma on a maxillary
permanent incisor
116 M. Guelmann and R. Pileggi

9.3.2 Cold Test

The thermal test is one of the most used sensibility tests to determine the vitality of
the pulp. In the past, different tests were used for cold, such as ice tubes, CO2 snow,
and a refrigerant spray (Endo-ice). Their mechanism of action occurs by initiating
fluid movement at the odontoblastic layer of the pulp, resulting in the generation of
action potentials in the nerve ending [14]. The temperature obtained with the CO2
snow is −78.1 °C; with a ball of cotton pellet sprayed with the refrigerant, it is
approximately −50.1 °C. When testing with cold or any thermal test, it is important
to test a similar tooth that is not the offended one and appears normal to obtain a
baseline test for comparisons. This will also decrease the child’s anxiety. With the
advances of new research, it is established that Endo-ice even in the presence of
crowns is a very viable test, since it causes a reaction to the stimuli quicker than the
one caused by CO2 snow despite the lower temperature. When the cold test is
applied on the tooth, a normal response is considered when the sensation is felt by
the thermal application but disappears after the removal of the stimuli without
inducing a painful or lingering response. An unusual response is obtained when the
application of the stimulus triggers moderate-to-severe pain due to an irreversible
degree of inflammation, or it does not elicit any sensation, which could indicate
necrosis or calcification of the pulp (Fig. 9.6a, b).
Cold and EPT can be successfully performed in children at the early mixed den-
tition stage and serve as an indicator of the status of the pulp. Clinicians need to take
into consideration the limitations of this type of tests, especially in pre-cooperative
or patients with special needs [15–17].

9.3.3 Heat Test

This test is only indicated when a patient’s chief complaint is pain on heat. One of
the best ways to test heat is by isolating the arch with a split dam isolation and test-
ing each tooth with a cotton ball of hot water. If the chief complaint is reproduced,
the clinician can then diagnose the offending tooth.

a b

Fig. 9.6 (a) The refrigerant spray (Endo-ice) placed on a ball of cotton pellet instead of a cotton
tip applicator for better transfer of cold; (b) the sprayed cotton pellet applied to the midfacial area
of the tooth or crown
9 Guidance to Achieve Clinical Pulpal Diagnosis and Operative Decisions 117

9.3.4 Laser Doppler Flowmetry (LDF)

Laser Doppler measures the blood flow by the dissemination of an infrared light
through the pulpal tissue and the difference in frequencies when contacting red
blood cells. This average frequency shift measures the velocity at which the red
blood cells are moving [18, 19]. Many studies have demonstrated the use of LDF for
pulpal vitality, especially following traumatic injuries. However, its use in clinical
settings is not completely established due to the high cost, differences on pulp
chambers due to calcifications, “noise” created by the backscattered light in contact
with tissue, and the inability to create a baseline to compare normal to diseased.

9.3.5 Pulse Oximetry

This test assesses vascular integrity by measuring the oxygenation of blood.

However, the validity of its use in clinical practice is still controversial [20, 21].

9.3.6 Periapical Tests (Percussion)

This test evaluates the status of the periodontium surrounding the tooth. It is best
performed by tapping the handle of the clinical mirror along the long access of the
tooth at the occlusal or incisal surface of the tooth and horizontally on a 90-degree
angle with the crown (Fig. 9.7a, b).
In young children, the use of the tip of the finger to test percussion sensitivity is
a well-accepted method. Clinicians must be aware of potential false-positive
response to percussion caused by food impaction when large proximal lesions are
present, which may result in inflammation of the papilla instead of pulpal in
nature [22].

9.3.7 Probing

Periodontal probing is important to assess any possible periodontal involvement and

potential vertical root fractures (Fig. 9.8).

9.3.8 Periapical Image

A proper periapical image is of paramount importance for the pulpal and periapical
diagnosis and overall treatment planning in endodontics. In addition to periapical
images, a limited focal view CBCT has been instrumental for earlier detection of
resorption in traumatized teeth (Fig. 9.9a, b). Additionally, when taking periapical
images, according to a classical study from Brynolf, an accurate diagnosis was
118 M. Guelmann and R. Pileggi

a b

Fig. 9.7 (a) Percussion test on incisal edge and (b) percussion test on the facial surface of the tooth

Fig. 9.8 Periodontal

probing

a b

Fig. 9.9 (a) Periapical image of teeth #s 8 and 9. CC: tooth hurts after I hit my mouth on the
basketball arch. (b) Early signs of inflammatory root resorption detected by the limited view
CBCT. Vitality test was giving a normal response to Endo-ice and EPT. RCT was initiated, and
symptoms went away
9 Guidance to Achieve Clinical Pulpal Diagnosis and Operative Decisions 119

Fig. 9.10 The importance of angled radiographs for better diagnosis. The horizontal root fracture
would not be detected if only one angle radiograph was taken

obtained with 90% accuracy when three radiographs were taken in different angles
as compared to 74% of accuracy when one straight angle is obtained (Fig. 9.10) [23].

9.3.8.1 Focal View CBCT

The American Association of Endodontists and the American Academy of Oral and
Maxillofacial Radiology in 2015 published a revised joint position statement on the
use of CBCT in endodontics [24]. Among several indications for its use, both asso-
ciations advocate the use of CBCT in traumatic injuries and as a tool to assist on
complex cases of diagnosis (Fig. 9.9b).

9.4 Depth of Caries and Presence of Symptoms

It is important to remember that when caries is the main etiology, the clinician needs
to thoughtfully diagnose the pulpal and periapical tissues to determine the treatment
that can provide the best long-term outcome to the patient. If the carious tissue is not
properly removed and restoration not properly sealed, especially in patients with
high caries risk, bacterial by-products will continue to move through the dentinal
tubules inducing more inflammation and further pulpal necrosis [7, 25, 26]. To fur-
ther decrease the chance of a good outcome, the pulp has a restricted healing poten-
tial. This is caused by the lack of collateral supply, microcirculation, and the rigid
structure, by which the pulp is surrounded by.
Since the histopathologic status of the pulp is currently impossible to be obtained,
determination of pulp vitality in primary teeth with deep carious lesions or after
trauma is more of an art than science. Coll et al., for example, suggested interim
therapeutic restorations for deep carious lesions as a practical tool for determination
if a conservative pulp therapy approach is possible [27]. Kassa et al. [28]
120 M. Guelmann and R. Pileggi

demonstrated that in occlusal and proximal lesions less than 50% deep into dentin,
pulp inflammation should be minimal to none. However, when positive history of
pain exists and the depth of caries is more than 2/3 into dentin and remaining dentin
thickness equal to or less than 1.0 mm, presence of inflammation was a common
histological finding on both coronal and radicular portions of the pulp in affected
second primary molars [29]. Selection of a conservative approach, such as selective
caries removal, may be contraindicated in these situations.

9.5 Bleeding and Pulpal Status

According to Aminabadi et al., accidental pulp exposures in primary molars resulted

in much lighter bleeding color than when caries exposure occurred and pulpotomy
was performed [30]. Darker bleeding color in primary molars was considered an
indication for a more aggressive treatment approach such as pulpectomy in some
studies (Fig. 9.11) [30, 31].
The ability to obtain hemostasis at the canal orifices has been a clinical indica-
tion for a potential health status of the radicular pulp [3]. However, a recent study
demonstrated that the achievement of hemostasis did not provide accurate assess-
ment of the inflammatory status of the pulp at the canal orifices and should not be
used as criterion for pulpotomy [32].

Fig. 9.11 Dark bleeding

in a primary molar with a
history of nocturnal and
spontaneous pain.
Pulpectomy or extraction
may be indicated
9 Guidance to Achieve Clinical Pulpal Diagnosis and Operative Decisions 121

9.6 Pulpal Diagnosis Terminology

The pulpal diagnosis can be normal, reversible, symptomatic irreversible pulpitis,

necrotic, and previously treated. The tables below explain the clinical diagnostic
terminology (Table 9.1) and periapical diagnostic terminology (Table 9.2) of the
pulpal disease obtained from the American Association of Endodontics (AAE)
Consensus Conference Recommended Diagnostic Terminology [33].

Table 9.1 The clinical diagnostic terminology of pulpal disease obtained from the American
Association of Endodontics (AAE) Consensus Conference Recommended Diagnostic
Terminology (2009)
Normal The pulp is symptom-free and responds normally to pulp testing. No
history of pain or sensitivity
Reversible Patients usually complain about hypersensitivity to cold and/or sweets that
goes away when the stimulus is removed. The subjective and objective
findings demonstrate that the inflammation should subside and pulpal
tissue reverse to normal when the etiology is removed
Symptomatic Patient presents with pain or history of unprovoked pain. When the cold
irreversible stimulus is applied, the pain is severe or lingers. The main etiologies are
pulpitis deep caries, extensive restorations, or fractures exposing the pulpal tissues.
The pulp cannot heal, and the inflammation cannot be reversed to normal.
Root canal treatment is indicated
Asymptomatic Vital inflamed pulp is incapable of healing, and root canal treatment is
irreversible indicated. These cases have no clinical symptoms and usually respond
pulpitis normally to thermal testing but may have had trauma or deep caries that
would likely result in exposure following removal (Fig. 9.12)
Necrotic A clinical diagnosis indicating death of the pulp tissue. The pulp is usually
non-responsive to sensitivity testing
Previously treated Indicates the diagnosis of a tooth that had been endodontically treated and
the canals obturated

Table 9.2 The clinical diagnostic terminology of the pulpal and periapical disease obtained from
the American Association of Endodontics (AAE) Consensus Conference Recommended
Diagnostic Terminology (2009)
Normal The periapical tissue surrounding the root of the tooth appears normal.
The lamina dura is intact. The percussion and palpation tests are normal,
not eliciting any pain and or discomfort
Symptomatic apical The periapical tissue is inflamed. Pain to percussion and/or palpation. CC
periodontitis might be associated with pain from biting. Periapical radiolucency might
or might not be present
Asymptomatic Patient presents with no pain to percussion and/or palpation.
apical periodontitis Inflammatory reaction has caused the presence of a periapical
radiolucency
Chronic apical Characterized by an inflammatory reaction to pulpal infection and
abscess necrosis with little or no discomfort and the presence of a sinus tract
Acute apical A clinical diagnosis indicating death of the pulp tissue. The pulp is
abscess usually non-responsive to sensitivity testing. Characterized by rapid
onset, spontaneous pain, and pain to percussion and palpation. Presence
of swelling and pus
Condensing osteitis Characterized by diffuse radiopaque lesion representing a localized bone
reaction to a low-grade inflammatory stimulus, usually seen at the apex of
the tooth
122 M. Guelmann and R. Pileggi

9.7 Conclusion

As previously stated, one of the main challenges in dentistry is the ability to prop-
erly diagnose. Despite the advances in technology, at this point, we are still relying
on cold and an electrical current as the main tools for the diagnosis of the pulpal
tissue. The advances in biological markers and in image modality with artificial
intelligence will hopefully bring another tool for us practitioners. In the meantime,
we clinicians need to understand the subjectivity of the vitality tests and remember
that the bacterial by-products will cause an inflammatory and chronic infection that
could lead to pulpal necrosis, despite a normal response to vitality tests.
The case below illustrates a tooth that was diagnosed as normal pulp despite the
large amount of caries in proximity to the pulp chamber and the previous history of
pain (Fig. 9.12a–d).

Fig. 9.12 (a) 15-year-old male patient with large occlusal caries and high caries risk due to poor
hygiene and diet. Due to a normal response to the vitality test, the tooth was diagnosed as normal
pulp rather than asymptomatic irreversible pulpitis. An indirect pulp capping was performed. Four
weeks later, the patient had severe percussion pain and a dull pain on the lower arch. (b) Presence
of a periapical radiolucency, soft carious tissue encountered under the permanent filling near the
Dycal liner. Vitality tests were performed and tooth diagnosed as necrotic with symptomatic apical
periodontitis. (c) As noted, the tissue looked unhealthy, and the other two canals appeared necrotic.
(d) Root canal treatment was performed and symptoms subsided. Patient received a full-­
coverage crown
9 Guidance to Achieve Clinical Pulpal Diagnosis and Operative Decisions 123

d
124 M. Guelmann and R. Pileggi

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gency department visits with dental conditions among children in the United States: nation-
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4. Nagarathna C, Shakuntala BS, Jaiganesh I. Efficiency and reliability of thermal and electrical
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apy for primary and young permanent teeth. Switzerland: Springer International Publishing;
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clinical study. Eur Arch Paediatr Dent. 2021;22:693–7.
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of human teeth. Endod Dent Traumatol. 1994;10:185.
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Management of Deep Dentin Carious
Lesions: A Contemporary Approach 10
for Primary and Young Permanent Teeth

Marisa Maltz, Luana Severo Alves,

Fernando Borba de Araújo, and Anna B. Fuks

Contents
10.1 Introduction 128
10.2 Dental Caries Lesion Development and Pulp Reactions 128
10.3 D ifferent Stages of Dental Caries Lesions, Dental Tissue Bacterial Invasion,
and Lesion Control 129
10.4 Treatment Options for Deep Dentin Carious Lesions 131
10.5 Clinical Evidence for Primary Teeth 136
10.6 Clinical Evidence for Permanent Teeth 137
10.7 Pulp Response to SCR-SD 138
10.8 The Role of Cavity Liners After SCR-SD 139
10.9 Future Perspectives for the Management of Deep Carious Lesions 140
10.10 Concluding Remarks 142
References 142

M. Maltz (*)
Preventive and Social Dentistry, Faculty of Dentistry, Federal University of Rio Grande do
Sul, Porto Alegre, RS, Brazil
L. S. Alves
Department of Restorative Dentistry, School of Dentistry, Federal University of Santa Maria,
Santa Maria, RS, Brazil
F. B. de Araújo
Department of Oral Surgery and Orthopedics, Faculty of Dentistry, Federal University of Rio
Grande do Sul, Porto Alegre, RS, Brazil
e-mail: [email protected]
A. B. Fuks
Department of Pediatric Dentistry, Hadassah Medical Center, Faculty of Dental Medicine,
Hebrew University of Jerusalem, Jerusalem, Israel
e-mail: [email protected]

© The Author(s), under exclusive license to Springer Nature Switzerland AG 2023 127
A. B. Fuks et al. (eds.), Contemporary Endodontics for Children and
Adolescents, https://doi.org/10.1007/978-3-031-23980-9_10
128 M. Maltz et al.

10.1 Introduction

Caries prevalence is still high worldwide, with the disease burden affecting all age
groups [1]. When biofilm control and preventive measures fail, a carious lesion is
expected to develop. Following its natural developmental history, the lesion will
advance through the enamel and reach the dentin, leading to pulp infection and
necrosis.
If appropriate control measures are implemented, such as biofilm control, adop-
tion of a healthy diet, and rational use of fluoride, the lesion can be controlled, and
remineralization of the dental tissue may occur. As discussed in Chap. 6, this is true
for non-cavitated carious lesions and even for cavitated ones, as long as the patient
is able to clean the lesion properly on a regular basis. However, in the presence of a
cavity with no possibility of biofilm control inside it, the lesion is likely to progress,
and the appropriate treatment is the placement of a restoration. Early management
of deep carious lesions can arrest demineralization and reduce the need for pulp
therapies. This chapter will guide the reader in the management of deep dentin cari-
ous lesions in the aim of improving patients’ health.

10.2 Dental Caries Lesion Development and Pulp Reactions

Dental caries results from an interaction between the microbial biofilm and the min-
eralized dental tissues. Imbalance between the physiological processes of deminer-
alization and remineralization with predominance of demineralization events will
cause mineral loss from dental tissues with consequent formation of the cari-
ous lesion.
As thoroughly described in Chap. 6, the first stage of carious lesion development
involves erosion and porosity of the enamel surface. A subsurface lesion is formed
just below the enamel, and if no treatment is provided and the disease continues,
increased porosity of the outer surface is established, with an increased subsurface
demineralization. This can lead to the formation of a cavity, which first reaches the
enamel and then the dentin on the coronal part of the tooth (or the cement and the
dentin in the tooth root) and, finally, leads to the total destruction of the tooth.
Very early in the carious process, due to the porosity of the enamel, stimuli from
the oral cavity pass through this tissue into the dentin. Dentin and pulp can be con-
sidered one entity, as odontoblast processes pass through the dentinal tubules. As
bacterial acid, plaque metabolic sub-products, and bacteria wall components such
as liposaccharides reach the dentin-pulp organ, different reactions can occur [2, 3].
The first alteration is the hypermineralization of the dentin just below the enamel
lesion even before the demineralization reaches the dentin. First, a secretion of
highly mineralized peritubular dentin is observed, which will reduce the diameter of
the tubule. Intratubular deposits of mineral also take place [4]. Enamel demineral-
ization takes place in the affected hypermineralized dentin. The first indications of
cellular reactions are noted in active lesions involving about 1/4 of the enamel layer,
but without discernible alterations in dentin mineralization [5].
10 Management of Deep Dentin Carious Lesions: A Contemporary Approach… 129

Bacterial products diffuse through the dentinal tubules and may induce inflam-
matory response from the pulp even before it is exposed. The inflammatory process
initiates already in the presence of non-cavitated enamel lesion [6] and intensifies as
the demineralization reaches the dentin. During dentin demineralization, a series of
products that have been trapped in the dentin during its mineralization are released.
The pulp responds to the microbial product invasion, through the permeable tissue,
liberating or activating mediators form polymorphonuclear and mononuclear leuko-
cytes. Dentin-pulp complex permeability is likely to be reduced in carious teeth due
to tubular sclerosis subjacent to the carious dentin.
Growth factors released during dentin demineralization could be related to ter-
tiary dentin formation, which seems to occur when the demineralization reaches the
dentin. Tertiary dentin formation is another form of pulp protection organized by
pulp cells in response to caries’ advance. The structure of tertiary dentin depends on
lesion activity, i.e., on the severity of the irritating stimuli, and can be divided into
two types: reactionary dentin, formed by the odontoblasts present in slow progres-
sion lesions (in mild irritation), and reparative dentin, formed by the odontoblast-­
like cells that differentiate from pulp stem/progenitor cells after the death of the
odontoblasts (in severe irritation) [7]. The faster the progression of the lesion, the
more irregular the structure of the newly formed tertiary dentin is, even with cellular
inclusion. At this stage, lesion progression can be controlled, and the inflammation
can subside, if the biofilm is regularly removed or the cavity is isolated from the oral
environment by a restoration. However, when bacteria reach the tertiary dentin, the
number of inflammatory cells is abundant. At this stage, usually severe pulp inflam-
mation occurs, with decreased healing chances. Areas of necrosis in the pulp are not
seen until the microorganisms reach the pulp [8]. The management of deep carious
lesion is linked to the inflammatory pattern of the pulp.

10.3 Different Stages of Dental Caries Lesions, Dental Tissue

Bacterial Invasion, and Lesion Control

For many decades, the decision between a conservative treatment and an invasive
treatment for dental caries lesions was related to the presence of microorganisms
inside the dental tissue. Control of non-cavitated lesions without the necessity of
restorations is well established since the 1980s [9], and it was also supported by the
traditional understanding that non-cavitated lesions harbored no bacteria and there-
fore could be controlled with no tissue removal. On the other hand, once a cavity
was formed and microorganism was present inside the dental tissue, this contami-
nated tissue had to be removed and a restoration be placed to control lesion progres-
sion. Notwithstanding, studies showed the presence of microorganisms even in
non-cavitated lesions, in both enamel [10] and dentinal tubules [11], which does not
prevent lesion arrestment. In addition, despite the great amount of microorganisms
invading the dentin tissue once a cavity is formed, Anderson, already in 1938,
showed that cavitated lesions of molars can be arrested once the biofilm is removed
[12]. Another body of evidence that dentin caries can be controlled with no invasive
130 M. Maltz et al.

therapy is the root lesions. With the increased tooth retention currently observed in
the adult and elderly population, a large number of arrested cavitated root lesions
have been observed. In addition to this evidence derived from observational data,
intervention studies also showed the possibility of arresting root carious lesions by
adopting noninvasive therapies [13]. All this evidence shows that (1) the presence of
microorganism within the dental tissue does not prevent lesion control and (2) cari-
ous lesions can be controlled once the external biofilm is regularly removed, inde-
pendent of the microorganism invasion of the dental tissues.
Despite this knowledge, the elimination of carious dentin was considered essen-
tial to control the carious process for many decades. Traditionally, it was recom-
mended to remove “all the carious tissue” prior to the placement of a restoration,
until reaching dentin with clinical characteristics similar to those of healthy tissue
in terms of hardness and staining. As early as 1908, when devising a logical sequence
of procedures for the cavity preparation, Black [14] suggested that the cavity would
be adequately clean and ready to receive the restorative material when it presented
sufficient probing resistance to promote the “dentin scream,” in addition to color
similar to sound dentin.
Later studies from the 1950s and 1960s have already shown that the removal of
carious tissue based on hardness criteria does not eliminate microbial contamination
and that there is no relationship between tissue hardness and its level of contamina-
tion. Macgregor, Marsland, and Batty [15], when evaluating bacterial growth after
total removal of softened dentin, showed that 51% of the evaluated teeth presented
viable bacterial colonies. Whitehead, Macgregor, and Marsland [16], using the
same methodology, demonstrated that the dentin, although hard, presented micro-
bial growth in 75.5% of the primary teeth and 49.5% of the permanent teeth.
Similarly, Shovelton [17] observed histologically that 36% of teeth with hard dentin
had microbial contamination, while 39% of cases with leathery dentin and 28% of
teeth with soft dentin were free of microorganisms. Using a molecular biology tech-
nique called in situ hybridization, Banerjee et al. [18] quantified the total population
of viable bacteria in different dentin layers at different depths (superficial, medium,
and advanced – the latter corresponding to the hard dentin usually kept after cavity
preparation). Many microorganisms were found at all depths, including the dentin
layer considered healthy. This reinforces the absence of association between the
clinical aspect and level of contamination.
These results allow us to infer that the maintenance of bacteria under the restora-
tion, which routinely occurs in dental practice, does not cause clinical failure. This
knowledge gave rise to conservative treatment strategies for carious lesions of dif-
ferent depths, freeing the dentist from the obligation to remove all the carious dentin
as a fundamental premise for treatment success.
Sealing carious lesion forms a physical barrier and cuts off the nutrients from the
oral cavity to the cariogenic microorganisms. Studies on sealing carious tissue
under sealants or restorations have shown reduction or complete elimination of the
population of viable microorganisms [19–26], thus controlling caries progression.
A clinical study compared the microbiological infection (in culture) immediately
after conventional carious dentin removal and a conservative caries removal with
10 Management of Deep Dentin Carious Lesions: A Contemporary Approach… 131

sealing of carious dentin for six months. Significantly less anaerobic bacteria, aero-
bic bacteria, and Streptococcus mutans growth was observed after sealing carious
dentin than after traditional dentin caries removal [27].
Based on the abovementioned studies, it can be concluded that:

• Microorganisms invade the dental tissue already in non-cavitated lesions.

• Microorganisms within the dental tissue (either enamel or dentin) do not pre-
clude lesion arrestment, as long as it is possible to control the external biofilm.
• When it is not possible to control lesion progression through biofilm control,
sealing carious lesions or placing a restoration is necessary, depending on
lesion depth.
• There is no relationship between dentin hardness and level of bacterial
contamination.
• The traditional methods of carious dentin removal usually leave microorganisms
within the hard dental tissue left at the bottom of the cavity preparation before
restoration.
• It is not necessary to remove all carious dentin before the restoration is placed
because, over time, sealing of carious dentin results in lower levels of infection
than traditional dentin caries removal.

10.4 Treatment Options for Deep Dentin Carious Lesions

The traditional approach for the management of deep carious lesions was based on
complete (or nonselective) caries removal, which results in a higher risk of pulp
exposure, as widely demonstrated in the literature [20, 28–30]. Regardless of the
dentition, whether primary or permanent, regardless of the study design, random-
ized trials or not, studies are unanimous in demonstrating that this strategy results in
a higher risk of pulp exposure in comparison with less invasive techniques. Indeed,
recent consensus reports have stated that complete or nonselective caries removal is
no longer recommended; it is considered overtreatment according to current con-
cepts for caries removal [31, 32]. The recent systematic review with meta-analysis
by Schwendicke et al. [33] concluded that less failures were observed for conserva-
tive techniques based on selective caries removal or no caries removal in compari-
son with nonselective caries removal, for both primary and permanent dentition.
In an attempt to avoid pulp exposure, different treatment strategies have been
proposed over the last decades for the clinical management of deep carious lesions.
Several investigations in the last century have already demonstrated that decayed
dentin could be retained so that pulpal exposure could be avoided during cavity
preparation [34, 35]. The treatment, called indirect pulp capping (IPC), performed
mainly on primary teeth, is based on excavating decayed dentin as much as possible
without pulp exposure. In this technique, only a thin layer of carious dentin is left
over the pulp. Microbiological studies showed that, although the deep layer of resid-
ual carious dentin left during IPC is almost always contaminated, this layer was
either rendered sterile or the number of microorganisms was greatly reduced after
132 M. Maltz et al.

sealing [36]. More recently, however, the European Organization of Endodontology

defined IPC as a therapy that leaves neither soft nor firm carious dentin behind [37].
The most conventional option for the conservative management of deep carious
lesions is the stepwise excavation (SW) technique, currently seen as selective caries
removal to firm dentin (SCR-FD) in two visits. In this approach, only the necrotic
layer of carious dentin is removed from the pulpal/axial cavity walls at the first visit,
during the acute phase of caries progression (this stage is currently called selective
caries removal to soft dentin [SCR-SD]), followed by cavity lining with calcium
hydroxide cement, glass ionomer cement, or hydraulic calcium silicate cement and
temporary restoration [37]. In the second visit, SCR-FD is performed, and a restora-
tion of long-lasting material is placed. The aim of the first stage is to change the
cariogenic environment, replacing an active carious environment, clinically identi-
fied by a soft, discolored, and wet tissue, by an arrested carious environment, char-
acterized by a darker, harder, and drier appearance [3, 37]. From a clinical/practical
perspective, the reasoning behind this technique is that after a given time, the dentist
will be able to reach firm dentin with no/lower risk of pulp exposure. Studies com-
paring SW with nonselective caries removal have shown that the two-step procedure
significantly reduces the risk of pulp exposure [20, 28–30, 37]. The most robust
evidence on this topic was generated by a 5-year randomized clinical trial that
showed 60.2% of success for SW compared with 46.3% success for nonselective
caries removal to hard dentin (P = 0.03) when pulp exposures per se were included
as failures. Non-exposed pulp of teeth submitted to conventional dentin caries
removal was 50% (95% CI = 1.01 to 2.2, P = 0.04) more likely to fail than the
SW-treated teeth. In general, SW was superior to nonselective caries removal, with
less pulpal exposure, less pain and more teeth with vital pulps in the SW group [38].
The clinical changes that occur in sealed carious dentin after the first session of
SW led to questioning the need for reopening the cavity for final excavation and
gave rise to a series of studies on this topic. Several studies using different method-
ologies have assessed the effect of sealing carious dentin, in both shallow and deep
lesions. These studies may be categorized according to the outcome under investi-
gation into:

• Clinical evidence: replacement of softened and yellowish tissue by harder and

darker dentin after cavity sealing, both in shallow [39–41] and deep [20, 24, 26,
42–45] carious lesions (Fig. 10.1)
• Laboratorial evidence: increased hardness perceived in tactile inspection of
sealed carious dentin confirmed by microhardness analyses performed on exfoli-
ated primary teeth [46, 47]
• Biochemical evidence: increased mineral content after sealing carious dentin,
with higher levels of calcium [43] and phosphorus [48]
• Radiographic evidence: increased radiopacity in the radiolucent zone beneath
the restoration [24, 49] (Fig. 10.2)
• Structural evidence: structural reorganization of sealed carious dentin, with total
or partial obliteration of dentinal tubules observed by scanning electron micros-
copy analyses [43, 50] (Fig. 10.3)
10 Management of Deep Dentin Carious Lesions: A Contemporary Approach… 133

a b

Fig. 10.1 Carious lesion immediately after SCR-SD, with a softened and yellowish tissue (a);
clinical aspect after 6 months of cavity sealing, with a harder and darker tissue (b)

a b e

c d

Fig. 10.2 Tooth treated with SCR-SD. Bitewing radiographs taken at baseline (a), after
6–7 months (b), 3 years (c), and 10 years (d). The 10-year follow-up periapical radiograph shows
a normal periapical area (e). Increased radiopacity of the carious dentin left beneath the restoration
can be observed [49]
134 M. Maltz et al.

a b

Fig. 10.3 Scanning electron microscopy photomicrographs (×3000) of dentin samples.

Disorganized dentin structure with exposure of inter-tubular dentin collagen fiber and bacterial
infection after SCR-SD (a); more organized dentin with total or partial obliteration of dentinal
tubules and a reduction in bacterial infection after a 3-month sealing period with wax (b) [44]

• Microbiological evidence (quantitative assessment): reduction in the number of

viable bacteria when the caries lesion was isolated from the external environ-
ment, either through the use of sealants or restorations [20–26, 36, 39–44, 50–
52], achieving lower levels of infection than traditional dentin caries removal [27]
• Microbiological evidence (qualitative assessment): changes in the composition
of the microflora, with less complex and less cariogenic microbiota after sealing
[52, 53]

In addition to this body of evidence supporting the SCR-SD as a one-visit tech-

nique, some disadvantages of the two-visit procedure (associated with the need for
a second visit to complete the treatment) also became evident:

• Additional cost [54–57], time, and discomfort to the patient.

• Possibility of pulp exposure during the final excavation, around 15–17.5%
[28–30].
• Risk of patient absenteeism in the second visit, leading to fracture or loss of
temporary filling and, consequently, lesion progression [58–60].

Based on all this evidence, it became clear that once carious dentin is isolated
from the nutrient supply, deep carious lesions can be managed by SCR-SD. Considering
10 Management of Deep Dentin Carious Lesions: A Contemporary Approach… 135

a b

c d e

Fig. 10.4 Clinical and radiographic images of SCR-SD in a primary tooth. Periapical radiograph
of tooth 75 with radiolucent image extending to the inner half of dentin (a). Radiographic aspect
after cavity restoration (b). Clinically, the lesion presents as a large cavitated lesion (c). Clinical
aspects of the cavity after nonselective removal of carious tissue from the surrounding walls and
SCR-SD at the pulpal wall (d). Composite resin restoration (e)

that an effective isolation from the nutrient supply is only achieved by adequate mar-
ginal sealing of the cavity, it is worth mentioning that the peripheral/lateral walls of
the cavity must be excavated to hard dentin. Therefore, SCR-SD should be restricted
to the pulpal/axial walls of the cavity (Figs. 10.4 and 10.5).
Before the publication of recent consensus reports [31, 32] this technique was
also known as partial, incomplete, minimally invasive, or ultraconservative caries
removal. For standardization purposes, the current terminology used in the literature
for caries removal techniques was adopted in the present chapter.
136 M. Maltz et al.

a b

c d e

Fig. 10.5 Clinical and radiographic images of SCR-SD in a permanent tooth. Bitewing radio-
graph of tooth 46 with radiolucent image extending to the inner half of the dentin (a). Clinically,
the lesion appeared as an underlying dentin shadow on the mesial portion of the tooth (b). Complete
removal of carious tissue from the surrounding walls (c) and SCR-SD at the pulp wall using a hand
excavator (d). Final appearance of the cavity after SCR-SD (e). Images are courtesy of MSc Rafael
Schultz de Azambuja

10.5 Clinical Evidence for Primary Teeth

Clinical studies assessing the effectiveness of SCR-SD are usually focused on two
different outcomes: maintenance of pulp vitality and restoration longevity.
Regarding the maintenance of pulp vitality, similar success rates were found for
SCR-SD (92%) and nonselective caries removal (96%) [61] after 24 months of
monitoring. This study also showed that the operative time was significantly higher
for nonselective excavation, which is an important aspect to be considered – mainly
during the treatment of children. This study was recently corroborated by a multi-
center randomized clinical trial that also compared the SCR-SD technique with
nonselective caries removal and found high (≥96.5%) success rates for both strate-
gies, with no difference between them [62]. In a series of studies performed at the
Federal University of Rio Grande do Sul, the success rate of SCR-SD in primary
molars ranged from 79% to 96% after follow-up periods from 2 to 5 years [63–68].
Another possible concern related to the SCR-SD technique that has motivated
some studies in this research field is the risk of reduced restoration longevity due to
the maintenance of decayed tissue beneath the restoration. A systematic review with
meta-analysis on this topic that included four studies found that SCR-SD increased
the risk of experiencing restoration failure [69]. The risk of bias of the studies
10 Management of Deep Dentin Carious Lesions: A Contemporary Approach… 137

included was classified as high, and the quality of evidence was low, which led the
authors to conclude that the evidence level was insufficient for definitive conclu-
sions. In fact, taking a closer look at the four studies included in this systematic
review, two studies assessing glass ionomer restorations have not found difference
between the study groups [70, 71], while another one detected no failure over the
study period in any of the comparison groups [72]. Therefore, there is only one
study in the literature showing lower success rates for resin restorations after
SCR-SD than after nonselective caries removal in deep carious lesions of primary
molars [61, 73]. After 24 months of follow-up, the authors found 66% of success
rates for restoration in primary molars after SCR-SD and 86% after nonselective
caries removal (p = 0.03) [61], with these rates decreasing to 57% and 81%, respec-
tively, after 36 months of monitoring (p = 0.004) [73].
Another recent randomized clinical trial compared SCR-SD and SW for the
management of deep carious lesions in primary molars [57, 74]. Similar success
rates were observed after 12 [74] and 24 months [57] regarding the primary out-
come of the study [57]. The authors concluded that the significantly higher costs for
performing the two-step procedure instead of the one-step treatment may not be
justified. It is important to mention that the International Caries Consensus
Collaboration organized by the European Organization for Caries Research has not
recommended SW for the management of deep carious lesions in primary teeth [31].

10.6 Clinical Evidence for Permanent Teeth

Studies including permanent teeth are less abundant in the literature. The pioneering
study coordinated by Maltz et al. followed patients with deep carious lesions in
permanent posterior teeth who underwent SCR-SD and resin restoration for
6–7 months [24], 14–18 months [75], 3 years [76], and 10 years [49, 77]. After 5
and 10 years of monitoring, success rates were 82% and 63%, respectively, when all
reasons for failure were combined (restoration fractures and pulp necrosis). When
the failures caused by fracture were subtracted out, success rates concerning pulp
vitality increased to 93% and 80% at 5- and 10-year recalls, respectively. This was
the first long-term evidence on SCR-SD in permanent teeth available in the litera-
ture; however, it was a single-arm clinical trial, with no comparison group.
Bearing in mind that randomized controlled clinical trials are the study design of
choice to assess the effectiveness of a given therapy, this evidence was generated
more recently. A multicenter, randomized, controlled clinical trial was conducted to
compare the effectiveness of SCR-SD and SW in individuals with deep carious
lesions (≥1/2 dentin thickness) in permanent molars [58, 78]. It is worth highlight-
ing that this study compared a technique that leaves carious tissue (SCR-SD) and a
technique that completely removes carious dentin at the second visit (SW). After
5 years of follow-up [59], success rates in terms of maintenance of pulp vitality
were 80% for SCR-SD and restoration in a single visit and 56% for SW (p < 0.05).
This low success rate observed in the SW group was mainly related to incomplete
treatments, in which the patients have not attended the second visit to receive the
138 M. Maltz et al.

final restoration. After a given period, the temporary fillings tend to fail, leading to
lesion progression and pulp damage. The comparison of SCR-SD and complete
cases of SW showed similar success rates (80% vs. 75%, p > 0.05). When it comes
to restoration longevity, the 5-year survival analysis showed similar success rates
for SCR-SD (79%) and the SW procedure (76%) [79]. These findings confirm that
maintaining decayed dentin in the pulpal/axial wall of deep cavities by adopting the
SCR-SD technique can preserve pulp vitality without damaging restoration survival
in permanent teeth during a 5-year period.
Another study comparing SCR-SD and SW for the management of deep carious
lesions (>2/3 of dentin thickness) in permanent teeth was conducted in Egypt, but
only the 1-year results have been published so far [56]. During this short-term fol-
low-­up period, the authors found similar success rates for both techniques (89.4%
for SCR-SD and 84.9% for SW). The estimated mean time free of complications
was 23 months for SCR-SD and 18 months for the SW procedure, without signifi-
cant differences between them (p > 0.05). This study also assessed the total cost of
both strategies and found a significantly higher total cost for SW than for SCR-SD
(p > 0.05).
Additional evidence on this topic was provided by a retrospective study that
evaluated the longevity of adhesive restorations performed in deep carious lesions
in young permanent molars after nonselective caries removal or SCR-SD in a uni-
versity setting [80]. The survival of restorations reached 57.9% up to the 36-month
follow-up, with no difference between the two caries removal techniques (p > 0.05).
The systematic review with meta-analysis by Schwendicke et al. [33] showed
that for deep carious lesions in permanent teeth, the odds of failure were higher for
SW than for SCR-SD (OR 2.25, 95% CI 1.33 to 3.82; 3 studies, 371 teeth; moderate-­
certainty evidence). However, no difference was observed between these two strate-
gies in the network meta-analysis on the relative effects of different interventions
for treating deep lesions.
Based on all the literature discussed in this chapter, it seems clear that there is no
evidence to support the need for cavity reopening for further excavation and that
SCR-SD may be adopted for the treatment of deep carious lesions in permanent
teeth as a single-visit approach.

10.7 Pulp Response to SCR-SD

In addition to clinical studies assessing outcomes such as pulp vitality and restora-
tion longevity, histological studies have been performed to investigate pulp and
dentin response to nonselective and selective caries removal [8, 81]. The control
(sound) teeth of these studies showed (1) no changes in the dentin/predentin/odon-
toblast complex; (2) dentinal tubules and odontoblasts layers with normal anatomy
and no tertiary dentin or other calcifications; (3) no presence of inflammatory cell
accumulations or dilated vessels in the pulp tissues; and (4) no bacteria in the cir-
cumpulpal dentin. On the other hand, teeth with deep carious lesion restored after
nonselective caries removal presented no pulp inflammation in 28/59, mild
10 Management of Deep Dentin Carious Lesions: A Contemporary Approach… 139

inflammation in 14/59, and irreversible inflammation in 17/59. Regarding the teeth

treated with SCR, although all teeth presented inflammation (8/8 [81] and 12/12
[8]), the authors found that: (1) teeth presented no symptomatology and responded
within normal limits to thermal and electric tests [8, 81]; (2) teeth presented mild
inflammation, with no case of moderate or severe inflammation [8]; (3) tertiary
dentin was present in all teeth [8]; (4) bacteria were present in dentin adjacent to
the cavity, in the transition between the secondary and the tertiary dentin and, in
some cases, in the superficial tertiary dentin [8, 81]. Based on these results, it is
possible to conclude that the risk of pulp inflammation is observed with both non-
selective and selective caries removal techniques. In addition, it is important to
highlight that while almost 30% of teeth treated with nonselective excavation
underwent irreversible inflammation and consequently the need for more invasive
treatments, no similar cases occurred after SCR. Furthermore, the above-described
clinical studies show that less invasive approaches such as SCR-SD may improve
patient-relevant clinical outcomes.

10.8 The Role of Cavity Liners After SCR-SD

Cavity liners have been traditionally proposed during the management of deep cari-
ous lesions due to several reasons: to reduce the level of contamination, induce ter-
tiary dentin deposition, remineralize demineralized tissues, act as thermal or electric
insulator, and protect pulpal cells against irritation stimuli derived from adhesives
[82, 83]. Among the used materials, calcium hydroxide cement (CHC), glass iono-
mer cement (GIC), and hydraulic calcium silicate cements have been used in the
clinical practice when the pulpal/axial cavity walls are close to the pulp.
During the decades when decayed tissue was excavated as much as possible and
only a thin layer of carious dentin was left over the pulp to avoid its exposure, cavity
lining was seen as an essential clinical step during the management of deep carious
lesions. However, more recently, the literature has investigated whether the use of
cavity liners plays a vital role on pulpal outcomes when applied to deep lesions after
conservative caries excavation techniques.
Although the European Society of Endodontology (2019) [37] recommends the
use of hydraulic calcium silicate or glass-ionomer cement over the deep dentin in
both treatment strategies advocated for the management of deep lesions (SCR-SD
and SW), the need for cavity lining in maintaining pulpal vitality has been ques-
tioned. A systematic review with meta-analysis by da Rosa et al. [84] investigated
whether the use of CHC liner improves the clinical success in the treatment of deep
carious lesions. A total of 17 studies were included, of which 15 were conducted in
primary dentition and 2 in permanent dentition. Meta-analyses were performed to
compare CHC with GIC (data derived from two studies in primary teeth) and CHC
with adhesive (data derived from four studies in primary teeth), and no significant
differences were observed. The authors concluded that the use of CHC as a cavity
liner did not influence the clinical success of treatment for deep lesions; however,
the evidence was of moderate to very low quality.
140 M. Maltz et al.

Regarding permanent teeth, the only two studies included in this systematic
review [44, 85] reported short-term outcomes (3–4 months of follow-up), and no
meta-analysis was performed. Corralo et al. [44] compared lining with CHC, GIC,
and an inert material (wax) and found no difference among the tested materials
regarding dentin hardening, obliteration of dentinal tubules, decreasing bacterial
numbers, and dentin reorganization after 3–4 months of sealing. Pereira et al. [85]
compared teeth with and without CHC lining in conjunction with resin-modified
GIC restorations. Irrespective of CHC liner use, no difference was found regarding
tooth vitality, dentin darkening, hardening, and decreasing contamination after
3 months. Another short-term study not included in the cited systematic review
compared the lining with GIC and an inert material for 2 months [86]. The authors
found enhanced calcium and phosphorus levels and a better-organized tissue with a
more compact intertubular dentin in both groups. They concluded that caries arrest-
ment with dentin reorganization occurs regardless of the lining material placed in
contact with the infected dentin.
No long-term study has been performed on permanent teeth. A randomized clini-
cal trial comparing the use of CHC, resin-modified GIC, and adhesive system after
SCR-SD reported the 12-month results [87]. Success rates regarding the mainte-
nance of pulp vitality were 96.8%, 96.5%, and 94.6% for CHC, resin-modified GIC,
and adhesive, respectively, with no significant difference among groups (P = 0.81).
A randomized clinical trial, performed by our research group at the Federal
University of Rio Grande do Sul, evaluated the effectiveness of indirect pulp protec-
tion with CHC or universal adhesive in deep carious lesions after SCR-SD or
SW. Over 18 months of monitoring, similar success rates regarding the maintenance
of pulp vitality were found (95.5% for CHC and 99.1% for adhesive) (unpub-
lished data).
Lining with CHC has been also compared with mineral trioxide aggregate (MTA)
in a randomized clinical trial [88, 89]. Similar success rates were found regarding
the maintenance of pulp vitality at the 2-year follow-up (91.7% for CHC and 96.0%
for MTA) and at the 4-year follow-up (82.9% for CHC and 86% for MTA).
Based on the available literature on this topic, the adequate cavity sealing is
responsible for bacterial reduction and lesion control after SCR-SD. The remaining
carious dentin has been seen, itself, as a protective factor for pulp vitality in deep
carious lesions. Therefore, using cavity liners does not seem to be important when
using conservative caries removal techniques [84, 90, 91].

10.9 Future Perspectives for the Management of Deep

Carious Lesions

Current understanding of pulp biology and the pulp response to the release of
dentin-­bound bioactive growth factors demonstrate that the pulp has a greater regen-
erative capacity than previously thought [92]. Preserving all or part of the pulp is
beneficial, resulting in a less invasive treatment than conventional endodontic
10 Management of Deep Dentin Carious Lesions: A Contemporary Approach… 141

treatment [93], which, in addition to being specialized and costly, removes tooth
structure, weakening the tooth.
Pulp preservation or the choice between invasive or more conservative treatment
for deep carious lesions depends on the pulpal diagnosis of reversible and irrevers-
ible pulpitis, i.e., on the inflammatory status of the pulp. Correlations between his-
tological findings and clinical signs and symptoms have been used to differentiate
between stages of reversible and irreversible pulpitis despite limitations [3].
Traditionally, a reversible pulpitis should be treated with a conservative treatment,
whereas an irreversible pulpitis should be treated with pulpectomy or tooth extrac-
tion [3, 81]. In the same line, Wolters et al. [94] proposed a classification of pulp
inflammatory processes with treatment indications:

1. Mild/reversible pulpitis: positive response to the thermal sensitivity test

(−20 °C), lasting up to 20 s, with possible sensitivity to vertical and horizontal
percussion, but there is no previous history of spontaneous pain. The proposed
treatment for these cases is indirect pulp therapy, which provides SCR-SD as a
counterpoint to conventional pulpotomy therapy or root canal treatment.
2. Moderate/irreversible pulpitis: symptoms are prolonged response to the thermal
test (−20 °C), which can last for minutes, sensitivity to percussion, and presence
of spontaneous pain that can be suppressed with pain medication. This may or
may not present with thickening of the space of the periodontal ligament and is
described as extensive local inflammation confined to the coronary pulp. The
therapy indicated for these cases is coronal pulpotomy.

Despite these traditional treatment indications, preliminary investigations have

suggested that pulp preservation is possible when vital pulp therapies (such as
SCR-SD, IPC, or pulpotomy) are performed in symptomatic teeth [95–98]. Clinical
case reports have shown that in some situations of moderate/irreversible pulpitis,
where the pulp is conventionally diagnosed as having irreversible inflammation, it
can be maintained with clinical and radiographic success [95, 96, 99]. Results of a
clinical study by Asgary et al. [93] indicated that vital teeth can be treated with
SCR-SD irrespective of the presence of signs and symptoms of pulpitis (mild or
moderate). After 1 year of follow-up, the success rates for SCR-SD, direct pulp cap-
ping, and partial and total pulpotomy were 95.6%, 88.5%, 85.6%, and 88.7%,
respectively, with no statistical difference among groups.
It is important to point out that SCR-SD is a well-established technique for the
management of deep carious lesions in teeth with signs and symptoms indicatives
of pulp vitality, such as the absence of spontaneous pain, positive response to the
cold test, and negative response to percussion, in addition to a periapical radiograph
suggesting no pulpal involvement. However, these recent studies including teeth
with signs of irreversible pulpal inflammation shed light on this research field.
Further studies, mainly long-term randomized clinical trials may broaden the indi-
cations of the SCR-SD in the future.
142 M. Maltz et al.

10.10 Concluding Remarks

Based on the aspects discussed along this chapter, it is possible to summarize the
contemporary approach for the management of deep dentin carious lesions in pri-
mary and young permanent teeth as follows:

• Nonselective caries removal results in a high risk of pulp exposure and is consid-
ered overtreatment according to current concepts for caries removal.
• Selective caries removal to soft dentin as a single-visit approach is recommended
for the management of deep carious lesions in both primary and permanent dentition.
• There is no reason to reopen the cavity to excavate further, thus eliminating the
disadvantages of the stepwise excavation technique related to the need for a sec-
ond visit.
• The use of a cavity liner after selective caries removal, while not harmful, seems
to be an unnecessary clinical step.

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Bioactive Ceramics for Pediatric
Dentistry 11
Carolyn Primus

Contents
11.1 Bioceramics 150
11.2 Bioactive Ceramics and Biomineralization 151
11.3 Bioactive Ceramic Cements 154
11.4 Bioactive Cement Compounds 156
11.5 Cement Hydration Reactions 158
11.6 Pediatric Bioactive Ceramic Dental Cements 160
11.6.1 Indications 164
11.6.2 Composition 164
11.6.3 Radiopacity 166
11.6.4 Pastes and Resins 166
11.6.5 Format 167
11.6.6 Packaging Materials 175
11.7 Cement Product Characteristics 176
11.7.1 Handling 176
11.7.2 Setting Time 177
11.7.3 Solubility 178
11.7.4 Dimensional Stability 179
11.7.5 Bonding 179
11.7.6 Strength 180
11.7.7 Costs 180
11.7.8 Other “Bioactive” Materials 181
11.8 Summary 181
References 182

C. Primus (*)
Dental College of GA, Augusta University, Sarasota, FL, USA

© The Author(s), under exclusive license to Springer Nature Switzerland AG 2023 149
A. B. Fuks et al. (eds.), Contemporary Endodontics for Children and
Adolescents, https://doi.org/10.1007/978-3-031-23980-9_11
150 C. Primus

11.1 Bioceramics

Our world is comprised of substances that are organic, metallic, ceramic, or combi-
nations thereof, as depicted in Fig. 11.1. Organic materials have carbon-hydrogen
bonds (C-H), which include monomers, polymers, and many other organic com-
pounds; metals are often shiny and good conductors of heat and electricity. Ceramic
materials are those materials that are neither metallic nor organic and are often, but
not exclusively, oxide compounds. Many ceramic materials are crystalline com-
pounds, but glasses, which are amorphous (non-crystalline), are also ceramics and
are often combined with ceramic crystals. Most glasses are based on silica (silicon
dioxide, SiO2), which is distinct from silicone, an organic substance.
Biomaterials are subset of materials (Fig. 11.1) that are used in vivo. Metal,
ceramic, and organic compounds may be biomaterials, which are sometimes com-
bined. For instance, composite resin combines organic resins and ceramic filler par-
ticles. All dental restorative and prosthodontic materials are biomaterials, and many
of them are bioceramics.
Bioceramics may be bioinert, radiopaque, or bioactive (Fig. 11.2) but are best
known for being bioinert. Bioinert materials do not elicit a response from the host
and do no harm. Alumina and zirconia are examples of inert bioceramics used for
prosthodontics, implants, polishing media, and orthodontic brackets. Some bioc-
eramic powders are radiopaque (white on X-ray images), including barium sulfate,
bismuth oxide, calcium tungstate, and tantalum oxide. All glass formulas are bioc-
eramics; some glasses are inert, others are inert and radiopaque, and other formulas
are bioactive. Bioactive ceramics, the subject of this chapter, do elicit a response
in vivo.

Fig. 11.1 Categories of

materials showing the main
categories and the subset
of biomaterials

Cermet Ceramic

Bio- Compo-
Metallic site
materials

Organo-
metallic Organic
11 Bioactive Ceramics for Pediatric Dentistry 151

Inert Bioactive

• Alumina • Hydroxyapatite
• Zirconia • Calcium cements
• Most glasses • Some glasses

Inert & radiopaque

• Some glasses
• Barium sulfate
• Tantalum oxide

Fig. 11.2 Three categories of bioceramics with examples of crowns, glass fiber posts, and bone
grafting material

11.2 Bioactive Ceramics and Biomineralization

Bioactive ceramics provide benefits for healing [1], such as beneficial ion release to
stimulate new bone or dentin formation. In this chapter, a more narrow definition of
bioactivity is followed as defined by an international standard for surgical materials,
ISO 23317:2014: the in vivo formation of a calcium phosphate layer, similar to
hydroxyapatite, on the surface of the biomaterial. This international standard has an
in vitro test for bioactivity using phosphate-buffered saline. This bioactivity has also
been denoted as biomineralization. Bioactivity is not limited to biomineralization,
which is also the cellular process by which living organisms secrete inorganic min-
erals [2], but for simplicity, biomineralization is synonymous with bioactivity.
Bioactive ceramics, in this context, have two key characteristics: they create a high
pH by releasing hydroxide ions, and they release calcium ions in vivo into the body
fluids. Body fluids, being supersaturated in phosphate ions, react near the surface of
the ceramic where the pH is high, and precipitate a hydroxyapatite-type
(Ca10(PO4)6(OH)2) layer on the surface of the ceramic, as expressed in Eq. 11.1.

10Ca +2 + 6PO 4−4 + 2OH − → Ca10 ( PO 4 )6 ( OH )2 (11.1)

[calcium ions + phosphate ions + hydroxide ions] in solution → hydroxyapatite pre-
cipitate [crystals].
This precipitation reaction occurs acellularly when bioactive ceramics are placed
in simulated body fluid, in vitro [3] and in vivo [4]. The precipitated layer may begin
as an amorphous calcium phosphate and transform over time to poorly crystalline,
152 C. Primus

β-type carbonated apatite crystals. The ratio of calcium to phosphate may be lower
than 1.67, the ratio in bone. The layer is self-limiting, because when the hydroxy-
apatite (HA) layer thickens, ion diffusion from the bioactive ceramic is inhibited.
When the hydroxyapatite precipitate is formed, the surface of the bioceramic is
hidden from the body’s immune system and reduces the “foreign body” reaction by
which the body identifies, attacks, and attempts to destroy (resorb) the ceramic. The
formation of the HA layer precedes a cascade of healing reactions [5, 6] of the pulp
or alveolar bone, which are not described in this chapter.
Only a small subset of bioceramics are bioactive, including certain silicate
glasses (often denoted as bioglasses), calcium hydroxide, hydroxyapatite, other cal-
cium phosphates, calcium silicate cement, and calcium aluminate cement. The
focus of this chapter is on calcium silicate and calcium aluminate cements. These
unique cement powders react with water to harden and cause this bioactive reaction
in Eq. 11.1.
“Bioactive glasses” were first invented by Hench [7, 8] and contained silica,
calcium, and phosphorous oxide but now include similar glasses with magnesium
oxide [9] and boron oxide [10] as components. Some bioactive glasses are a com-
ponent of alveolar bone grafting materials [11] where a coarse (~100 μm) glass
powder is implanted, such as in an extraction socket [12]. Bioactive glass and other
bone graft materials release ions into the tissue fluids and are slowly replaced by
advancing bone tissue. Bone grafting materials rely on micro-, meso- or macropo-
rosity, and their coarse particles serve as bone cell scaffolds [13] for gradual disso-
lution and resorption of the glass. Both crystalline hydroxyapatite grafting materials
and bioactive glass particles are resorbable.
Calcium hydroxide has long been used in dentistry as an antimicrobial [14]
medicament that is biomineralizing and stimulates reparative dentin [15].
However, calcium hydroxide is not the best material for pulpotomies for primary
teeth, because the histological response has been formation of a deficient, porous
reparative dentin [16, 17]. Calcium hydroxide particles gradually form calcium
carbonate, which is a bioinert ceramic. Calcium hydroxide is not a cement (it
doesn’t set nor form a hard layer), unless combined with other substances, such as
the resins in Dycal.
Calcium phosphate cements were invented by Chow [18] and are self-setting,
bioactive ceramics. Calcium phosphate compounds react to form HA. That is, tetra-
calcium phosphate, dicalcium phosphate, and dicalcium phosphate dihydrate can
gradually dissolve under neutral pH conditions and precipitate HA, amorphous cal-
cium phosphate, or brushite, via self-setting reactions to form a hard mass. The
magnesium phosphate cements [19] are similar and are also biomineralizing/bioac-
tive. These cements form HA but are generally slow to set and are considered weak.
The calcium silicate and calcium aluminate cements differ from the bioactive
glasses, hydroxyapatite, calcium hydroxide, and calcium phosphate cements. These
11 Bioactive Ceramics for Pediatric Dentistry 153

calcium cements form a solid mass (set) by reaction with water; that is, they are
hydraulic, like calcium phosphate cements. Calcium silicate and calcium aluminate
cements are not currently designed to have pores for osseous ingrowth or resorption,
unlike the bioactive glasses or calcium phosphate cements; therefore, these solidi-
fied cements are usually not resorbable or dissolvable. The cements set within min-
utes to hours and are bioactive. (See Fig. 11.3 for an ex vivo example showing a
hydroxyapatite (HA) layer formed on a calcium silicate cement that had been placed
in a root-end filling, soaked in phosphate-buffered saline, and then sagittally sec-
tioned.) The calcium silicate/aluminate cements begin to biomineralize (form HA)
acellularly within 30 min. The clinical and histological responses to the calcium
silicate/aluminate cements are equal to, or superior to calcium hydroxide [17, 20,
21], perhaps because the cements set and form a matrix and reservoir of hydroxide
and calcium ions. This is different from a non-setting paste of calcium hydroxide, a
resin cement containing calcium hydroxide, or so-called bioactive resin-modified
glass ionomers.
In the last three decades, bioactive calcium silicate and calcium aluminate
cements have achieved prominence in pediatric dentistry and endodontics for vital
pulp and periapical tissue therapy. This chapter introduces the reader to the unique
and beneficial characteristics of bioactive calcium silicate and calcium aluminate
cements, explaining the setting reactions, and comparing the dental materials avail-
able for pediatric dentistry. From this information, pediatric dentists may make
more informed choices for their benefit and the oral health of their patients.

Fig. 11.3
Biomineralization layer
(white) on gray calcium
silicate cement used in
root-end filling. This tooth
was filled, soaked in
phosphate-­buffered saline,
and then sectioned
154 C. Primus

11.3 Bioactive Ceramic Cements

Dental cements include materials to coronally affix prosthodontic or orthodontic

devices, either adhesively or via luting (non-adhesive). Dental cements are also used
to line a cavity or create an insulating base under a restorative material. The term
dental cement is also used for materials that seal root canals with gutta percha.
Many compositions of “cements” are used, including the traditional zinc oxide-­
based cements (phosphate, carboxylate, and eugenolate), glass ionomer, and com-
posite resins. Such cements usually rely on acid-base reactions, and they do contain
bioceramic powders but are not bioactive. In this chapter, we focus on the bioactive
calcium silicate and aluminate cements that require water for setting and are used in
endodontic therapy.
The word “hydraulic” has two meanings: exertion of a uniform pressure by a
liquid and materials that set (harden) with water. Hydraulic cements refer to the
water-setting ceramics, especially calcium silicate and calcium aluminate composi-
tions. Many non-scientific terms have been used to describe these hydraulic bioac-
tive ceramic cements including mineral trioxide aggregate (MTA), MTA-type
materials, tri-/dicalcium silicate-based material/cement, ordinary hydraulic silicate
cements, HSC, Portland cement, OPC, PC, calcium silicate cement (CSC), hydrau-
lic cements, hydraulic calcium silicate cement (HCSC), biosilicate, calcium silicate,
calcium aluminate, bioceramic cement, BC, and bioactive cement/sealer. Dental
product trade names for these bioactive bioceramics often include “MTA,” of which
ProRoot MTA was the first. Other prominent trade names in this category include
Biodentine®, EndoSequence® BC, iRoot®, NeoPUTTY®, MTA Plus®, ProRoot®
MTA, and TotalFill® BC.
The earliest publication on calcium silicate cement in dentistry dates from 1878
when Dr. Witte of Germany filled root canals with a locally made, pulverized
Portland cement [22]. Portland cement was a new invention at this time. He mixed
the cement powder with water and carbolic acid or creosote and filled 25 teeth, with
no failures after 1 year. No other mention of using Portland cement in dentistry is
known until the twentieth century. Professor Torabinejad at Loma Linda University
in California disclosed using Portland cement for dentistry in 1993, based on a spe-
cific construction-grade Portland cement that he blended with bismuth oxide pow-
der. Dr. Torabinejad used his calcium silicate cement mixture for endodontic surgery
[23] and perforations [24], which were two indications which had been especially
problematic for healing. He dubbed his mixture “mineral trioxide aggregate” (MTA)
[25] and received a patent with his co-inventor patient, who was an expert in
construction-­grade Portland cement. The cement of their invention included about
5% iron oxide, which gave the cement a very dark color. His dark-gray, patented
composition was commercialized by Dentsply Sirona (USA) in 1997, who manu-
factured it as ProRoot® MTA. The commercial dental version was a purer, finer
powder than the original prototype material from Dr. Torabinejad, having been
manufactured by following ISO 13485 and FDA good manufacturing practices.
That is, ProRoot MTA did not have the impurities inherent in most construction-­
grade cements, commonly arsenic, which is restricted (<2 ppm soluble As) in
11 Bioactive Ceramics for Pediatric Dentistry 155

dentistry. Portland cement is the term used to describe construction-grade, calcium

silicate cement and is inappropriate for dental materials, and is not used in this chap-
ter to describe the dental materials. After the gray ProRoot MTA, product, a white
version was commercialized and is often denoted as “white” or “tooth-colored”
ProRoot MTA in the dental literature. The key to the white ProRoot MTA was
reduction of the iron oxide content in the cement. Both ProRoot products were cal-
cium silicate cements blended with bismuth oxide. The ProRoot MTA products
were quickly adopted by endodontists, based on the remarkable histological results
published for the original material [23, 26]. For instance, cementum and periodontal
ligament tissues regenerated over the calcium silicate cement root-end fillings in
animals. This healing had not been so pronounced with other root-end filling mate-
rials and was greatly appreciated, though at first of unknown mechanism.
Many similar formulas have now been marketed containing calcium silicate
cement, many having MTA in their name and other products with new trade names;
however, the early imitators of ProRoot MTA all contained calcium silicate cement.
In general, the products contain calcium silicate cements of similar but not identical
formulas to the cement in ProRoot MTA and a radiopaque powder. Other radi-
opaque powders are often used, rather than bismuth oxide. Such bioactive ceramic
cements are indicated for any pulp, dentin, or alveolar bone-contacting procedure
and have become the standard of care for vital pulp therapy [27]. Pediatric dentists
use bioactive ceramic cements for pulp capping, lining or base of a cavity, pulpot-
omy, apexification, resorption, or revascularization. (See the collage of suitable
indications in Fig. 11.4, although the indications vary with the products.) Notably,
the indications are all within the dentin, not exposed to the oral cavity. This

Fig. 11.4 A collage of

Indirect Pulp Cap
indications for use of the
bioactive ceramic cements,
especially for vital pulp Direct Pulp Cap/
therapy. Cement is shown Partial Pulpotomy
in yellow
Cavity Liner/
Base

Pulpotomy/
Apexogenesis

Perforation Repair

Resorption

Sealing

Obturation/
Apexification

Root-End Filling
156 C. Primus

limitation is imposed because calcium silicate cement is vulnerable to acids. The

calcium silicate cements can be disintegrated by strong acids. Therefore, this cement
is unsuitable as a restorative material, where materials are constantly exposed to our
acidic diets, unlike the pH-neutral tissue fluids [28]. Obturation after a pulpectomy
may be suitable for immature permanent teeth or primary teeth when a successor is
absent. However, the current bioactive ceramic cement products are considered
non-resorbable and not suitable for primary tooth obturation for fear of disrupting
the eruption of the permanent teeth. Despite the versatility in Fig. 11.4 for vital pulp
therapy, high-priced bioactive cement products have prevented their universal adop-
tion in pediatric dentistry.
The calcium silicate and calcium aluminate cement powders possess properties
not found in most other dental materials. The cement powders set with water, are
dimensionally stable, release calcium ions, and form alkaline hydroxides within an
amorphous, hydrated cement matrix. Requiring moisture to set is a tremendous ben-
efit for dental applications. Lack of contraction or expansion helps seal the area of
the tooth anatomy filled with the cement, unlike other dental materials that often
shrink when they set. Most importantly, calcium silicate and calcium aluminate
cements release calcium and hydroxide ions from the surfaces of their powders, on
contact with moist tissues. These ions create bioactivity and impart antimicrobial
action on planktonic bacteria and yeast [29], although insufficient to destroy tena-
cious biofilms [30]. Calcium aluminate cements have been used in dental restorative
materials and crown cements [31, 32]. Calcium aluminate cements have greater acid
resistance than calcium silicate cements, a beneficial characteristic for their oral use
in acidic and bacterial environments [33]. The pH of the calcium aluminate cements
is not quite as high as the calcium silicate cements, but is sufficiently alkaline to
produce biomineralization and osteogenic effects [34, 35]. Calcium silicate cement
also release silicate ions, which are known to benefit osteogenesis [36], a key phe-
nomenon for healing pulpal or periapical tissue.

11.4 Bioactive Cement Compounds

Phase diagrams are used by materials scientists to understand what compounds

(phases) can be manufactured from a particular combination of components. The
compositional ranges for the calcium silicate and the calcium aluminate cements are
outlined in the partial ternary (3-component) phase diagram shown in Fig. 11.5. A
small range of composition is suitable to manufacture the calcium silicate or the
calcium aluminate cement phases. The phase diagram shows that some silica may
be dissolved in the calcium aluminate cement and some alumina can be dissolved in
the calcium silicate cement. Calcium aluminate cement compounds are chemically
separate and distinct from the calcium silicate cement region and do not overlap as
shown in Fig. 11.5; therefore, the two calcium cements (silicate and aluminate)
must be fabricated separately, but may be combined.
Calcium silicate and calcium aluminate bioactive ceramic cements are not natu-
rally occurring; high temperature manufacturing is required. To make these cements,
11 Bioactive Ceramics for Pediatric Dentistry 157

Calcium
aluminate

A3
Calcium CS a-CS cements

S2
silicate
cements
C3S2 CAS2
C3S2

a-C2S
C2S

A2S2
C3S

C2AS
C3S CA2 CA6
A

C
C3A CA

CaO C3A C12A7 CA CA2 CA6 Al2O3

Fig. 11.5 Ternary phase diagram for calcia (CaO, C), silica (SiO2, S), and alumina (Al2O3, A),
showing the compositional range for the calcium silicate (area 1) and calcium aluminate cements
(area 2)

raw materials are blended, which are ceramic powders, usually containing calcium
carbonate, silica, and alumina powders (from varied sources). The blended powders
are heated to a peak temperature of about 1500 °C in a kiln. At this high temperature,
the raw materials can quickly react to form the cement compounds. The nodules of
cement are expelled from the high temperature kiln for quick air cooling, which
ensures that the most water reactive phases of cement are maintained. The nodules of
cement are called clinker. Minor oxides, such as iron oxide, may be used to control
the cement phases and lower the firing temperature. Solution-gelation techniques are
an alternative method to manufacture the cement, generally a more expensive route.
The fired ceramic cement is ground into a fine powder and sieved via various means.
The fine cement powder is placed in a sanitary blender to disperse the cement, radi-
opaque powder, and any other additive powders evenly. The blended powders may be
packaged, or the powder may be mixed with an organic liquid into a paste for place-
ment in syringes. Researchers have speculated on the sources and techniques used
for manufacturing the dental cements; however, the compositions and methods are
proprietary trade secrets that cannot be easily discerned.
Calcium silicate and calcium aluminate cements discussed above appear to be
just two compounds. Chemically, these cements represent six hydraulic ceramic
compounds (phases). Calcium silicate cement powders for dentistry are primarily
composed of two ceramic compounds: tricalcium silicate (Ca3SiO5) and dicalcium
silicate (Ca2SiO4). These two silicates are known as alite and belite in the commer-
cial Portland cement vernacular, and haturite and larnite in the mineralogical litera-
ture, although neither are naturally occurring minerals.
158 C. Primus

Tetracalcium aluminoferrite (4CaO·Al2O3·Fe2O3, ferrite) was present in the orig-

inal ProRoot MTA, which lowers the firing temperature needed to make calcium
silicate cement. Unfortunately, tetracalcium aluminoferrite crystals are black, which
darkened teeth immediately where the overlying tissue was thin. The ferrite phase is
not considered a necessary component for these bioactive dental cements, so it has
been avoided for esthetic reasons. For instance, White ProRoot MTA has low iron
content (<1%); consequently, very little of the black ferrite phase is present.
A minor amount of alumina is often intentionally combined with silica and calcia
raw materials for making calcium silicate cement to reduce the firing temperature,
which is an economic benefit for manufacturing. When alumina is present in larger
amounts, tricalcium aluminate (Ca3Al2O6 or 3CaO.Al2O3) crystals are formed dur-
ing firing, concomitant with tri/dicalcium silicate crystals. Tricalcium aluminate is
a bioactive cement phase and is present in many of the calcium silicate dental prod-
ucts [37]. Researchers have found the aluminate phase beneficial because of its very
rapid hydration, which will accelerate cement setting. The tricalcium aluminate
cement compound can be manufactured as a separate powder for addition to cal-
cium silicate cement.
Calcium aluminate cement depicted in Fig. 11.5 is primarily composed of two
phases, calcium monoaluminate (CaO.Al2O3, calcium aluminate) and monocalcium
dialuminate (CaO.2Al2O3, calcium dialuminate), with very little silica. Tricalcium
aluminate is usually not included. These two calcium aluminate cement phases react
with water to form a hard matrix while releasing Ca+2, Al(OH)−4, and OH− ions at
the surface into the tissue fluids, to achieve the same biomineralization (HA precipi-
tation) reaction as the calcium silicate cements. Calcium aluminate cement must be
fired separately from the calcium silicate cement formulas, as depicted in Fig. 11.5,
showing separate compositional ranges.

11.5 Cement Hydration Reactions

The hydration setting reactions for the bioactive ceramic cement phases are unlike
the polymerization reactions used for many dental restoratives. The reactions occur
with water and are not catalyzed or activated, unlike light-curing, chemical-curing,
or dual-curing dental cements. The hydration reactions show how bioactivity origi-
nates. Of the cement phases, tricalcium aluminate sets the fastest, which reacts as in
Eq. 11.2.

3CaO.Al2 O3 + 6H 2 O → 3CaO. Al2 O3. 6H 2 O (11.2)

Tricalcium aluminate + water → amorphous hydrated tricalcium aluminate.
The reaction product of Eq. 11.2 is a hydrated gel of calcium aluminate. The
rapid hydration of tricalcium aluminate phase speeds setting of calcium silicate
cements; therefore, some researchers have intentionally added more tricalcium alu-
minate powder [38]. Tricalcium aluminate releases heat as it hydrates. In a tooth, the
heat is easily mitigated, and enough tissue fluid is available to continue hydration.
11 Bioactive Ceramics for Pediatric Dentistry 159

However, calcium sulfate is sometimes used to modulate the setting of the trical-
cium aluminate crystals. Calcium sulfate reacts with water and the tricalcium alu-
minate to form the intermediate product of ettringite (Ca3Al2O6.3CaSO4.32H2O) or
monosulfate (Ca3Al2O6.CaSO4.12H2O), evolving less heat. This mitigation of rapid
hardening is similar to the use of calcium sulfate dihydrate in alginate to slow its
setting time.
The ferrite cement phase also undergoes rapid hydration, as noted in Eq. 11.3.
The reaction products include a hydrated cement of calcia and alumina and release
alkaline iron hydroxide.

4CaO·Al2 O3 ·Fe 2 O3 + 19H 2 O → 2 [ 2CaO·Al2 O3 .8H 2 O ] + 2Fe ( OH )3 (11.3)

Tetracalcium aluminoferrite + water → amorphous hydrated ferrite + iron oxide
hydrate.
Calcium sulfate and calcium oxide are also used to mitigate overly fast setting of
the ferrite, similar to tricalcium aluminate. Ferrite may also form complex calcium-­
alumino-­ ferric-sulfate hydrates, such as 3CaO·(0.5Al2O3·0.5Fe2O3)·3CaSO4·32
H2O, Ca2(Al,Fe)2O5, or 4CaO·Al2O3·Fe2O3 [39].
The main hydration setting reactions for calcium silicate cement phases are
shown in Eqs. 11.4 and 11.5.

2 [ Ca 3SiO5 ] + 7 H 2 O → 3CaO. 2SiO 2. 4H 2 O + 3Ca ( OH )2 (11.4)

Tricalcium silicate (alite) + water → amorphous calcium silicate hydrate + calcium
hydroxide.

2 [ Ca 2SiO 4 ] + 5H 2 O → 3CaO. 2SiO 2. 4H 2 O + Ca ( OH )2 (11.5)

Dicalcium silicate (belite) + water → amorphous calcium silicate hydrate + cal-
cium hydroxide.
After a brief induction period, the tricalcium silicate phase hydrates, faster than
the dicalcium silicate phase. Both calcium silicate phases react to form an amor-
phous hydrated calcium silicate (3CaO.2SiO2.4H2O) concurrently releasing calcium
hydroxide, known as portlandite in cement literature and occasionally in dental lit-
erature [40]. Dicalcium silicate crystals gradually hydrate, which decreases the
porosity of the setting cement. Setting may take minutes to hours, depending on the
composition and proportions of the phases. The compressive strength increases over
about 4 weeks; however, most of the strength is developed in less than a week.
The calcium aluminate cement phases, calcium aluminate (CaO.Al2O3) and
monocalcium dialuminate (CaO.2Al2O3, calcium dialuminate), have interesting
hydration reactions that vary with temperature from 0 to 100 °C [41]. Fortunately,
the body maintains a constant temperature for the hydration reactions, which are
expressed in Eqs. 11.6 and 11.7 for the calcium aluminate (CaO.Al2O3) and calcium
dialuminate (CaO.2Al2O3) cement phases.

3 [ CaO.Al2 O3 ] + 12H 2 O → 3 ( CaO )·Al2 O3 ·6 ( H 2 O ) + 2 [ Al2 O3 .3H 2 O ] (11.6)

160 C. Primus

Calcium aluminate + water → amorphous calcium aluminate hydrate + aluminum

hydroxide.

3 CaO ( Al2 O3 )2  + 21H 2 O → 3 ( CaO )·Al2 O3 ·6 ( H 2 O ) + 5 [ Al2 O3 .3H 2 O ] (11.7)

Calcium dialuminate hydration + water → amorphous calcium aluminate hydrate +

aluminum hydroxide.
Calcium aluminate cements, like the calcium silicate cement phases, create a
high pH environment and release calcium ions, which are the prerequisites for
biomineralization (bioactivity/apatite formation). Some investigators have com-
bined these calcium aluminate phases with calcium silicate compounds to combine
the benefits of the silicate ion release for osteogenesis and the acid resistance of
calcium aluminate cement for dentistry.
Pozzolanic cement, Roman cement, is based on the reaction of silica with cal-
cium hydroxide or calcia (CaO). With water, the ceramics react as in Eq. 11.8,
where the proportions of the hydrated calcium silicate are indefinite (m, x, and n)
and depend on the composition. The silica and calcium hydroxide react with water,
forming a hard hydrated calcium silicate phase cement that differs from the tri-/
dicalcium silicates.

SiO 2 + Ca ( OH )2 + mH 2 O → ( CaO )x SiO 2 .nH 2 O (11.8)

[silica + calcium hydroxide + water → hydrated calcium silicate].
For construction, calcium silicate cement (Portland cement) supplanted pozzola-
nic cement in the 1800s, because Roman cement doesn’t have the strength of the
calcium silicate cements. Two dental products have been advertised as “fast-setting,
mineral trioxide aggregate–derived pozzolan cements,” but the components are not
known; they may include fine, amorphous silica and calcium hydroxide. The poz-
zolanic hydration reaction may cause shrinkage [42], an undesirable effect for den-
tal cements. No clinical or physical benefits have been published for the pozzolanic
dental cements [43].
The calcium aluminate, calcium silicate, and pozzolanic cements react with
water by surface hydration of the powder particles, which release calcium and
hydroxide ions into the tissue fluids. These ions enable the formation of HA on the
cement surface in vivo, which is herein denoted as bioactivity.

11.6 Pediatric Bioactive Ceramic Dental Cements

Many bioactive cement products are available for pediatric use, and some are listed
in Table 11.1. Various salient properties should be considered for choosing a bioac-
tive cement product including the ones discussed below: indications, composition,
format, packaging, and product characteristics.
 11

Table 11.1 Bioactive ceramic cement dental products

CaSO4,
Product name Manufacturer or Unit/ Radiopaque % Cement in Ca(OH)2, or
(alphabetical order) distributor Format multi-­dose? component powder CaCO3 SiO2 Other
Original MTA Courtesy of Dr. Powder/water Multi Bi2O3 70 3.7 1.7 2.2
M. Torabinejad
BC Root Repair Innovative Single paste Multi ZrO2, Ta2O5 63 3.2
Putty Bioceramix,
BC Fast-Set Putty distributed by Single paste Multi ZrO2, Ta2O5 55 7.7
BC Root Repair-jar Brasseler, FKG Single paste Multi ZrO2, Ta2O5 59 8.0
Dentaire, and
EdgeEndo
BioAggregate Innovative Powder/water Unit Ta2O5 88 5.4
Bioceramix
Biodentine Septodont Powder/liquid Unit ZrO2 83 13.7
Bio-C Repair Angelus Single paste Multi 37
Bioactive Ceramics for Pediatric Dentistry

ZrO2
BIOfactor MTA Imicryl Powder/liquid Multi Yb2O3 Unknown
BioMTA Diadent Powder/liquid Unit ZrO2, Yb2O3, 40 9.1
CaTiO3
BIO MTA+ Cerkamed Powder/liquid Multi ZrO2 Unknown
CEM Bionique Powder/water Multi BaSO4, ZrO2, 83 4.3
ZnO
Channels MTA Angelus/Schein Powder/liquid Multi Bi2O3 Unknown
CPM Endo Egeo Powder/liquid Multi Bi2O3, BaSO4 78 14.8
e-MTA Kids-e-dental Powder/water Multi Undisclosed Unknown
and gel
EndoBinder Binderware Powder/liquid Multi CaZrO3, ZrO2 80
EndoCem MTA Maruchi Powder Unit Bi2O3 36 42.0
EndoCem Zr Maruchi Powder/water Unit ZrO2 36 45.4 2 1.1
(continued)
161
Table 11.1 (continued)
162

CaSO4,
Product name Manufacturer or Unit/ Radiopaque % Cement in Ca(OH)2, or
(alphabetical order) distributor Format multi-­dose? component powder CaCO3 SiO2 Other
Endo-PASS DEI Italia Powder/water Unit BaSO4 73
Harvard MTA Harvard Dual-­ Unit Bi2O3 Unknown
compartment
capsules
Master-Dent MTA Dentonics Powder/gel Multi Bi2O3 77 1.8
Medcem Medcem Powder Unit None, or ZrO2 70 6.7
MM-MTA MicroMega Dual-­ Unit Bi2O3 Unknown
compartment
capsules
MTA Caps Acteon Dual-­ Unit CaWO4 48 18.3 0.4
compartment
capsules
MTAFlow Ultradent Powder/gel Multi Bi2O3 73 2.0
MTAFlow (White) Ultradent Powder/gel Multi Ta2O5 72 2.2
MTA gray or white Angelus Powder/liquid Multi Bi2O3 or 83 5.6 6.7
CaWO4
MTA HP Angelus Powder/liquid Unit CaWO4 81
MTA Plus Prevest Denpro Powder/gel Multi Bi2O3 77 1.8 1.7
MTA+ Cerkamed Powder/water Multi Bi2O3, ZrO2 67 2.0 14
MTA White Angelus Powder/water Multi CaWO4 92
NeoLINER LCa NuSmile Single-paste Multi Undisclosed Unknown
resin
NeoMTA 2 NuSmile, Avalon Powder/gel Multi Ta2O5 63 0.6 1.2
Biomed
NeoMTA Plus NuSmile Powder/gel Multi Ta2O5 72 1.3 1.6
NeoPUTTY NuSmile, Avalon Single paste Multi Ta2O5 47 1.0
Biomed
C. Primus
 CaSO4,
Product name Manufacturer or Unit/ Radiopaque % Cement in Ca(OH)2, or
(alphabetical order) distributor Format multi-­dose? component powder CaCO3 SiO2 Other
11

OliMTA Olident Dual-­ Unit Bi2O3 Unknown

compartment
capsules
Orbis MTA Orbis Dual-­ Unit Bi2O3 Unknown
compartment
capsules
Ortho MTA bioMTA Powder/water Unit Bi2O3 Unknown
PD MTA Produit Dentaire Powder/water Unit Bi2O3, BaSO4 50 36.4 4.7
Oxford MTA Oxford scientific Powder/liquid Multi or unit Undisclosed Unknown
or dual-­
compartment
capsules
ProRoot MTA Dentsply Sirona Powder/water Unit Bi2O3 76 3.6
(gray)
ProRoot MTA Dentsply Sirona Powder/water Unit Bi2O3 80
(white)
Bioactive Ceramics for Pediatric Dentistry

ReMTA Dental Solutions Powder/water; Unit and Bi2O3 Unknown

Israel single paste, multi-­dose
and dual paste
RetroMTA bioMTA Powder/water Unit ZrO2, CaZrO3 66
Smart MTA Sprig Powder/water Unit ZrO2 73
TheraCal LCa Bisco Single-paste Multi BaZrO3 78 5.5
resin
TheraCal PTa Bisco Dual-paste Multi BaZrO3, YbF3 20 33.8
resin
Trioxident Vladmiva Powder/water Unit ZrO2 79
Vivid Root MTA Pearson dental Dual- Unit Undisclosed Unknown
compartment
capsules
Well-Root PT Vericom Single paste Multi ZrO2 57 1.9
a
Resin-based
Blanks indicate the compound is not present
163
164 C. Primus

11.6.1 Indications

All the products in Table 11.1 are suitable for pulpotomies and other vital pulp pro-
cedures except the resin-containing cements: TheraCal® LC is only indicated for
pulp capping, NeoLINER™ LC is indicated for lining a cavity preparation (not pulp
capping), and TheraCal PT is limited to pulpotomies. EndoCem Zr is not indicated
for use as a base. Biodentine is the only material that is used as a temporary restor-
ative for up to 6 months. No product is specifically indicated for revascularization.
The resin-based materials contain monomers with dispersed bioactive cement
powders; however, they have not been as clinically successful as bioactive cements
without resin [44, 45], although they are reasonably priced. Resin-containing prod-
ucts are more suitable for indirect pulp capping [46]. TheraCal PT may be more
biocompatible than TheraCal LC, but not as biocompatible as MTA Angelus [47], a
non-resin containing bioactive cement. The clinical performance of TheraCal PT in
clinical tests of pulpotomies has not been tested, although a trial is underway
(NCT04167943).
No clinical superiority has been established for any other of the bioactive ceramic
cement products. The amounts of the cement vary in the products, as discussed
below, but a lower limit for cement content has not been established. Nor has an
“optimum cement composition” been determined, based on the individual cement
phases discussed above. In fact, commercial, construction-grade, Portland cement
has been considered as clinically effective as the dental bioactive bioceramic,
despite the construction-grade cement being coarse radiolucent, tending to wash out
and setting slower. However, using non-dental cement is ill-advised at best. Other
than bismuth oxide (discussed below), no superiority has been established for any
radiopaque additive, nor for any minor additive.

11.6.2 Composition

The composition of the bioactive ceramic products has been confusing for dentists
because of the various advertising claims and non-sensical, non-chemical product
names that are used, as mentioned previously. Furthermore, the cement compounds
were misidentified in the first publication of MTA’s [37] composition. Clinicians
can identify some components of the bioactive ceramic products by examining the
Safety Data Sheets (SDS) for a product, and reading the dental literature. The SDSs
should reveal any hazardous components but are often non-specific and incomplete
as to the composition.
Dental publications about the composition of these bioactive ceramic cement
products have often been based on scanning electron microscopy (SEM), including
atomic analysis using energy-dispersive spectroscopy (EDS), a.k.a. energy-­
dispersive X-ray spectroscopy (EDX or XEDS) [48]. The SEM/EDS technique can
image the product, before or after setting, and can identify the major atoms present.
For instance, calcium and silicon can be identified by SEM/EDS, but whether the
phases were dicalcium silicate or tricalcium silicate must be inferred because SEM/
11 Bioactive Ceramics for Pediatric Dentistry 165

EDS equipment cannot identify the ceramic phases (compounds). Another problem
with the EDS technique is that the spectra represent a sample deeper and wider than
the electron beam, which makes EDX quantitative analysis imprecise, particularly
if a material is being examined inside a tooth. Porosity also interferes with EDS
spectra; therefore, the spectra may not represent the composition where the electron
beam is “pinpointed.” Energy dispersive spectra is a “rougher” material science tool
for chemical analysis compared to other methods, such as wavelength dispersive
X-ray spectroscopy (WDS), performed with an electron microprobe, but less com-
monly used by researchers. X-ray fluorescence (XRF) is also used to analyze the
elements present in materials and can measure trace elements present in parts per
million, a much more precise elemental analysis than EDS. XRF atomic results are
converted to oxides using software, but XRF requires the destructive analysis of a
larger, non-­microscopic sample and does not reveal the compounds present. X-ray
diffraction is used by materials scientists to determine the crystalline phases (com-
pounds), such as the cement phases discussed before. X-ray diffraction may be per-
formed with powders or pastes, but does not identify trace metals, organic
compounds, amorphous materials, or crystalline phases present at less than about
1%. No one analysis technique is a comprehensive tool, but a combination of analy-
ses is useful for understanding materials and their behavior for its presentation in
the dental literature.
X-ray diffraction was used by this author to compare the bioactive bioceramics
powder, paste, and resin products suitable for pediatric dentistry. The results in
Table 11.1 also include some data from the dental literature, the gray literature, and
the companies’ safety data sheet (SDS) for products that were not available for
analysis. The total amount of the cement phases varied from 36 to 92% by weight,
and the cement phases were mostly tricalcium silicate and dicalcium silicate. Most
products contained more tri- than dicalcium silicate; however, EndoCem MTA and
EndoCem Zr contained only dicalcium silicate. Aluminate cement phases were
identified in Angelus MTA HP, CPM Endo, EndoBinder, BioMTA, MTA +, MTA
Caps, NeoPUTTY, PD MTA, ProRoot MTA, Sprig SmartMTA, RetroMTA,
TheraCal PT, and Trioxident. Two products contained the calcium aluminate cement
phases (CaO.Al2O3 or CaO.2Al2O3): NeoPUTTY and EndoBinder.
Some products contained significant amounts of calcium oxide, hydroxide, or
calcium carbonate. The calcium compounds are not cement phases and do not add
radiopacity. Calcium sulfate was present in some products, perhaps for setting con-
trol or calcium release. Other minor components were identified by XRD: magne-
sia, silica, calcium hypophosphite, and calcium chloride. Amorphous or
low-crystallinity components may be present in the powders or pastes including
fumed silica, chitosan, cellulose, and various clays; these compounds cannot be
discerned by X-ray diffraction, as they would only appear as broad humps, not sharp
peaks in the X-ray diffraction spectra. However, these additives have been men-
tioned in patents for such materials, used to thicken and stabilize pastes for better
handling. These non-cement components may be included to augment calcium ion
release, speed up setting, increase strength, or reduce the firing temperature required
for manufacturing the cement (e.g., MgO).
166 C. Primus

11.6.3 Radiopacity

Diverse ceramic powders have been blended into the bioactive ceramic cements for
radiopacity (Table 11.1), which are, in order of increasing molecular weight, zinc
oxide (81 g/mol), zirconia (123 g/mol), calcium zirconate (179 g/mol), ytterbium
fluoride (230 g/mol), barium sulfate (233 g/mol), barium zirconate (277 g/mol),
calcium tungstate (288 g/mol), ytterbium oxide (394 g/mol), tantalum oxide (442 g/
mol), and bismuth oxide (465 g/mol). Newer bioactive cement tend to contain more
radiopaque powder than the 20 weight percent bismuth oxide in the ProRoot MTA
patent. The radiopacities of the bioactive ceramic cements vary from about 1 to
8 mm of equivalent aluminum for pediatric bioactive cements, when tested per the
standard method of ISO 13116. For reference, dentin has a radiopacity equivalent to
about 1 mm of aluminum. Resin-containing products, such as TheraCal LC and PT,
have the lowest radiopacity (~1 mm equivalent Al) [49].
Antibiotics or injury may discolor teeth, but the gray and white ProRoot MTA
products also discolored teeth. Discoloration can be immediate from using a gray-­
colored powder such as the original, dark gray, ProRoot MTA, containing the ferrite
cement phase. Surprisingly, the white ProRoot MTA also caused gradual, delayed
discoloration, especially in the thinner, primary teeth [50]. The primary cause of
discoloration has been traced to the inclusion of the bismuth oxide powder used for
radiopacity. When exposed to light and certain chemicals, Bismuth oxide forms
darker-colored bismuth compounds, such as bismuth subcarbonate, Bi2O2(CO3),
sodium bismuthate, or reddish Bi2O4-x [51], when exposed to light and certain chemi-
cals. The color change is caused by bismuth ions that transform under oxidation or
exposure to light from trivalent (Bi+3) to pentavalent (Bi+5). The darkening of the
bismuth oxide in the bioactive cements was not esthetic, but does not compromise
the dental cements’ safety or efficacy [50]. Although the original ProRoot MTA
products continue to contain bismuth oxide, most newer products do not contain this
radiopaque component. Notably, many products in Table 11.1 have “MTA” in their
trade name, but do not contain bismuth oxide. Therefore, not all “MTA” products
discolor, despite some generalizations made in the literature. The only common char-
acteristic of the so-called MTA products is the presence of calcium silicate cement.

11.6.4 Pastes and Resins

Another tool of materials scientists is thermogravimetric analysis (TGA). Using this

technique, a small sample is gradually heated to about 1000 °C, while its weight
change is monitored. TGA was used to measure the amount of organic liquid or
resin present in some of the single- and dual-paste products (Table 11.2). About 15
to 30% organic liquid, such as glycols of various molecular weights, are used in
some cement pastes that set in vivo. The EndoCem paste is known to contain another
liquid, dimethyl sulfoxide (DMSO). For all these paste products, the organic liquid
diffuses from the cement paste in vivo, while water from tissue fluids migrates into
the cement pastes to cause setting. Resin-containing pastes are different because
11 Bioactive Ceramics for Pediatric Dentistry 167

Table 11.2 Bioactive ceramic cement dental paste products for pediatric dentistry
Product name % Organic
(alphabetical order) Manufacturer or distributor Format liquid % Resin
BC Root Repair Innovative Bioceramix, distributed Single 16
Putty by Brasseler, FKG Dentaire, and paste
BC Fast-Set Putty EdgeEndo Single 15
paste
BC Root Repair-jar Single 19
paste
Bio-C Repair Angelus Single
paste
NeoLINER LCa NuSmile Resin Unknown
NeoPUTTY NuSmile, Avalon Biomed Single 20
paste
TheraCal LCa Bisco Resin 33
TheraCal PTa Bisco Dual-­ 37
paste
resin
Well-Root PT Vericom Single 21
paste
Resin-based
a

resins remain in place after setting. Polymerized resins control the release of the
cement ions that are embedded in the resins. As a result, bioactivity (ion release) is
lower in these resin products. Resin products contain about 35% monomer.

11.6.5 Format

The formats of the bioactive ceramic cement products vary widely, with some more
convenient and others more affordable [27]. The products contain bioactive cement
powder formatted as (1) powder and liquid that the clinician mixes into a viscous
paste, (2) single pastes, or (3) resin-based materials (that contain some bioactive
cement particles). Powder/liquids products set because the water in the liquid starts
the setting; these products may be single or multi-dose in format. Pastes set because
tissue fluids provide water for setting. Well-Root PT is a single-dose, single paste in
a compule-type dispenser, but usually pastes are sold in multi-dose syringes. Resin
materials set because the matrix is cured, but the cement is not set except on the
surface where it is exposed to tissue fluids. The formats of these bioactive ceramic
cement products are important to clinicians for convenience, speed of treatment,
and cost. Table 11.1 lists many bioactive ceramic cement products for pediatric
dentistry, designating the format as single or multi-dose.
The first bioactive bioceramic cement kit, ProRoot MTA, contained foil sachets
of powder and ampoules of water for clinicians to mix as individual doses. The
sachets contain 0.5 g, much more than needed for a pediatric dose (<0.1 g), and
resealing the sachets is not possible. This foil sachet format has been copied for
products such as RetroMTA, PD MTA, Trioxident, and reMTA (Fig. 11.6a) and the
original BioAggregate product.
168 C. Primus

Unique capsules of powder have been offered as unit doses by Septodont,

Medcem, and Angelus, companies containing 0.7, 0.35, and 0.19 g (Fig. 11.6b).
Biodentine (Septodont) and Angelus capsules are plastic, whereas Medcem MTA
and Endo-PASS MTA are sold in gelatin capsules. Septodont Biodentine® and
Angelus MTA HP kits include ampoules of water-based liquid containing a salt and
polymer (calcium chloride and an unidentified carboxylate polymer) to impart
faster setting and higher strength [52]. The dentist adds the Biodentine liquid drop-
wise to the powder in the capsule; then the capsule must be triturated to mix. 0.7 g
of powder per capsule of Biodentine is large for one tooth but useful when many

Fig. 11.6 (a) Unit-dose packaging of bioactive ceramic cement powders in foil sachets. (b) Unit-­
dose packaging of bioactive ceramic cements in capsule or vials, used for powder or liquid or both.
Some products include foil pouches; others use plastic packages. The centrifuge for mixing
OrthoMTA is shown in the lower right-hand corner. (c) Dual-compartment capsule products for
powder and liquid. (d) Multi-dose kits of bioactive ceramic powder and liquid. (e) Paste forms of
bioactive cements that self-set. (f) Resin-based materials that set by light curing or dual curing
11 Bioactive Ceramics for Pediatric Dentistry 169

Fig. 11.6 (continued)

170 C. Primus

Biodentine XP

Fig. 11.6 (continued)

11 Bioactive Ceramics for Pediatric Dentistry 171

Fig. 11.6 (continued)

172 C. Primus

Fig. 11.6 (continued)

11 Bioactive Ceramics for Pediatric Dentistry 173

Fig. 11.6 (continued)

174 C. Primus

teeth need treatment, such as pediatric pulpotomies [27], or as a temporary restor-

ative. MTA HP powder and liquid are hand-mixed on a glass or impermeable pad.
The Medcem MTA and Endo-PASS MTA gelatin capsules tend to be brittle and
messy when opened; they must be mixed with a clinician-supplied liquid. Other
unit-dose packaging options for the bioactive cement powders have included plastic
“centrifuge” vials, often with a 0.3 g dose as shown in Fig. 11.6b. For the OrthoMTA
product, the dentist mixes with water in the vial and then uses a battery-operated
centrifuge for mixing. These unit-dose powder and liquid capsules and vials are
often, but not exclusively, sold in protective foil pouches to prevent the ingress of
water. Some of the vials of water-based liquid are also packaged in foil pouches,
some resealable, others not.
Dual-compartment capsules for trituration of a unit-dose are shown in Fig. 11.6c.
These capsules are similar to amalgam or glass-ionomer unit-dose capsules and
usually provided in foil pouches. The capsules have two compartments: one for the
cement powder and one for water or a water-based liquid separated by a membrane
of foil. The capsules are “activated” by the dentists compressing a plunger and then
triturating the capsule. The wet cement mixture is dispensed by opening the capsule
or using a capsule product that has a dispensing tip. Dual-compartment capsules for
trituration usually contain 0.3 g of powder and water and have been sold by Acteon,
Harvard, Micro-Mega, Orbis, Oxford, and Pearson. Usually, two capsules are pack-
aged in a foil pouch. From the similarity of the capsule products, one may surmise
that some are private labeled. In 2022, Biodentine introduced their unique design of
a single-dose, dual-compartment capsule and a special mixer. The cost of dual-
compartment capsules is higher per dose or per gram, compared to hand-mixed and
multi-dose products.
Multi-dose powder/liquid kits of bioactive cements (Fig. 11.6d) began with the
first Angelus MTA products, gray and white, which included a bottle of cement and
a dropper bottle of water. The advantage of multi-dose bottles is the clinical control,
i.e., one has to dispense only what is needed. Mixing a powder and liquid requires a
bit of skill and familiarity but allows a clinician to customize the viscosity and han-
dling. Variations in the powder-to-liquid ratio have been explored; a weight ratio of
3 to 1 is most common and often used in research tests, but ratios have been evalu-
ated from 2:1 to 4:1 [53]. Higher powder-to-liquid ratios increase the viscosity of
the mixed cement, shorten the setting time, and lead to a higher strength cement.
Hand, ultrasonic, and trituration mixing have been evaluated for their effects on
mixed MTA Angelus, but only small differences were observed. The relatively high
cost of the calcium silicate cement products has made mixing an issue, because of
the potential for waste of mixed, unused cement paste, but savvy assistants can
avoid waste with a little practice. Water-based gel is included in some of the multi-­
dose kits shown in Fig. 11.6d for products including MTA Plus®, NeoMTA Plus®,
NeoMTA®2, Masterdent® MTA, MTAFlow® (white and gray), and e-MTA products.
Water-based gels are higher in viscosity (thicker) than water, from which one sur-
mises the gels contain water-soluble polymers or organic liquids. The gels improve
the handling, ease of placement, and washout resistance of the mixed cements [54].
Some multi-dose products include water (CEM) or a salt solution (BioMTA +).
11 Bioactive Ceramics for Pediatric Dentistry 175

Paste products (Fig. 11.6e) that set in vivo are the latest format of the bioactive
ceramic cements. Such single-paste products may be denoted as premixed pastes or
putty and have a high viscosity that is a thick, putty-like, consistency similar to
IRM® and quite suitable for pediatric dental procedures. These pastes are available
either in syringes or a small “pot.” The syringes have had superior shelf life com-
pared to one, expensive brand sold in a small jar [55]. Only Well-Root PT paste is
sold in compules for individual doses. For these pastes, the cement powder has been
blended into a water-free, organic liquid. Being water-free, the cement doesn’t set
in the syringe or compule. However, when the paste is placed in vivo, water from the
body tissues diffuses into the paste and causes setting of the cement, while the
organic liquid diffuses into the body tissues; no light activation and no catalyst are
needed. These pastes are very washout resistant and provide a very fast convenient
dispensing option. These putty-like pastes set over a few hours because the body has
to supply the water for setting. These paste products of bioactive cements are con-
venient and economical for dispensing, with little waste; however, the pastes cost
more per gram than the powder-liquid systems.

11.6.6 Packaging Materials

Clinicians should be aware that all packaging materials are imperfect barriers and
usually control the shelf life of products. Water can permeate all barriers to powder
packaging, including foil and plastics, although multi-layered foil/polymer reseal-
able pouches are superior. Even glass bottles may allow water to enter through the
plastic cap and its seal. Some of these bioactive cement powders are packaged in
foil sachets (small pouches) for powder; other products package the cement powder
in glass or plastic bottles, capsules, or vials as noted before. Desiccants in the bottles
of powder are used for NeoMTA2 powder, MTAFlow, and the MasterDent products
to prolong the powders’ shelf life. When water permeates the bioactive ceramic
cement powder packaging, the setting time is lengthened; handling is degraded by
partial hydration, making it granular (crumbly); and the set cement is weaker. This
problem is worse for the foil sachets which cannot be resealed, such as the one used
for ProRoot MTA.
Evaporation from the unit-dose containers of water-based liquid is also impor-
tant. Over the shelf life of the product, usually 2 to 3 years, evaporation of water will
occur from the unit-dose liquid containers, which increases the powder-to-liquid
ratio of unit-dose products. Also, it is difficult to precisely package weights of pow-
der in vials, ampoules, or pouches. Liquid dose packaging can be more accurate
than powders, but the evaporation through the packaging can reduce the amount of
liquid over time. These minor variations can be detectable to clinicians. Slightly
thicker mixtures may be detected when mixing unit-doses of powder and liquid that
are nearing their expiration date. Also, select dental materials are sold as sterile,
which must be marked as sterile. Most dental restoratives or cements are not sterile.
Some authors have believed that the bioactive cement products are sterile or have
sterile liquid components; however, sterile products are always marked as sterile.
176 C. Primus

Combining all these factors, these bioactive ceramic cement products have a
shelf life of 2–3 years, as do most dental products.

11.7 Cement Product Characteristics

The first calcium silicate cement products (ProRoot MTA and MTA Angelus) were
clinically effective, but tended to wash out, had a long setting time (>2 h), caused
tooth darkening, and had high cost (~$50/g). The products were maligned as “just
expensive Portland cement.” Newer and modified products have moderated these
issues. The current hydraulic, bioactive ceramic cements have easier handling and
faster setting time, do not darken teeth, and have lower cost while maintaining
excellent clinical performance. These product improvements have been made pos-
sible by manufacturers making finer particles sizes of powders, modifying the liq-
uids for mixing, adding some other ceramic powders, inventing paste forms, and
incorporation of non-bismuth oxide radiopaque ceramic powders, all amid interna-
tional competition. The current properties of various bioactive cements for pediatric
dentistry are discussed below.

11.7.1 Handling

The original MTA prototype and ProRoot MTA was considered “sandy” in consis-
tency, that is, the powder was coarser than powder products to which dentists are
accustomed. Manufacturers have improved the powders, making them very fine,
eliminating the coarse powders. Newer, more radiopaque powders are also very
fine, with some powder particles in the nanoparticle range (<0.1 μm, <100 nm).
Finer particles contribute to easier handling, better cohesion when mixed with liq-
uids, and faster setting/hydration. The newer, water-based solutions and water-based
gels create benefits of washout resistance, easy handling and placement, a more
desirable “plastic” consistency, and faster setting of the bioactive cements. Many of
the bioactive bioceramic cements can be mixed to a dough-like consistency that can
be picked up with a small instrument like amalgam carriers, or the small “MTA”
carriers. (See Fig. 11.7.) These improvements eliminate the need for special “MTA”
instruments for clinical placement. The paste products streamline the application
with no need for mixing; however, the viscosity is not usually adjustable, unless
extra liquid or powder is supplied.
Practice is often needed to economically mix the bioactive, powder-liquid, multi-­
dose, cement products. Impermeable pads are a necessity; otherwise, the pad
absorbs the liquid and creates problems; glass palettes are especially suitable. A
medium-stiffness metal spatula is best to ensure the powder and liquid are well
mixed; plastic spatulas are not well designed for mixing these very fine powders.
Problems with mixing proportions can arise because scoops and drops vary among
users. When too much powder is added to the liquid, the mixture is dry and crum-
bly; however, more liquid should be added in small increments, usually less than a
11 Bioactive Ceramics for Pediatric Dentistry 177

0.8mm 1.2mm

1mm
1.8mm

0.80mm 0.99mm 1.60mm

Fig. 11.7 Instruments for mixing and placing bioactive bioceramics having a putty-like
consistency

drop. When too much liquid is added to the powder, the mixture is unmanageable,
thin, and slow to set. When the mixture is thin, the tendency is to add more powder.
If time permits, the thin mixtures can be spread out to allow the water-based liquid
to evaporate and thicken the cement. Very little bioactive cement is needed clini-
cally, so any increment of powder added to a thin paste should be very small, less
than the scoop provided by a manufacturer. Adding powder can create a lump of
cement that is much more than needed – a costly mistake!

11.7.2 Setting Time

Dentists thrive on fast-setting products, but the original ProRoot MTA powders
mixed with water required more than 2 h to set [37]. Newer bioactive ceramic
cement products have shorter initial setting times, often about 15 min [56]. The final
(effective) setting time for the non-resin products is longer, usually several hours.
Various means have been used to reduce the setting time, including the use of finer
particles and the inclusion of calcium chloride, reduced calcium sulfate content, and
178 C. Primus

water-soluble polymers in water-based solutions for mixing with powders. Higher

temperature and humidity and smaller and thinner samples speed the setting of the
bioactive ceramic cements.
Setting time for these cements has been measured with the Gilmore indentation
apparatus. The Gilmore apparatus has two indenters: one indenter has a larger diam-
eter and a lighter weight to judge the initial set time, and the other indenter is
heavier, which has a smaller diameter indenter for the “effective” (final) set. Unset
materials allow an indentation on the sample surface. Notably, the current initial and
effective (final) setting times for the bioactive ceramic cements are longer than
required for base or liner materials (less than 10 min) in ISO 9917-1 or ISO 3107
standards for water-setting cements and zinc-oxide eugenol materials.
A few bioactive ceramic cement products have compensated for longer setting
times than “conventional” dental materials by being washout resistant. Completion
of setting of the bioactive cement is not required for many indications, such as pulp-
otomies and crown placement. Some bioactive cement products easily remain
within the pulp chamber; while a crown is seated, setting is completed after the
procedure. Products with gels for mixing with the powder and the single cement
pastes create excellent washout resistance. Bioactive cement powders that are mixed
with plain water or anesthetic solution are not washout resistant. When a crown
preparation is required after the pulpotomy, a thin layer of glass ionomer cement,
compomer, resin-modified glass ionomer, or flowable composite can be used to sta-
bilize the bioactive ceramics in the pulp chamber; these restorative materials enable
easier rinsing after crown preparation is complete and stabilize the bioactive cement.
Despite the perceived goal for fast-curing, the newer, washout-resistant products,
including the slower-setting single pastes, are popular and convenient.
The products discussed above all rely on the hydration of the cement to set.
Dentists are very familiar with fast-setting, light-curing, single-paste composites for
restoratives, which start to set when exposed to blue light. Dual-paste products are
also common in dentistry, where the components are mixed to start the setting reac-
tion. Some two-component, resin-based materials are dual-cured, that is, light and
chemical curing occurs. Resin-based products containing bioactive cements avail-
able from BISCO or NuSmile contain the calcium silicate cements but rely on the
setting of their polymer (resin) matrix (Fig. 11.6e). TheraCal LC paste contains a
light-curable resin as does NeoLiner LC. TheraCal PT is a two-paste, dual-cured,
resin product for pulpotomies. Resin-based materials are also washout resistant, but
not as clinically effective as non-resin-based cements because the resin matrix con-
trols the release of ions from the bioactive powder.

11.7.3 Solubility

Bioactive calcium silicate/aluminate cements are classified as a permanently

implanted material according to ISO 7405, a standard for biocompatibility of dental
materials this is an indication where the material should be insoluble and, usually,
non-porous. Researchers have reported some cement products have less than 10%
11 Bioactive Ceramics for Pediatric Dentistry 179

porosity, with one-half being closed pores, and solubility less than 3% after 72 h
[57]. Others have reported high solubility (~20%), water sorption (~12%), and
porosity (40%) for other products [58]. These solubility measurements are a point
of confusion because high porosity or solubility would allow bacterial migration
and dissolution, which is contrary to the excellent clinical performance of bioactive
ceramic cement materials.
Calcium silicate and calcium aluminate bioactive cements inherently release cal-
cium and hydroxide ions into the tissue and create a high pH (>10) environment,
which continue to be released over 4 weeks in diminishing amounts. The chief ben-
efit of the persistent alkalinity has been the formation of the biomineralization layer
on the surface, but it also contributes to local antibacterial [59] and antifungal effects
[60]. The solubility test method of the ISO 6876 standard tests requires that samples
with a high surface-to-volume ratio be soaked in water then the material eluted into
the solution is measured. This method emphasizes the weight loss from the dissolu-
tion of calcium hydroxide from the surface, but calcium hydroxide is essential for
bioactive bioceramics. The test method currently does not measure the insolubility
of the cement matrix. The test method is inappropriate for these cement materials
and doesn’t illustrate the stability of the calcium silicate and calcium aluminate
cements. As a practical point, if calcium silicate cements were soluble, concrete
structures would dissolve and collapse!

11.7.4 Dimensional Stability

Dental materials may shrink or expand during setting. Shrinkage can allow bacterial
infiltration (microleakage), and expansion can cause tooth fracture. Microleakage
avoidance is important in preventing bacteria in the oral cavity from migrating into
the tooth or reaching the alveolar bone. Many test techniques have been used to
assess leakage: dye penetration, dye sorption, bacterial or endotoxin infiltration, and
fluid filtration. The lower microleakage of the bioactive ceramic cement products is
well established, particularly compared to amalgam or zinc oxide-eugenol cement.
Lower microleakage may be attributed to the dimensional stability [61, 62] of the
bioactive ceramic cements. Linear changes as small as 0.5 to 1.0% [61] after 30 days
have been measured, with some dependence on the powder-to-water ratio used for
mixing. Volumetric changes have also been reported from computerized micro-­
tomography (μCT) tests; however, the results are less than ±1% [63]. This dimen-
sional stability is another advantage of using these calcium cements.

11.7.5 Bonding

Bonding is essential for restorative materials, and shear bond strengths to tooth
structure are expected to be high. The bioactive ceramic cements are placed under
restorative materials, and they function to stop bacterial migration and induce pulpal
or periapical tissue healing; they are not used for their adhesive qualities. Pushout
180 C. Primus

strength tests have been used to test calcium silicate materials’ bonding to teeth.
Such tests have also served as a surrogate for assessing microleakage, shear bond
strength, and dentinal tubule penetration. The pushout bond-strength values vary
widely, and the techniques have been criticized [64] for the experimental designs.
Generally, any bonding values have been low compared to restorative materials.
Etching is a common procedural step for bonding in dentistry, but etching is of
no benefit in placing restoratives over bioactive cements. Acids will soften, not
roughen, the hydrated matrix of the calcium cements; neither chemical nor mechan-
ical adhesion occurs via etching the bioactive ceramic cements. Nor have polymer
adhesives over the calcium silicate/aluminate cements have improved bonding [65].
A high bond strength of these materials to restoratives or teeth is not essential, and
high bond strengths have not been measured. The likelihood of displacement or
“debonding” of the bioactive cements is very low because they are used intracoro-
nally. No case reports of dislodgement of the calcium silicate cements have been
published. Bonding restorative materials over the bioactive ceramic cement should
focus on bonding the restorative to the surrounding tooth structure, without expect-
ing any added benefit of bonding to the underlying bioactive cement.

11.7.6 Strength

Ceramic materials perform best in compression and are weak in tension. Luckily,
for pediatric dental indications, the bioactive cements undergo compressive forces
under a restorative material. Compressive strengths have varied widely for bioactive
cements. Some materials meet the ISO 9917-1 standard’s requirement (>50 MPa),
with the caveat of testing after a few days of setting, not after the 24-h time period
given in the test method [37]. However, in the ISO 3107 standard for zinc oxide
eugenol used as a base, the requirement is only 5 MPa; therefore, bioactive ceramic
cements can be used as a base, e.g., indirect pulp capping. An interesting aspect of
the calcium silicate cements is that strengthening (hydration) continues after set-
ting, for about 4 weeks [66], unlike other dental materials.

11.7.7 Costs

The cost of the original MTA products has been a sore point between manufacturers
and dentists [16]. Costs are now lower than the original materials [27], although still
significant on a per dose basis, compared to other dental materials. Competition
among manufacturers is expected (hopefully!) to continue to lower the price per
dose to levels competitive with other dental products. Today, multi-dose, powder-­
liquid systems are very economical per dose. The single-paste materials have mini-
mal waste and may be affordable if judiciously dispensed.
11 Bioactive Ceramics for Pediatric Dentistry 181

11.7.8 Other “Bioactive” Materials

The bioactive ceramic cements have prompted a trend in dentistry for companies to
advertise materials as “bioactive.” Some nominally “bioactive” materials release
ions, but do not create the surficial hydroxyapatite layer created by the calcium sili-
cate and calcium aluminate cements. Clinical benefits of bioactivity may be absent
or erroneously advertised in materials such as resin-modified glass ionomers that
release ions; sometimes, the SEM/EDS spectra in teeth have been misinterpreted.
Glass-ionomer cements are well known in dentistry for their fluoride ion release,
which does exchange at body temperature into the apatite of enamel or dentin, to
harden (remineralize) the tissue. However, fluoride ion release alone does not create
biomineralization/bioactivity, that is, formation of HA. “Giomer” glass releases six
ions that may be beneficial, but not form a HA layer: fluoride, sodium, strontium,
aluminum, silicate, and borate. The pH created by glass ionomer cements is less
than 7, which is unable to cause the biomineralization reaction of Eq. 11.1. The term
“biointeractive” is more appropriate for such products, rather than bioactive or
biomineralizing. No well-documented clinical and histological evidence bioactive
ability has been published for biointeractive materials, and some analyses are spuri-
ous using SEM/EDS analysis.

11.8 Summary

Bioactive calcium silicate and calcium aluminate ceramic cements are wonderful
materials for pediatric dentistry, general dentistry, and endodontics. Contemporary
calcium silicate or calcium aluminate cement products are known by many names;
chief among them is MTA, which is a trade name that indicates products containing
the calcium silicate cement powder. The key to these bioactive calcium cements’
performance is the bioactivity/biomineralization that occurs because of their high
pH and calcium ion release when the cements react with water. The ion release
continues over a few weeks, providing local antimicrobial effects. The products
containing the bioactive bioceramic cements form a layer of hydroxyapatite in con-
tact with tissue fluids. This layer assists with healing, unlike alternative treatments
such as formocresol or ferric sulfate.
Bioactive bioceramic products have been improved over the past 25 years since
their introduction. Newer products have finer powders and convenient liquids or
gels that make handling and placement easier with stability when placed (washout
resistance). Various additives have reduced the setting times of the powder/liquid
products although the cement products set more slowly than composite materials.
Powder-liquid products usually set in about 15 min, but do not delay a procedure;
completion of setting is not required before a restorative is placed. Novel pastes
have made the bioactive cements more convenient for pediatric dentists; they can be
the most cost-effective and convenient and set in vivo over a few hours.
182 C. Primus

Discoloration has been eliminated, even for some products with the trade name
“MTA,” by choosing products without bismuth oxide. These bioactive cements have
only limited ability to bond, but their high dimensional stability and insolubility is
suitable for preventing microleakage. Packaging innovations have included unit-­
dose and multi-dose products, for convenience and economy. Products with resins
for light-curing or dual-curing exist, but don’t have the same bioactivity or versatil-
ity as the powder/liquid or self-setting paste products.
Bioactive cements eliminate the need for formocresol and its potential health
risks. Furthermore, bioactive cements do not cause the internal resorption that has
characterized ferric sulfate-treated pulpotomies. No significant differences have
been confirmed among the non-resin products for histological performance; how-
ever, clinicians may choose a product based on convenience or cost. Resin-­
containing products remain confined to limited indications with fewer benefits than
the other products.
With the continuing clinical success of such products, pediatric dentists should
embrace these bioactive ceramic cements for their “everyday” dental procedures to
offer the highest level of care. Bioactive cement products will continue to evolve for
new indications, such as primary tooth pulpectomies, cervical resorption, and socket
grafts. When all their physical properties are considered, calcium silicate and cal-
cium aluminate cements are well suited as pediatric dental materials for procedures
contacting pulp and periapical tissues. The clinical results, discussed in other chap-
ters, confirm that the bioactive bioceramic cements are the new gold standard for
minimally invasive, conservative pediatric dentistry procedures.

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Primary and Permanent Teeth Treated
with Direct Pulp Capping 12
James A. Coll

Contents
12.1 Purpose 187
12.2 Goals 188
12.3 Definitions 188
12.4 Pulpal Diagnosis 189
12.5 Caries Removal Methods Affect Pulpal Treatment Methods 189
12.5.1 Complete Caries Removal 189
12.5.2 Stepwise Caries Removal (SW) 189
12.5.3 Selective (Partial) Caries Excavation 190
12.5.4 No Caries Removal 192
12.6 Vital Pulp Therapy for Carious Pulp Exposure Having Normal Pulp or Reversible
Pulpitis Diagnosis 193
12.6.1 Direct Pulp Capping Primary Teeth 193
12.6.2 Direct Pulp Capping Permanent Teeth 195
12.7 Vital Pulp Therapy for Carious Pulp Exposure Having Irreversible Pulpitis
Diagnosis 196
12.8 Considerations Before DPC in Primary and Permanent Teeth 197
12.9 Conclusions 198
References 199

12.1 Purpose

Direct pulp cap (for primary teeth occurring during caries removal) has been advo-
cated by the American Academy of Pediatric Dentistry (AAPD) since 2017 [1, 2].
DPC has been shown to be an effective treatment after carious exposures in perma-
nent teeth for a longer time [3, 4]. For permanent teeth, the American Association of
Endodontists (AAE), in 2013 and updated in 2019, advocated DPC only for

J. A. Coll (*)
University of Maryland Dental School, Baltimore, MD, USA

© The Author(s), under exclusive license to Springer Nature Switzerland AG 2023 187
A. B. Fuks et al. (eds.), Contemporary Endodontics for Children and
Adolescents, https://doi.org/10.1007/978-3-031-23980-9_12
188 J. A. Coll

mechanical exposures during caries excavation [5]. More recently, the AAE issued
a new position paper on vital pulp therapy (VPT) [6]. It stated calcium silicate-type
materials such as MTA should be used for VPT. For asymptomatic or symptomatic
permanent teeth with irreversible pulpitis, DPC success has been reported after 1
year as 94.7% [7] and after 2–3 years 84–86% in cariously exposed vital molars [8].

12.2 Goals

The goals of this chapter are to provide the reader with the most current evidence-­
based research on primary and permanent teeth DPC success.

12.3 Definitions

Bioceramics refers to any of the calcium silicate pulp materials for DPC or
pulpotomy.
MTA stands for mineral trioxide aggregate which is a mixture of calcium silicate
cements (primarily tricalcium and dicalcium silicate), bismuth oxide, and smaller
amounts of dicalcium silicate, tricalcium silicate, tetracalcium, aluminoferrite, and
calcium sulfate dihydrate known as gypsum.
Primary teeth DPC is indicated for carious pinpoint to 1 mm pulp exposures [2].
Permanent teeth DPC indicated for 0.25–2.5 mm pulp exposures resulting from
caries removal [9].
Primary tooth reversible pulpitis is the pulpal diagnosis for a tooth without
signs or symptoms of irreversible pulpitis that has provoked pain from eating for a
short duration (5–10 min) [10].
Primary tooth irreversible pulpitis and/or necrosis will exhibit any one of the
following: history of unprovoked toothache; sinus tract, soft tissue pathology, or
gingival swelling not associated with periodontal disease; abnormal mobility not
associated with exfoliation; radiographic furcation or periapical radiolucency;
external or internal radiographic root resorption [10].
Definitions by the AAE are as follows: [11]
Permanent tooth, reversible pulpitis is based on subjective and objective find-
ings indicating that the inflammation should resolve and the pulp return to normal.
Permanent tooth asymptomatic irreversible pulpitis is based on subjective and
objective findings indicating that the vital inflamed pulp is incapable of healing due
to inflammation produced by caries, caries excavation, or trauma but is asymptomatic.
Permanent tooth symptomatic irreversible pulpitis is based on subjective and
objective findings indicating that the vital inflamed pulp is incapable of healing and
has lingering thermal pain, spontaneous pain, or referred pain.
12 Primary and Permanent Teeth Treated with Direct Pulp Capping 189

12.4 Pulpal Diagnosis

For pulpal diagnosis in primary and permanent teeth, see Chap. 9. However, it is
known diagnostic tests are of limited value in primary teeth and in immature perma-
nent teeth [12]. There is insufficient EBD research to make a recommendation to
accurately diagnose the pulp’s vitality resulting from deep caries in primary teeth.
The best assessments are from symptoms, palpation, percussion, and tooth mobility.
For immature permanent teeth, the same assessments apply; for permanent teeth
with mature apexes, cold, heat, percussion, and electric pulp tests can aid the
diagnosis.

12.5 Caries Removal Methods Affect Pulpal

Treatment Methods

12.5.1 Complete Caries Removal

Complete caries removal has also been termed “non-selective” whereby all caries is
removed till hard dentin is reached [13]. This method involves removing all the
infected and affected carious dentin with burs, hand instruments, or chemical
methods.

12.5.1.1 Complete Caries Removal and Rate of Pulp Exposure

A pulp exposure can occur when complete excavation of deep caries is employed.
A meta-analysis showed for deep caries in primary and permanent teeth com-
plete caries excavation has three times the odds ratio of creating a pulp exposure
compared to selective or stepwise excavation [14]. Another systematic review [15]
showed partial caries removal reduced the incidence of an exposure by 77% com-
pared to complete excavation. In 2016 a meta-analysis showed almost half the den-
tists in practice still employ complete caries removal for deep caries in primary and
permanent teeth [16]. As a result of these studies and other reasons, complete caries
removal for deep caries is not recommended [17].

12.5.2 Stepwise Caries Removal (SW)

An alternative method of deep caries removal is stepwise caries removal. It is

accomplished over two patient visits. The first visit completely removes the decayed
dentin along the peripheral walls till hard dentin is reached. On the pulpal floor, car-
ies is removed till soft dentin is reached avoiding a pulp exposure [13]. A temporary
restoration such as a glass ionomer is placed covering the soft dentin on the pulpal
floor (Figs. 12.1 and 12.2). The theory is that SW will allow remineralization of the
190 J. A. Coll

Fig. 12.1 Preoperative

view of interproximal
caries in first primary
molar before stepwise
caries removal

Fig. 12.2 View of first

primary molar and
temporary filling after first
visit of stepwise caries
removal

affected dentin and form more tertiary dentin [18]. The carious lesion is reentered in
8–12 weeks and caries removal carried out leaving only central yellowish or grayish
hard dentin in the pulpal floor (Fig. 12.3). A final restoration is placed with the
intention to seal the pulp from any microleakage [19]. Systematic reviews and meta-
analyses have shown SW significantly reduced pulp exposures compared to com-
plete caries removal [14, 15].

12.5.3 Selective (Partial) Caries Excavation

The third type of caries excavation is termed “selective or partial caries removal.” It
is completed in one appointment where the dentist completely removes the periph-
eral decay but intentionally leaves the deepest leathery caries in place and covers it
with a well-sealed durable restoration [13]. Selective caries removal done in one
appointment with local anesthesia would be the recommended treatment for chil-
dren. This method is used for indirect pulp treatment and normally avoids a pulp
12 Primary and Permanent Teeth Treated with Direct Pulp Capping 191

Fig. 12.3 Second visit

stepwise excavation
showing central yellowish
hard dentin after second
caries removal visit

Fig. 12.4 Preoperative

view before selective caries
removal in a mandibular
permanent right first molar

exposure (Figs. 12.4 and 12.5). Selective caries removal omits the reentry and sec-
ond excavation done with SW and avoids having to administer anesthesia a second
time (Fig. 12.6). In addition, possible failure of a temporary filling done with SW is
avoided. Selective removal tries to shift the microbial balance in deep lesions to
allow dentin remineralization and arrest the carious lesion.
192 J. A. Coll

Fig. 12.5 Radiographic

view before selective caries
removal mandibular
permanent right first molar

Fig. 12.6 View after

selective caries removal
leaving the deepest caries
in place in the mandibular
permanent right first molar

Maltz et al. [20] published the results of a randomized controlled trial (RCT)
where SW and selective caries removal were compared in 299 permanent molars.
The results of the 3-year follow-up showed a significantly higher success rate of
91% for selective removal compared to SW success of 61%.
Maltz et al. speculated on reasons why stepwise excavation success was only
61% after 3 years. It was noted that some SW patients did not return for the second
appointment at the correct time, and the success rate in these patients was only 13%.
Patients treated with SW that had a final excavation and permanent restoration in
1–2 months had success rates not statistically different from selective removal of
caries (88% SW vs. 91% selective removal).

12.5.4 No Caries Removal

Another type of caries management has been reported only in primary teeth. It
involves no caries removal and placement of a steel crown to seal the caries and stop
the carious process. The technique is termed the Hall technique [21, 22]. The
48-month results [22] showed significantly better success (p = 0.0005) using the
12 Primary and Permanent Teeth Treated with Direct Pulp Capping 193

Hall technique versus complete caries removal and a filling which was usually glass
ionomer.

12.6 Vital Pulp Therapy for Carious Pulp Exposure Having

Normal Pulp or Reversible Pulpitis Diagnosis

12.6.1 Direct Pulp Capping Primary Teeth

Direct pulp capping is ideally done for primary teeth diagnosed as having a normal
pulp. The AAPD 2020 Guideline has a Decision Tree figure showing DPC also
indicated for reversible pulpitis [10]. The caries excavation causes an exposure nor-
mally as a result of using complete caries removal for deep caries. The DPC capping
material is placed on the exposure in an effort to maintain the pulp’s vitality. It is
theorized the DPC will enable the pulp to form tertiary dentin at the exposure site to
form a dentin bridge [23]. DPC procedures in vital primary teeth are indicated for
pinpoint to 1 mm sized mechanical or carious exposures [2]. DPC is contraindicated
in teeth with irreversible pulpitis. The clinical procedure should be done under rub-
ber dam isolation using local anesthesia. The clinical caries is removed using high
and low speed burs and/or hand excavators revealing an exposure (Fig. 12.7). When
an exposure is encountered, the area is preferably rinsed for a DPC with an antimi-
crobial such as sodium hypochlorite (NaOCl) (1–5%) (Fig. 12.8). Then a moistened
cotton pellet with NaOCL is pressed on the pulp exposure for 1–2 min. After

Fig. 12.7 Carious

exposure after complete
caries removal
194 J. A. Coll

Fig. 12.8 Sodium

hypochlorite used to rinse
exposure site

Fig. 12.9 Exposure after

hemorrhage is controlled

hemostasis is obtained, the area is rinsed with saline or water and blotted with dry
cotton pellets to remove the excess saline (Fig. 12.9).
A 2 mm MTA or another bioceramic material is placed over the exposure with a
plastic instrument or amalgam carrier. Calcium hydroxide paste can also be used as
an alternative and was not significantly different in success from alternate capping
agents [1]. If MTA is used, cover it with a resin-modified glass ionomer or a self-
setting glass ionomer before the final restoration.
12 Primary and Permanent Teeth Treated with Direct Pulp Capping 195

The EBD research has shown success of DPC in primary teeth was reported as
88.8% after 24 months [1]. This was based on the combined clinical and radio-
graphic overall success. This evidence at 24 months [1] showed the capping agent
had no significant difference on DPC success. It must be noted that two of the three
24-month studies only included teeth with occlusal caries [1]. In addition, two stud-
ies tested DPC versus indirect pulp cap (IPT) with 12-month results. One study [24]
was a prospective non-randomized design and the other [25] a retrospective design.
Their pooled successes after 12 months were IPT 96% (218/226) and DPC 70%
(14/20). There are three studies comparing DPC using MTA to alternative capping
agents. The results for 12 months showed MTA success at 92% (93/101) and alter-
nate capping agents 89% (89/100) with RR 1.02 (0.95, 1.09) p = 0.67. The alternate
agents were other bioceramic materials or calcium hydroxide.

12.6.2 Direct Pulp Capping Permanent Teeth

DPC in permanent teeth is one method of performing VPT. Bjorndal [19] reported
carious exposures treated with CH for the DPC had success after 1 year of only
31.8%. A systematic review found carious exposures treated with DPC using CH
and MTA had a success rate of 72.9% for teeth followed 3 years or more [3]. A more
recent EBD systematic review and meta-analysis found treating a carious exposure
with DPC was significantly more successful using MTA and Biodentine compared
to calcium hydroxide (CH) [8]. All the included teeth had mature apexes. They
reported DPC using MTA compared to CH after 2- to 3-year follow-up was signifi-
cantly superior (OR 2.21, 95% CI; 1.42–3.44, P = 0.0004). MTA success after
2–3 years was 84% and Biodentine 86%. The pulpal diagnosis of the included teeth
was either normal or reversible pulpitis. Therefore, permanent tooth DPC is indi-
cated for mechanical and carious permanent tooth pulp exposures with immature or
mature apexes having normal or reversible pulpitis.

Figs. 12.10 Carious

exposure before
hemorrhage controlled
196 J. A. Coll

Fig. 12.11 Carious

exposure after hemorrhage
controlled

The method of DPC is similar to that for primary teeth. The treatment should be
under a rubber dam using local anesthesia. The carious tissue is removed usually
employing complete caries removal so that a pulp exposure occurs. It may be a
mechanical or carious exposure (Fig. 12.10). The exposure size of less than 2.5 mm
can be enlarged so it can be rinsed with NaOCL (5.25–6%) [9]. Then a cotton pellet
soaked in NaOCl is used to apply pressure and stop the hemorrhage in less than
6 min [9]. Rinse the area with saline or water and blot dry the exposure site
(Fig. 12.11). Apply MTA or Biodentine or another calcium silicate-based material
to a thickness of 2–3 mm with a plastic instrument or amalgam carrier. Compact the
material with a cotton pellet slightly moistened with water. Cover the material with
a self-setting glass ionomer or resin-modified glass ionomer. Then restore the tooth
with a well-sealed restoration.

12.7 Vital Pulp Therapy for Carious Pulp Exposure Having

Irreversible Pulpitis Diagnosis

A 1-year RCT evaluated four VPT’s using CEM which is a biceramic material for
IPC, DPC, and partial and full pulpotomy [7]. All teeth had a mature apex and caries
in close proximity to the pulp. There were 26% of the 73 DPC teeth diagnosed with
irreversible pulpitis, and all but one had a carious pulp exposure. After 1 year, the
data showed DPC clinical and radiographic combined success was 94.7%. An RCT
in 6–18-year-old children with permanent teeth had caries ¾ into the dentin [26].
Some teeth had a clinical diagnosis of irreversible pulpitis, and all were treated with
DPC using either with MTA or Biodentine. The successes after 18 +/- months were
92.6% for MTA and 96.4% for Biodentine (P > 0.05). The failures were not the
teeth with periapical involvement. The AAE 2021 position paper on vital pulp
12 Primary and Permanent Teeth Treated with Direct Pulp Capping 197

therapy challenged the pulpal diagnosis of teeth that can receive VPT [6]. This
paper cited a study suggesting there is no actual histologic boundary showing a vital
pulp is beyond repair [27]. This would mean a permanent tooth DPC and pulpotomy
could be indicated if it is diagnosed with irreversible pulpitis, either symptomatic or
asymptomatic. The position paper went further by recommending unroofing the
pulp so direct observation of the pulp with a surgical microscope will allow the final
diagnosis. There is no study showing direct visualization of vital pulps allows for a
better pulpal diagnosis for a permanent tooth with deep caries.

12.8 Considerations Before DPC in Primary

and Permanent Teeth

MTA has the potential to cause a gray discoloration while Biodentine and CEM are
reported to cause minimal or no discoloration [7, 26]. Valles [28] reported signifi-
cant color changes in white MTA Angelus and ProRoot MTA due to the bismuth
oxide in the materials. The reason for the discoloration may be the interaction of the
bismuth oxide with NaOCl or blood. In this study, Biodentine exhibited color stabil-
ity for 5 days. Teeth in need of esthetic restorations such as a composite, Biodentine
or another bioceramic restoration, that does not discolor, would be recommended.
The setting time of the bioceramic materials differ and are of clinical importance.
Biodentine has a shorter final setting time (about 10 min) compared to ProRoot
MTA of almost 3 h [29]. There is a setting accelerator added to Biodentine that
speeds up the setting time. MTA’s slower setting time makes its manipulation more
difficult for some compared to Biodentine and other faster setting bioceramic mate-
rials. When using MTA for DPC, it’s best to cover it with a self-setting glass iono-
mer or resin-modified glass ionomer.
In primary teeth, there was no significant difference in DPC 24-month success
reported between MTA and other alternative capping agents and CH [1]. For perma-
nent teeth and primary teeth intended to be retained longer than 24-months, MTA is
likely the better choice. Lin [30] reported bioceramic materials released more cal-
cium and were consistent in raising the pH levels more than calcium hydroxide
materials like Dycal. This article speculated increasing the alkalinity promotes
release of TGF-beta1 from the dentin and promotes reparative dentin formation. In
addition, the calcium hydroxide DPC materials like Dycal are more water soluble
after 90 days and likely diminish its sealing ability [30].
Use of lasers for DPC is still being investigated. In primary teeth, clinical RCT
studies using laser DPC versus other DPC treatments have not been published. In
permanent teeth, there are EBD studies showing shorter-term DPC success with
laser of 92% (24/25) at 12 months [31] and laser-assisted DPC (100% success [32])
where the capping agent may be MTA but a laser was used prior to placing the DPC
agent. At this time, DPC using a laser would need to be at the clinical expertise of
the practitioner after consulting with the patient.
The younger aged patient may be an advantage when doing DPC on permanent
teeth (Fig. 12.12). A retrospective study [33] with a mean follow-up of over 6 years
198 J. A. Coll

Fig. 12.12 Preoperative images maxillary left first permanent molar with preoperative pain in a
12-year-old male

Fig. 12.13 Postoperative

image of #14 with MTA
DPC and composite resin
restoration

found younger aged patients (16–20 years old) had the highest rate of DPC favor-
able treatment using calcium hydroxide (Figure 12.13). The study also found after
6 years, out of 49/199 having unfavorable outcomes, 39/49 (80%) had spontaneous
pain preoperatively.

12.9 Conclusions

• Direct pulp capping in primary teeth is indicated for carious exposures less than
1 mm in size. MTA has a DPC expected success rate of 88% after 24 months in
primary teeth.
• In permanent teeth, direct pulp capping is indicated for carious exposures less
than 2.5 mm when the tooth has no signs or symptoms of irreversible pulpitis.
• Permanent tooth DPC in teeth with irreversible pulpitis has shown 12–18-month
success but longer-term RCT studies are not available.
12 Primary and Permanent Teeth Treated with Direct Pulp Capping 199

• Permanent tooth carious pulp exposures treated with DPC using MTA or
Biodentine have an expected success rate of 84–86% after 2–3 years and are
significantly better than using calcium hydroxide.
• Permanent tooth DPC is indicated for teeth with either immature or mature apexes.

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analysis. Pediatr Dent. 2017;39(1):16–27. E15-E110
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deep caries lesions. Pediatr Dent. 2017;39(5):E146–59.
3. Aguilar P, Linsuwanont P. Vital pulp therapy in vital permanent teeth with cariously exposed
pulp: a systematic review. J Endod. 2011;37(5):581–7.
4. Mente J, Hufnagel S, Leo M, et al. Treatment outcome of mineral trioxide aggregate or cal-
cium hydroxide direct pulp capping: long-term results. J Endod. 2014;40(11):1746–51.
5. American Association of Endodontics. Guide to clinical endodontics. 6th ed. Chicago:
American Association of Endodontics; 2013. 2019 updated.
6. AAE Special Committee on Vital Pulp Therapy. AAE position statement on vital pulp therapy.
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7. Asgary S, Hassanizadeh R, Torabzadeh H, Eghbal MJ. Treatment outcomes of 4 vital pulp
therapies in mature molars. J Endod. 2018;44(4):529–35.
8. Cushley S, Duncan HF, Lappin MJ, Chua P, Elamin AD, Clarke M, El-Karim IA. Efficacy of
direct pulp capping for management of cariously exposed pulps in permanent teeth: a system-
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9. Bogan G, Kim JS, Bakland LK. Direct pulp capping with mineral trioxide aggregate: an obser-
vational study. J Am Dent Assoc. 2008;139:305–15.
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11. American Association of Endodontics. Glossary of endodontic terms. 10th ed. Chicago:
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12. Camp J. Diagnosis dilemmas in vital pulp therapy: treatment for the toothache is changing,
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Pulpotomy for Primary Teeth:
Techniques and Materials 13
Yasmi O. Crystal and Anna B. Fuks

Contents
13.1 Introduction 202
13.1.1 Formocresol 203
13.1.2 Glutaraldehyde 204
13.1.3 Calcium Hydroxide 205
13.1.4 Sodium Hypochlorite 205
13.1.5 Zinc Oxide/Eugenol (ZOE) 205
13.1.6 Ferric Sulfate 206
13.1.7 Lasers 207
13.1.8 MTA and Biodentine 207
13.2 MTA/Biodentine Pulpotomy Procedure and Practical Considerations 209
13.2.1 Pulpotomy of Single Tooth with MTA-Like Material 209
13.2.2 Pulpotomy of Multiple Teeth with Biodentine 213
13.2.3 Is There a New Gold Standard? 216
13.3 Partial Pulpotomy for Primary Teeth 217
13.4 Treatment Planning for a Pulpotomy 217
13.5 Conclusions 219
References 219

Y. O. Crystal (*)
Department of Pediatric Dentistry, College of Dentistry, New York University,
New York, NY, USA
Comprehensive Pediatric Dentistry, Bound Brook, NJ, USA
e-mail: [email protected]
A. B. Fuks
Department of Pediatric Dentistry, Hadassah Medical Center, Faculty of Dental Medicine,
Hebrew University of Jerusalem, Jerusalem, Israel
e-mail: [email protected]

© The Author(s), under exclusive license to Springer Nature Switzerland AG 2023 201
A. B. Fuks et al. (eds.), Contemporary Endodontics for Children and
Adolescents, https://doi.org/10.1007/978-3-031-23980-9_13
202 Y. O. Crystal and A. B. Fuks

13.1 Introduction

In the previous chapters, we have reviewed the importance and benefits of the con-
temporary trends of conservation of form and function, in the case of vital pulp
therapy, through the preservation of primary tooth vitality. The advantages of pre-
serving a tooth in the arch until natural exfoliation followed by immediate replace-
ment by a succedaneous tooth are important at all levels: for control of local
symptoms and restoring function (tooth level), arch spacing (mouth level), for the
child’s well-being (individual level), and for reducing the need for further treatment,
either space maintenance or space management with all the costs they incur (com-
munity level). Minimally invasive approaches, including “selective caries removal
to soft dentin” (indirect pulp treatment) and direct pulp capping, have been dis-
cussed earlier in this book. In this chapter, we will go one step further discussing
pulpotomy as an alternative treatment for vital primary teeth with deep caries.
Pulpotomy is a vital pulp therapy procedure that aims to remove the inflamed/
infected tissue in the coronal pulp chamber and place a medicament that will aid to
restore health and preserve the vitality of the remaining healthy portion of the radic-
ular pulp. The pulpotomy procedure is indicated when caries removal results in pulp
exposure in a primary tooth with a normal pulp or reversible pulpitis or after a trau-
matic pulp exposure, and when there are no radiographic signs of infection or patho-
logic resorption [1]. It has been an effective and widely accepted procedure for the
treatment of teeth with deep caries or trauma for decades.
The efficacy of pulpotomy varies with the materials used, and historically, there
has been a quest for the perfect medicament and/or technique. An ideal pulpotomy
material should control the existing bacterial infection while being biocompatible
with the remaining tissues, capable of inducing hard tissue formation while not
affecting physiologic root resorption, in addition to being affordable. Buckley’s
formocresol was introduced for this purpose in the early 1900s [2]. The use of a
pulpotomy technique was described in 1930 [3] becoming the preferred technique
and gold standard for decades. Because of its limitations and concerns for toxicity
[4], other materials and techniques have been tested and used over the years
(Fig. 13.1 timeline).
These materials are used with different aims as they have different mechanisms
of action on the remaining pulpal tissue. Some of them contain fixing agents (formo-
cresol and glutaraldehyde), others are hemostatic (ferric sulfate), others are antibac-
terial (sodium hypochlorite (NaOCl)), others contain corticosteroids as
anti-inflammatories and antibiotics for bacterial control (Ledermix), and some like
zinc oxide and eugenol (ZOE) were used because of the historical use of eugenol as
a desensitizer. Non-pharmacotherapeutic approaches like electrosurgery and lasers,
aim to cauterize the surface of the remaining radicular pulp tissue to eliminate the
residual infection. Regenerative materials aim at forming a calcium bridge and
inducing reparative dentin. The earliest example of this class, calcium hydroxide
(CaOH)2, had limited success as its increased alkalinity causes inflammation and
necrosis, leading to internal resorption. More recent regenerative, bioactive calcium
silicate cements like mineral trioxide aggregate (MTA), and Biodentine have
13 Pulpotomy for Primary Teeth: Techniques and Materials 203

Fig. 13.1 Pulpotomy materials timeline

stepped up to be not only comparable to the gold standard, but preferable for many
different reasons.
Some of these materials and techniques never gained popularity as they did not
perform clinically as well as formocresol and/or produced undesirable effects like
pulp inflammation, pain, and internal resorption. Some other materials continue to
be used by clinicians despite their limitations, whether it be their lower efficacy or
their undesirable side effects. This chapter does not include descriptions of materi-
als and techniques no longer used like Ledermix and electrosurgery, but we will
discuss the advantages and limitations of the most widely used materials and tech-
niques, including their success rates, considering the results of several recent sys-
tematic reviews which have combined the data of numerous clinical trials performed
in many different countries. Their results include direct or indirect comparisons
between materials that help establish evidence-based recommendations for clini-
cians to have the best chances of success when performing a pulpotomy to manage
primary teeth with deep caries or trauma. It is important that we discuss all of them
in context because although technology continues to develop and with the emer-
gence of new bioactive calcium-silicate cements, current comparative studies have
not yielded enough high-quality evidence to make solid recommendations for a
single gold standard material for pulpotomies on primary teeth.

13.1.1 Formocresol

The formula proposed by Buckley that uses 19% formaldehyde, 35% cresol, and
15% glycerin in distilled water [2] is known as formocresol. Formaldehyde is a fixa-
tive agent that is bactericidal and inhibits enzymes in the inflammatory process. Its
use as a pulpotomy medicament was described in 1930 [3], and the original aim of
using formocresol was to completely fixate all the residual pulp tissue and necrotic
material within the root canal. Recommended initial techniques included a two-visit
204 Y. O. Crystal and A. B. Fuks

treatment where a cotton pellet with full-strength formocresol was left on site in
between appointments, and a one-visit treatment where the cotton pellet with
formocresol was placed on the pulpotomy site for only 5 min. Formocresol was
applied after removing the coronal portion of the pulp and achieving hemostasis,
and after its application the pulp chamber was filled with ZOE, and final restoration
was placed. Histologic findings on these techniques highlight its cytotoxicity, which
ranges from slight inflammation to total degeneration and necrotic changes of the
remaining pulp tissue [5]. As a result, internal resorption and periapical and furca-
tion radiolucencies were often found on treated teeth [6].
In an attempt to reduce the cytotoxicity of full-strength formocresol, later studies
found that using a one-fifth dilution was still effective and led to better clinical
results [7]. Current techniques support limiting both dose and contact time as they
aim to create only a superficial layer of fixation while preserving the vitality of the
deeper radicular pulp. In addition to using a one-fifth dilution, the cotton pellet is
pressed into a cotton roll before application to remove excess and limit the amount
placed on the surface of the remaining pulp stump.
Historically, studies using formocresol as a pulpotomy agent report success rates
ranging from 55% to 95% depending on the application protocol, the study design,
the parameters for defining the success of the treatment, and the length of follow-up.
A recent umbrella review of nine systematic reviews reports a formocresol mean
clinical success rate of 99% and the radiographic success of 85% over a 24-month
period [8]. These figures include the results of a systematic review comparing medi-
caments that reported that MTA pulpotomy was superior to formocresol. Compared
with formocresol, MTA reduced both clinical and radiological failures, with a sta-
tistically significant difference at 24 months for radiological failure. Another recent
systematic review [10] found that compared to formocresol, Biodentine had signifi-
cantly lower clinical and radiographic failures over a period of 12 months.
These new results are very important because the potential systemic toxicity of
formocresol has been a concern over the years. Cresol is locally destructive to vital
tissues but presents negligible potential for systemic distribution following the pulp
treatment technique. However, formaldehyde is distributed systemically after the
pulp treatment technique, so its potential systemic toxicity has been a topic of
debate for decades [11]. The fact that it is classified by the International Agency for
Research on Cancer (IARC) of the World Health Organization (WHO) as a known
human carcinogen (IARC 2017) has resulted in its decreased popularity worldwide.
Despite all this, its high clinical efficacy, affordability, and availability have kept it
in use in certain areas, as until recently, no other materials had proven to be equal or
better. This may be changing currently with the advent of more affordable biocom-
patible materials that will be discussed in this chapter.

13.1.2 Glutaraldehyde

Glutaraldehyde is a dialdehyde that was proposed as an alternative fixative to formo-

cresol because of its potential lower toxicity and better tissue fixative properties,
13 Pulpotomy for Primary Teeth: Techniques and Materials 205

despite the disadvantage of having a very short shelf life. Clinical studies using 2%
glutaraldehyde applied for 1–5 min showed clinical success ranging from 90% over
18 months [12] to 88% over 24 months [13].
Its cytotoxicity was reported to be similar to formocresol, and a large number of
treated teeth presented with internal resorption. With less clinical success than
formocresol and questionable improved safety, studies have not justified recom-
mending 2% glutaraldehyde to substitute for formocresol [13].

13.1.3 Calcium Hydroxide

Calcium hydroxide (Ca(OH)2) has been in use since the 1930s and was proposed as
a pulpotomy medicament because of its potential to induce reparative dentin and
pulp healing [14]. However, studies have shown lower rates of success for calcium
hydroxide pulpotomies since it was first used, ranging from 31% to 90% [15–17].
This variation could be due to the inclusion criteria for the studies, the wide varia-
tion of preparations used, and the follow-up time. Most failures are due to chronic
inflammation that led to clinical and radiographic failures. The main drawbacks of
Ca(OH)2 are associated with its physical properties, as this non-setting material will
go through degradation and dissolution over time, leading to infection and/or inter-
nal resorption. A more detailed description of calcium hydroxide can be found in
Chap. 17. In recent systematic reviews comprising many prospective clinical stud-
ies, calcium hydroxide pulpotomies are reported to have a clinical success rate of
46% [8], which is significantly less successful than formocresol, ferric sulfate, and
MTA, resulting in the recommendation against the use of calcium hydroxide as a
pulpotomy medicament [9, 18, 19]

13.1.4 Sodium Hypochlorite

Sodium hypochlorite has been utilized as an irrigant during endodontic treatment

due to its antibacterial properties while causing minimal pulpal inflammation in the
remaining tissue [20]. For this reason, its use at 3–5% concentrations placed in the
pulp chamber on a cotton pellet for 30 s was tested in several clinical studies, show-
ing success rates comparable to ferric sulfate and formocresol at 12-month follow-­
ups [21]. However, available clinical studies with 18 and 24 months of follow-up
show lower success rates than those of formocresol pulpotomies [19, 22]. With cur-
rent better alternatives that offer better clinical and radiographic success, the use of
sodium hypochlorite as an isolated medicament for pulpotomy has fallen into disuse.

13.1.5 Zinc Oxide/Eugenol (ZOE)

In search of non-aldehyde pulp therapy alternatives, several retrospective studies

have reported using ZOE as a stand-alone medicament for pulpotomy with clinical
206 Y. O. Crystal and A. B. Fuks

success rates comparable to formocresol when placing it after achieving hemostasis

and immediately followed by a stainless steel crown (SSC) restoration [23, 24].
Historically it has been one of the most frequently used materials in dentistry due to
its sedative and palliative properties in cases of pulpal pain [25]. However, diverse
toxic effects have been reported when it is directly applied over the pulp since euge-
nol induces a chronic inflammatory response and inhibits the immune reaction of
pulp defense [26] and increases the risk of internal resorption. Clinical studies
report internal resorption in approximately 27% of teeth followed up at 24 months
[27]. Retrospective studies show clinical success rates of over 90% at different time
periods [28, 29]. However, more recent prospective studies with clinical and radio-
graphic data show a success rate of 65% over a 24 month period, which is signifi-
cantly lower than most other available pulpotomy materials, therefore making it
unsuitable as a medicament of choice [19].

13.1.6 Ferric Sulfate

Ferric sulfate (FS) is a hemostatic agent that has traditionally been used for bleeding
control. Its use was promoted as a pulpotomy agent to induce quick hemostasis and
prevent clot formation, therefore improving the performance of whatever material
was placed in the pulp chamber after it. Clinical studies using a 15.5–16% concen-
tration have reported success rates similar to formocresol [30–33], with many of the
reported failures being a result of internal resorption, leading to early exfoliation.
The internal resorption has been attributed to the interaction of ferric ions and free
release of eugenol from the ZOE used to cover the pulp stumps after hemostatic
control with FS [34] as ZOE placed directly over the pulp tissue is reported to cause
chronic inflammation that increases the risk of internal resorption [27]. A recent
umbrella review of nine systematic reviews reports the efficacy of ferric sulfate
ranging from 70 to 100% with clinical success always being higher than radio-
graphic success at 24 months [8]. Success rates decrease at longer follow-up peri-
ods: one study reported 62% success at 36 months [35], and systematic reviews in
the past have reported the superiority of MTA over FS [36, 37]. Although a recent
systematic review [34] concludes that the clinical and radiographic outcomes of
MTA and FS were not different at 24-month observation periods, they included
studies with a high risk of bias, and their forest plots favor MTA over FS for radio-
graphic success without reaching statistical significance. When including only low
risk of bias prospective studies comparing ferric sulfate to currently available bio-
compatible materials, a more recent systematic review [19] reported the success of
MTA being significantly higher than that of ferric sulfate at 24-month follow-ups.
They report a clinically significant NNT (number needed to treat) of 5, which means
that after doing five MTA pulpotomies, a dentist would prevent one failure if FS had
been used.
Ferric sulfate continues to be used as it presents comparable clinical success to
formocresol, but with fewer concerns about toxicity. With MTA and other biocom-
patible materials showing better performance over longer follow-up periods with
13 Pulpotomy for Primary Teeth: Techniques and Materials 207

fewer radiographic signs of potential failures, they may present as a better option
depending on the specific clinical situation.

13.1.7 Lasers

The use of lasers for pulpotomy was introduced as this technique could bypass the
toxicity [38] and secondary effects of chemotherapeutic agents, with benefits
including bleeding control and sterilization, to eliminate residual infection pro-
cesses that would improve pulp cell healing promotion [39]. Several different lasers
have been used in pulpotomy procedures in primary teeth including CO2, Nd:YAG,
InGaAIP, Er:YAG, and diode lasers, with the latter one being the most commonly
reported laser for pulp therapy in children [40]. The clinical and radiographic suc-
cess of laser pulpotomies ranges from 90% at 12 months to 93% at 24 months [41].
A systematic review on lasers reports that the laser technique shows comparable
clinical and radiographic results to other conventional pulpotomy medicaments
including formocresol and MTA after 18 months [40]. However, studies are typi-
cally small and with limited follow-up periods to make accurate comparisons [19].
More studies are required to confirm if and what kind of laser therapy can be an
acceptable choice for a chemical-free option for a successful pulpotomy. Laser
wavelength and other characteristics will need to be carefully defined.

13.1.8 MTA and Biodentine

The introduction of new bio-inductive and regenerative dental materials has

improved the likelihood of finding better medicaments for pulp therapy as has been
described in Chap. 11. The earliest material, mineral trioxide aggregate’s (ProRoot
MTA, Dentsply) main components include tricalcium silicate, dicalcium silicate,
bismuth oxide, tricalcium aluminate, calcium sulfate dihydrate (gypsum), and cal-
cium aluminoferrite, and their combination produces a colloidal gel that solidifies
into a hard cement that induces the formation of dentin, cement, and bone [42].
Bismuth oxide is added for radiopacity, and calcium compounds react with the
humid environment, releasing calcium hydroxide at decreasing rates over time. This
results in a high pH of 12.5 that is inhospitable for bacterial growth and results in a
prolonged antibacterial effect. Unlike calcium hydroxide products, it sets com-
pletely in the presence of moisture and has very low solubility, maintaining a hard,
excellent marginal seal. It produces significantly effective dentinal bridging in a
shorter time period with significantly lesser inflammation and pulpal necrosis than
earlier similar regenerative materials like calcium hydroxide. MTA has been widely
recognized as a superior material for vital pulp therapy because of its biocompatibil-
ity, good sealing properties, antimicrobial activity, and ability to set in the presence
of moisture and blood. Its main drawbacks are its handling characteristics (long
setting time of 3–4 h), discoloration of surrounding tissues, low radiopacity, incom-
patibility with other dental materials when layered, and higher cost [42]. Its success
208 Y. O. Crystal and A. B. Fuks

rates as a pulpotomy agent have been described in numerous studies showing supe-
riority over most other materials [9, 19, 43]
White MTA was developed to overcome the discoloration caused by the original
ProRoot MTA, while showing comparable biocompatibility and success rates [44].
To overcome other disadvantages of original MTA, less expensive alternative bioc-
eramic materials such as MTA Angelus (Angelus, Londrina, Brazil) with setting
time of 10–15 min, MedCem-MTA Portland Cement (MedCem GmbH, Weinfelden,
Switzerland) with zirconium oxide added as radiopacifier, and many others have
been developed. Prospective studies of these products show no significant differ-
ence between clinical and radiographic outcomes when compared to the original
compound [44, 45]. Another alternative calcium-silicate material, Biodentine
(Septodont, Saint Maur-des-Fosses, France), has also been well studied in clinical
trials. It is composed of tricalcium silicate cement, zirconium oxide, and calcium
carbonate. With good biocompatibility and bioactive behavior, it stimulates [46]
reparative dentin and dentin bridge formation, anchoring the material microme-
chanical to the underlying dentin. It is presented in a capsule with easy handling that
sets in approximately 12 min and does not cause tooth discoloration. Its main draw-
back is poor bonding to the overlying resin restoration. Biodentine has shown higher
success rates than formocresol [10, 47] and similar success rates to MTA in clinical
trials [48–50]. Other new bioactive materials with different compositions aim to
have better handling capabilities, compatibility to overlaying materials, minimal
staining, and low cost [42]. Some of these materials, including NeoMTA2 and
NeoPUTTY (Nusmile, Houston, TX, USA) which provide easy handling and low
waste, TheraCal LC (Bisco, Schaumburg, Ill, USA) a light-cured resin-modified
tricalcium silicate [51], and CEM cement (CEM, BioniqueDent, Tehran, Iran) a
calcium-enriched mixture [52], and many others, are favored by clinicians around
the world for their ease of handling and affordability. However, few or no long-term
prospective clinical studies have been published to substantiate the claims that these
materials’ efficacy and biocompatibility are indeed comparable to MTA [42]. With
many studies ongoing, the future looks hopeful for finding suitable substitutes
for MTA.
A recent systematic review reports that Biodentine had significantly lower clini-
cal and radiographic failure rates than formocresol (FC) at 12 months [10]. Several
other systematic reviews report that MTA pulpotomy was superior to FC and FS,
and all three treatments may be superior to CH pulpotomy [8, 9, 19]. Compared
with FC, MTA reduced both clinical and radiological failures, with a statistically
significant difference at 24 months for radiological failure. Compared to FS, MTA
reduced radiographic failures at 24 months. Compared with CH, MTA reduced both
clinical and radiological failures, with a statistically significant difference for clini-
cal failure at 24 months [19]. This systematic review reported a 24 month success
rates of 94% for MTA and 90% for Biodentine [19], while other systematic reviews
have reported similar results at 24 months [8] and 18 months [46], concluding that
this small difference has no clinical significance, as both materials have similar
efficacy, and can be used safely according to the clinical situation and dentist’s
preference.
13 Pulpotomy for Primary Teeth: Techniques and Materials 209

13.2 MTA/Biodentine Pulpotomy Procedure

and Practical Considerations

With the use of local anesthesia, rubber dam and following complete caries removal,
amputation of the coronal pulp, and attaining hemostasis, the pulp stumps are cov-
ered with MTA-like material prepared according to the manufacturer’s instructions.
The material is introduced carefully into the prepared cavity, avoiding trapped air
bubbles and condensed using a wet sterile cotton pellet to ensure good adaptation to
the cavity walls and margins in a layer of approximately 2 mm. After condensation,
the MTA-like material can be covered with a less expensive alternative considering
compatibility with the final restoration planned for that tooth, as illustrated in the
following figures.

13.2.1 Pulpotomy of Single Tooth with MTA-Like Material

Figures 13.2, 13.3, 13.4, 13.5, 13.6, 13.7 and 13.8 illustrate the clinical procedure
for a pulpotomy on a single tooth with a pre-mixed calcium silicate cement.

Fig. 13.2 Primary molar

with deep caries and
suspected caries exposure.
Local anesthesia is applied
and the tooth is isolated
with a rubber dam
210 Y. O. Crystal and A. B. Fuks

Fig. 13.3 After complete

caries removal, pulp is
exposed, roof of the pulp
chamber is removed, and
pulp tissue is completely
removed

Fig. 13.4 Hemostasis is

achieved using a cotton
pellet (dry or moist with
saline or water)
13 Pulpotomy for Primary Teeth: Techniques and Materials 211

Fig. 13.5 Visible pulp

canals after achieving
hemostasis

Fig. 13.6 Mix or prepare

MTA-like material as per
manufacturer’s
instructions. Illustrated is a
pre-mixed, no-waste brand
212 Y. O. Crystal and A. B. Fuks

Fig. 13.7 MTA-like

material is placed and
condensed with a sterile
wet cotton pellet, avoiding
bubbles, ensuring complete
coverage of the pulp canals
and adaptation to the
cavity walls in a 2 mm
layer

Fig. 13.8 MTA-like 2 mm

layer is then covered with
glass ionomer cement, or
ZOE, ensuring
compatibility of the
material with the final
restoration
13 Pulpotomy for Primary Teeth: Techniques and Materials 213

13.2.2 Pulpotomy of Multiple Teeth with Biodentine

Figures 13.9, 13.10, 13.11, 13.12, 13.13, 13.14, 13.15 and 13.16 illustrate the clini-
cal procedure for pulpotomies on multiple teeth with a pre-mixed calcium silicate
cement (Biodentine).
The methods used for caries removal (bur or chemical), form of coronal pulp
removal (bur or curette), hemostasis (dry or moist cotton pellet), and irrigation
(water or saline) have not been found to have a significant impact on the success of
the pulpotomy [19], so clinicians are encouraged to use their preferred techniques.
ZOE has traditionally been the material of choice for pulp chamber filling after
pulpotomy is performed with materials including formocresol, ferric sulfate, or
sodium hypochlorite. MTA and other similar materials create an excellent seal, but
their high cost may limit the amount used at each procedure, so ZOE, reinforced
ZOE, glass ionomers, or RMGIs can also be used to seal the rest of the pulp cham-
ber without compromising treatment outcomes [19], as discussed in detail in
Chap. 15.

Fig. 13.9 Molars with

deep caries in proximity to
the pulp suspected of
carious exposure, after
local anesthetic and rubber
dam isolation

Fig. 13.10 Caries is

removed completely and
roof of the chamber is
removed, as well as all
pulp tissue in the chamber,
exposing orifices of pulp
canals
214 Y. O. Crystal and A. B. Fuks

Fig. 13.11 Orifices for

the pulp canals are visible
after achieving hemostasis
with cotton pellet

Fig. 13.12 Biodentine is

mixed according to
manufacturer’s instructions

Fig. 13.13 Biodentine is

placed in the pulp chamber
13 Pulpotomy for Primary Teeth: Techniques and Materials 215

Fig. 13.14 Material is

condensed with a sterile
wet cotton pellet, avoiding
bubbles, ensuring complete
coverage of the pulp canals
and adaptation to the
cavity walls

Fig. 13.15 Material in

one capsule is enough to
completely fill the whole
pulp chamber of several
teeth

Fig. 13.16 Final

restoration is placed,
preferably on the same
visit. Full preformed
crowns are the preferred
restoration on multi-­
surface lesions to ensure
adequate seal
216 Y. O. Crystal and A. B. Fuks

The high cost of the original MTA had traditionally been cited as the biggest bar-
rier for its widespread use. As an example of this, one cost-effectiveness study in the
UK cited it to be GBP 60 (approx. US $80) per pulpotomy at the time of the study
2006–2012 [53]. But new MTA-like materials that are more affordable may change
the stage. A recent in vitro study [54] estimated the price of a treatment/dose of
alternative MTA materials, when used in 2 mm layers over the pulp stumps. They
report that the cost/dose of Biodentine is approx. $14.49, compared to $4.68 for
NuSmile NeoMTA, $4.68 for New MTA Plus, $5.71 for MTA Angelus, and $13.75
for MTA-Flow. Their study cites the cost of gray ProRoot MTA is $26.51 and white
ProRoot MTA is $31.25 (with prices calculated from companies’ websites in 2017).
They also calculate the cost of the material used for pulp chamber filling, and when
combined, they report that NeoMTA-type cements and IRM powder-liquid base
were the most affordable combination, being 3.5 less costly than using a bioceramic
material followed by RMGI when used for a single pulpotomy. When multiple pulp-
otomies are done on the same visit (as may be the case with sedation or general
anesthesia cases), the cost of Biodentine is lower, as one capsule can be used for
multiple teeth filling the whole pulp chamber. Although only one of the factors to
consider when planning for a pulpotomy, these price comparisons together with
availability of the products are all important for the clinician to consider when
choosing a material for pulpotomies in different settings. (See Chap. 11.)

13.2.3 Is There a New Gold Standard?

An umbrella review of systematic reviews reported that the highest quality of evi-
dence for pulpotomy medicaments supports the effective application of MTA and
formocresol [8]. The American Academy of Pediatric Dentistry (AAPD) guideline
published in 2017 only recommended MTA and formocresol as medicaments of
choice for primary teeth expected to be retained for 24 months or more, and they
recommended against the use of calcium hydroxide. Other treatments, such as ferric
sulfate, lasers, sodium hypochlorite, and tricalcium silicate, received only condi-
tional recommendations [55]. A 2018 Cochrane review [9] concludes that MTA
may be the most efficacious medicament to heal the root pulp after pulpotomy of a
deciduous tooth and recommended more research to confirm an acceptable second
choice, to overcome the toxicity concerns of formocresol.
As more recent randomized controlled trials including new materials are pub-
lished, our knowledge may advance. A recent 2022 systematic review [19] per-
formed a network meta-analysis to determine the rankings of the four top
medicaments for pulpotomy success. Their results are that MTA was best, followed
by Biodentine second, third was formocresol, and lowest was ferric sulfate. MTA
was not significantly different from Biodentine but was significantly better than
formocresol and ferric sulfate [19].
So which medicament should a clinician choose for pulpotomies? It seems from
the latest research that MTA, Biodentine, and similar biocompatible materials offer
the best efficacy at longer periods of observation and therefore, should be the
13 Pulpotomy for Primary Teeth: Techniques and Materials 217

obvious choice. Although formocresol was the gold standard for decades, and its
clinical efficacy had made it acceptable for a long time, toxicity concerns limit its
use in many settings and many dental schools in the US and Europe no longer list it
as the main agent taught and used for pulpotomy [56, 57], which will certainly have
an impact on its future utilization. But long-term efficacy may not be the only factor
a clinician is looking for when deciding on a pulpotomy medicament. The age of the
patient and time of expected tooth survival may also come into play, together with
affordability and availability of materials when deciding which material to use. It is
up to the clinician to weigh in all factors including their own preferences and experi-
ence, to determine which choices are best for the specific situation, and to then
explain to the parents the available options to obtain informed consent.
It is also important for the clinician to consider that the cost-effectiveness of the
materials per tooth treated with pulpotomy may not be a determinant factor for cost
savings in their overall practice. Studies have shown that the use of selective caries
removal and indirect pulp therapy have significantly reduced the number of pulp-
otomy procedures without an increase in the number of abscessed teeth or extrac-
tions as a result [58]. With less pulpotomies performed, the cost of the material used
could be slightly increased to a choice that can offer better success rates, without
compromising cost-effectiveness.

13.3 Partial Pulpotomy for Primary Teeth

Partial pulpotomy is a procedure where only 1–2 mm of pulp tissue adjacent to the
pulp exposure site are removed and the medicament is placed on presumably healthy
tissue [59].
Partial pulpotomy for primary teeth has been a procedure described in numerous
case reports, usually after trauma on anterior teeth, with varied success rates depend-
ing on the material used. One clinical study compared calcium hydroxide for partial
pulpotomy for carious exposures on primary molars to formocresol pulpotomies
and reported results of 74% success rates, similar to formocresol pulpotomy over
36 months [60]. Another randomized controlled trial that reports this technique for
caries exposure on primary molars comparing MTA partial pulpotomy to formocre-
sol pulpotomy reported overall success rates of 82% for MTA partial pulpotomy and
95% for formocresol pulpotomy over 24 months [61]. With the limited number of
studies and the availability of better techniques and materials for pulpotomy with
higher success rates over time, there is not enough evidence to recommend partial
pulpotomies on primary teeth.

13.4 Treatment Planning for a Pulpotomy

Throughout the book, we have emphasized that diagnosis is crucial for the success
of pulp therapy, and this is most important when planning for a pulpotomy. History
of spontaneous pain, sensitivity to percussion, mobility of the tooth, presence of
218 Y. O. Crystal and A. B. Fuks

sinus tract, or radiographic evidence of pathosis indicate that the inflammatory pro-
cess has progressed beyond the confines of the involved tooth into adjacent tissues
in which case, the likelihood for a successful pulpotomy is poor.
An umbrella review that included 9 systematic reviews published between 2014
and 2020 including 96 studies on different pulp treatments reported that at
24 months, indirect pulp capping had the highest success rate (94%), followed by
direct pulp capping (88.8%), with different medicaments not significantly affecting
the outcome. Pulpotomy showed the lowest success rate when all materials were
evaluated together (82.6%) [8]. However, a more recent systematic review [19] that
included new RCTs using bioactive calcium silicate cements and using only high-­
quality evidence found that IPT had 97% and 96% success at 24 and greater than
36 months, compared to pulpotomy, which showed 95% and 94% success at 24 and
greater than 36 months. This slight difference was not found to have clinical signifi-
cance, therefore recommending that both, IPT or pulpotomy using bioactive cal-
cium silicate cements, are likely to have similar high success rates.
This new evidence is still consistent with the direction of this book, where we
stress a conservative and biological approach to pulp therapy due to its consistent
long-term results, but when considering the option of a pulpotomy, choose bioactive
materials that are more likely to improve success over time.
It is evident that the indications for indirect pulp therapy are very similar to those
for a pulpotomy: a vital primary tooth with deep caries and without signs of symp-
toms of irreversible pulpitis or necrotic pulp. If the indications are similar between
both options, and it is recommended that a conservative approach should be taken,
the clinician should first opt to choose indirect pulp treatment using selective caries
removal to avoid pulp exposure whenever possible. So, when should a pulpotomy
be chosen as the best treatment for a tooth, when establishing a comprehensive
treatment plan?
Accurate pulp diagnosis is crucial for the success of vital pulp therapy. In young
children, it is especially difficult to obtain an accurate diagnosis of vitality on a
tooth with very deep caries, as pulp testing including cold and electric tests have
shown to be reliable only in children older than 7 years [62], and history of pain may
not give contributory information. Sometimes reference to pain may come from
food impaction and not exclusively from pulpal origin. Clinical signs and symptoms
(absence of pain to percussion and palpation) and radiographic evidence of healthy
root, periodontal tissues, and periradicular bone aid ruling out pulp necrosis. But
when the pulpal diagnosis is uncertain, that is, if radiographic decay shows the pos-
sibility of the decay process involving directly the pulp chamber in absence of a
diagnosis of irreversible pulpitis or pulp necrosis, treatment planning a pulpotomy
procedure may be a good option to verify the vitality of the pulp. This is especially
the case if the child’s cooperation requires advanced forms of behavior management
like sedation or general anesthesia, since the option of retreating from a failed indi-
rect pulp therapy would be complicated by the behavior challenge. Once caries
removal has been completed with the result of a carious pulp exposure and the pulp
chamber has been accessed, the clinician can evaluate the bleeding during pulp tis-
sue removal and subsequent hemostasis to use as additional information to assess if
13 Pulpotomy for Primary Teeth: Techniques and Materials 219

the radicular pulp may already be affected to confirm if pulpotomy is the best option,
or if pulpectomy should be the treatment of choice.
In addition to an accurate diagnosis of pulpal status and the biological effect and
success of the pulpotomy agent, obtaining a complete seal of the vital pulp from the
oral environment is the third crucial element for the success of a pulpotomy.
Therefore, the isolation used, the material used over the pulpotomy, the restoration
type, and the experience of the clinician are factors that matter. The use of rubber
dam isolation is considered the standard of care. Either a ZOE material, GI cement,
or RMGI can be used over the pulpotomy agent providing adequate seal. Preformed
metal crowns (PMCs or SSCs) seem to be the best option after pulpotomy, espe-
cially in multi-surface lesions. All these factors should be considered in light of the
child’s expected cooperation for treatment when planning for a pulpotomy. Ideally
the final restoration should be completed on the same visit, however leaving the
chamber sealed with ZOE, GIC, RMGI, or Biodentine as temporary fillings and
completing the final restoration at a second visit do not seem to affect the success of
the pulp therapy [19].

13.5 Conclusions

Our better understanding of the healing capacity of pulp tissue has changed the way
we approach pulp therapy allowing us to use more conservative methods. When it
comes to pulpotomy, the advent of new biocompatible and more affordable materi-
als has improved our expectations of pulpotomy treatment allowing us to move
forward after a century of compromising with materials with notable disadvantages.
Bioactive calcium silicate materials (like MTA and Biodentine) have proven to have
superior results over all other pulpotomy materials, and clinicians are encouraged to
use them as the preferred medication for pulpotomies whenever possible.
Still, diagnosis, case selection, and proper management are key to the success of
pulpotomy treatment. Future high-quality research based on uniform standards may
present us with the evidence required to arrive at stronger recommendations and
guidelines for pulpotomy treatment in the coming years.

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Non-Vital Pulp Therapies in Primary
Teeth 14
Moti Moskovitz and Nili Tickotsky

Contents
14.1  Morphological Considerations 224
14.2  Primary Tooth Root Canal Physiology 224
14.3  Primary Tooth Root Canal Anomalies 228
14.4  Pulpal and Periapical Diagnostics 229
14.5  Indications for Pulpectomy 229
14.6  Contraindications for Pulpectomy 230
14.7  Pulpectomy Procedures 230
14.7.1 Access and Debridement 230
14.7.2 Root Canals Irrigation 232
14.7.3 Filling the Root Canal(s) 234
14.8  Supplementary Methods 237
14.8.1 Electronic Apex Locators 238
14.8.2 Ultrasonic Instrumentation 238
14.8.3 Lesion Sterilization Tissue Repair (LSTR) 238
14.9  Evaluation of Pulpectomy 239
14.10 Adverse Effects of Pulpectomy 241
14.11 Adjunctive Systemic Antibiotic Treatment 241
References 242

M. Moskovitz (*)
Department of Pediatric Dentistry, Hadassah Medical Center, Faculty of Dental Medicine,
Hebrew University of Jerusalem, Jerusalem, Israel
e-mail: [email protected]
N. Tickotsky
The Goodman Faculty of Life Sciencee, Bar Ilan University, Ramat Gan, Israel

© The Author(s), under exclusive license to Springer Nature Switzerland AG 2023 223
A. B. Fuks et al. (eds.), Contemporary Endodontics for Children and
Adolescents, https://doi.org/10.1007/978-3-031-23980-9_14
224 M. Moskovitz and N. Tickotsky

14.1 Morphological Considerations

A major challenge for the clinician performing root canal treatment in primary teeth
is the teeth’s morphology. The primary dentition root and canal morphology includes
a large range of anatomical alterations and is unpredictable [1, 2]. A new coding
system for classifying the roots, canals, and developmental anomalies has been
introduced recently [3]. This classification provides detailed information on tooth
description, numbers of roots, and root canal configuration in addition to accessory
canals and tooth anomalies [3].
Root canal configurations change dynamically with increasing age as the deposi-
tion of dentine and physiologic root resorption alter the morphology of the root
apex, leading to difficulty in working length determination. Accessory canals are
common in the primary dentition, especially in the furcation area [4–8]. Treatment
of accessory canals in a clinical setting is advisable only when the primary tooth is
not about to exfoliate or if there are no signs of extensive root resorption.

14.2 Primary Tooth Root Canal Physiology

Incisors and canines are usually single rooted with a single root canal [8] but acces-
sory roots and root canals in primary anterior teeth have been documented [3].
Primary maxillary central and lateral incisors normally have a single conical or
triangular-­shaped root and a large single canal while primary maxillary canines
normally have a single, triangular-shaped root and a large single canal. Primary
mandibular canines typically have a single, conical root that tapers toward the lin-
gual and a large single canal [8]. Primary anterior teeth after pulpectomies had a
higher survival rate than primary molars [9].
Primary maxillary molars (Fig. 14.1) may have two to four roots, with the
three-rooted variant being the most frequent. Fusion of the distobuccal (DB) root
with the palatal root is also common as a double-rooted variant [8]. The prevalence
of a second mesiobuccal (MB) root canal can be as high as 95% [10]. The palatal
root is the longest and is curved, followed by the MB root. The DB root is the short-
est and smallest in diameter of the three roots [8]. The maxillary primary first
(Fig. 14.1) and second (Fig. 14.2) molars have three divergent and separated roots
[1]. Maxillary first molars have three canals, and second molars have either three
(70.9%) or four canals (29.1%).
The primary maxillary second molar (Fig. 14.2) normally has three roots that are
widely separated. The palatal root is the longest followed by the MB root. The DB
root is the shortest and roundest of the three roots. Each root usually contains a
single canal system [8]. In maxillary molars, the double root variant with fusion
between both the distobuccal and palatal roots is the predominant type, in the first
molar it ranges from 60 to 77%, and in the second molar it is 22.5% [11]. In the
mesiobuccal roots of the maxillary molars, a double canal system was observed [12].
While primary second molars, both in the maxilla and in the mandible, are more
accessible than first molars, all of them are negotiable [13].
14 Non-Vital Pulp Therapies in Primary Teeth 225

Fig. 14.1 Maxillary first primary molar, internal morphology (upper row, buccal occlusal and
palatal view; lower row, mesial and distal views)

Primary mandibular molars (Figs. 14.3 and 14.4) can have one to four
roots; the double-rooted variant is the most common [8, 12, 14]. Two canals in
the mesial root and one canal in the distal root comprise the most observed ana-
tomical configuration [14]. Internal and external morphology of the primary
mandibular first molar (Fig. 14.3) closely resembles that of the primary mandibu-
lar second molar (Fig. 14.4) [1]. Mandibular primary first molars have either
three canals (79.2%) or four canals (20.8%), and all second molars have four
canals [13]. A double canal system was observed in the mesial roots of the man-
dibular molars [12].
It is important to note that documented root canal morphology varies with the
diagnostic aid used (e.g., Cone beam CT) and in different ethnic popula-
tions [11].
226 M. Moskovitz and N. Tickotsky

Fig. 14.2 Maxillary second primary molar, internal morphology (upper row, buccal occlusal and
palatal view; lower row, mesial and distal views)
14 Non-Vital Pulp Therapies in Primary Teeth 227

Fig. 14.3 Mandibular first primary molar, internal morphology (upper row, buccal occlusal and
palatal views; lower row, mesial and distal views)
228 M. Moskovitz and N. Tickotsky

Fig. 14.4 Mandibular second primary molar, internal morphology (upper row, buccal occlusal
and palatal views; lower row, mesial and distal views)

14.3 Primary Tooth Root Canal Anomalies

Unusual and complicated morphology of the primary tooth root canals make clean-
ing and shaping them difficult and reduce the success of root canal therapy for pri-
mary teeth [15]. The physiologic procedures of root resorption, which starts soon
after the complete formation of the root, and the continuous formation of secondary
dentine, modify the root canal system over time. The resorptive process along the
root surface is uneven and is subject to continuous morphological changes [16].
14 Non-Vital Pulp Therapies in Primary Teeth 229

Nearly 83% of extracted primary molars had at least one accessory canal in the
furcation area (chamber/furcation canals) [3]. Mesial and distal roots of primary
second mandibular molars have lateral canals [17]. Only a small number of those
canals are patent, and the majority usually terminate within the root dentine.
Another anatomic root variation in molars is the presence of extra roots. Primary
mandibular first molars usually have one mesial and one distal root, but rarely an
additional third root (supernumerary root) is seen. When it is located distolingually
to the main distal root, it is called “radix entomolaris (RE)” [18, 19], and when it is
placed mesiobuccally to the mesial root, it is called “radix paramolaris (RP)” [20].
Anatomic variations such as taurodontism [21], root fusion, dens invaginatus [22],
enamel pearls [23], and C-shaped canals have been seen in mandibular molars.

14.4 Pulpal and Periapical Diagnostics

Pulp condition should be evaluated based on the clinical signs and symptoms the
patient presents with, and on oral and radiographic examination, as explained below
and in Chap. 9. Pre-and post treatment radiographic control is crucial [24].

14.5 Indications for Pulpectomy

A pulpectomy is indicated in primary teeth with irreversible pulpitis or necrosis.

Clinically, a tooth in which the pulp chamber has been opened (for pulpotomy) and
the radicular pulp exhibits clinical signs of irreversible pulpitis or pulp necrosis
(e.g., suppuration, purulence) will require a pulpectomy. Radiographic examination
of the roots should exhibit minimal or no resorption. When there is no root resorp-
tion present, pulpectomy is recommended over lesion sterilization tissue repair
(LSTR) [25, 26]. Pulpectomy is a viable long-term treatment for non-vital teeth
without root resorption compared to those with root resorption. Therefore, pulpec-
tomy should be considered for non-vital primary teeth without preoperative root
resorption [26].
Diagnosis of irreversible pulpitis cannot be based solely on pulp tissue bleeding
that cannot be controlled within 5 min [27] and needs to be based on at least one of
the signs or symptoms that indicate irreversible pulpitis or pulp necrosis in primary
teeth: unprovoked toothache, sinus tract or other soft tissue pathology, gingival
swelling not associated with periodontal disease, abnormal tooth mobility, radio-
graphic furcation or periapical radiolucency, or external or internal root resorption
[27, 28].
Pathological changes in alveolar bone because of pulpal inflammation typically
are located in the furcation region of the primary molars as opposed to the perira-
dicular region in the permanent molars [8].
230 M. Moskovitz and N. Tickotsky

14.6 Contraindications for Pulpectomy

In non-vital primary teeth, the clinician should choose extraction over non-vital
pulp therapy for teeth deemed non-restorable that have an inadequate crown or
extensive root structure resorption.
Unrestorable teeth are characterized by at least one of the following: high mobil-
ity of the tooth (mobility grade III), inadequate bone support, obliteration of the root
canal, a pathological lesion extending to the successor’s tooth germ, evidence of
extensive internal/external pathological root resorption, or less than two-thirds of the
root intact [24]. Pulpectomy is a viable long-term treatment for non-vital primary
teeth without root resorption but is less successful for those with root resorption.

14.7 Pulpectomy Procedures

Clinicians may choose either a single-visit or two-visit pulpectomy based on clini-

cal expertise and individual circumstances [26, 29]. We describe here a single-visit
procedure [30].

14.7.1 Access and Debridement

Under local anesthesia and rubber dam isolation, caries is removed, and the pulp
chamber is accessed. The use of a rubber dam for non-vital procedures is accepted
as the standard of care as it is important to maintain isolation from saliva, blood, and
other contaminants [29]. Figure 14.5 demonstrates mandibular first and second

Fig. 14.5 Mandibular first and second primary molars opened for pulpectomy, showing the ori-
fices of the canals
14 Non-Vital Pulp Therapies in Primary Teeth 231

primary molars opened for pulpectomy, showing the orifices of the canals. The most
common cause of inaccessibility of primary teeth to pulpectomy is unsuitable
entrance cavity. It is followed by tortuous canals and orifice calcification. Maxillary
first molar (Fig. 14.1) is the most frequently reported as inaccessible. The least fre-
quently reported is the mandibular second molar (Fig. 14.4). The distobuccal canal
of the maxillary first molar and the mesiolingual canal of the mandibular first molar
are the most frequently inaccessible canals [15].
After the pulp, inflamed or necrotic, is removed, access preparation is refined to
make sure that entrance to all the canals is possible and clearly visible. When each
canal orifice has been located, a properly sized barbed broach used to extirpate the
pulp tissue is selected. The broach is used gently to remove as much organic mate-
rial as possible from each canal. Endodontic files are selected and adjusted to stop
1–2 mm short of the radiographic apex, with the preliminary working length esti-
mated according to the preoperative radiograph [31] and/or to the apex locator [14].
Clinicians may choose any of the methods (tactile, radiographs, apex locators)
based on their clinical expertise and individual circumstances [26]. The instruments
should be slightly bent to adjust to the curvature of the canals, thus preventing per-
forations on the outer and inner portions of the root [32]. It is important to keep in
mind that primary molar roots are usually curved to allow for the development of
the succedaneous tooth. During instrumentation, these curves increase the chance of
perforation of the apical portion of the root or the coronal one-third of the canal into
the furcation [32].

14.7.1.1 Instrumentation Technique

The main goal of canal instrumentation is the removal of organic debris [33].
Mechanical clearing of remnants from the canal is performed with a series of 21 mm
long K-type endodontic files (Unitek Corp., Monrovia, CA) up to file No. 30 or 35.
It is imperative to avoid access shaping of the canal that might lead to perforation in
the furcation or the lateral walls.
Some dentists prefer to use nickel titanium files placed in a special rotary hand-
piece for root canal debridement. This facilitates root canal instrumentation, espe-
cially in canals that are difficult to negotiate with hand instruments. Cautious
manipulation is important, however, to prevent breaking the file or over-­instrumenting
the canal and apical tissues. Rotary instrumentation decreases instrumentation time
[29, 34–36], extent of dentine removal [34], and postoperative pain (due to the
lesser amount of periapically extruded debris which triggers inflammatory process)
[36] and tends to result in more flush fills [29].
Several comparisons of instrumentation techniques showed that manual instru-
mentation with K files resulted in significantly more dentine removal when com-
pared to rotary instrumentation [1, 34], but a recent, cone-beam computed
tomography-based in vitro analysis of primary root canals found no significant dif-
ferences between rotary and manual files. Yet, the researchers concluded that the
rotary files showed better performance, as a significant difference was found at the
middle level of the root and attributed this finding to the difference in the file design
itself [37].
232 M. Moskovitz and N. Tickotsky

A meta-analysis on optimal or flush filling to the root’s apex of primary tooth

root canals in vivo showed no statistical difference but favored rotary files achiev-
ing more flush apical fills [29, 33]. Overall, the use of rotary instruments yielded
32% more flush fills than those using manual filing [29].
Intracanal separation (breakage) of nickel-titanium rotary instruments is still a
major concern of endodontists, with a consequent possible reduction in the outcome
rate [38].
In summary, the preparation of canals with rotary files can be an alternative to
conventional files in primary teeth. Rotary instrumentation time was significantly
shorter than manual by approximately 2 min, but the two instrumentation methods
had comparable successes while the occurrence of flush fills favored rotary.
Considering these findings and the additional resources/training for rotary over man-
ual instrumentation, clinicians may choose either method of instrumentation [26].
Er,Cr:YSGG laser provided similar cleanliness as rotary instrumentation tech-
nique and was superior to manual instrumentation [39]. The laser technique required
less time for completion of the cleaning and shaping procedures when compared
with both rotary and hand instrumentation [39]. One should be cautious not to use
laser technique when the patient is on inhalation sedation as it is prohibited by the
manufacturer due to the risk of sparks from the laser machine in proximity to oxy-
gen from the nitrous oxide.

14.7.2 Root Canals Irrigation

Regardless of the filing system used, non-instrumented areas still exist [35]; The
complex internal anatomy of primary molars results in zones that are inaccessible to
debridement, such as accessory canals, ramifications, and dentinal tubules [40].
While such zones are missed by instrumentation, irrigating solutions synergize
mechanical debridement by dissolving tissue and disinfecting the root canal system
and are crucial for lubrication and flushing away of necrotic and contaminated
materials [41–44]. Clinically effective and biocompatible irrigants can significantly
reduce (or even eradicate) the microorganisms and their by-products in the pulp
canals [40, 44]. Currently, there is no agreement on the best intracanal irrigant solu-
tion for use against pulp pathogens involved in irreversibly inflamed/infected or
non-vital primary teeth [40].
An ideal irrigant must have a broad antimicrobial spectrum and high efficacy
against anaerobic and facultative microorganisms, be able to dissolve necrotic pulp-­
tissue remnants, inactivate endotoxins, either prevent the formation or dissolve the
smear layer during instrumentation, and be non-toxic (to periodontal tissues), non-­
caustic, and non- allergenic [43, 44].
A major concern in root canal treatment of primary teeth is the proximity of the
permanent tooth germs, which might be affected if the cleanser material is extruded
beyond the physiologically resorbing apex [43]. An in vitro study showed that
14 Non-Vital Pulp Therapies in Primary Teeth 233

irrigant was extruded apically in teeth with open apices by both syringe and endo-
sonic methods. There was no significant extrusion of irrigant in teeth with closed
apices [45].
Clinicians are especially cautioned in the use of sodium hypochlorite (NaOCl)
for irrigation, as significant morbidity has been reported when this irrigant is
extruded past the apices of primary teeth [46–48]. NaOCl is a weak alkaline/base
that acts on the remains of pulpal tissue, food, and microorganisms, denaturing and
dissolving them in water. It is best known for its strong and rapid antibacterial activ-
ity even at low concentrations. NaOCl at 0.5–1% is recommended for use in canal
irrigation instead of the 5.25% solution [26, 43]. Er:YAG laser use with NaOCl
decreased E. faecalis slightly more than NaOCL alone [49].
Other intracanal irrigants have been proposed for primary teeth, such as
chlorhexidine gluconate, ethylenediaminetetraacetic acid (EDTA), and citric acid.
Chelating agents can be used in conjunction with irrigants: EDTA is an agent used
for the removal of the inorganic portion of the smear layer that has little if any
antibacterial activity [50]. Citric acid 6% and EDTA can effectively remove the
smear layer created during canal instrumentation [51, 52]. Pulpectomy outcome
was improved by smear layer removal using 2.5% sodium hypochlorite (NaOCl)
and 6% citric acid [51], but there is controversy whether removal of the smear
layer improves pulpectomy results [51, 52]. BioPure MTAD Antibacterial Root
Canal Cleanser (a mixture of tetracycline isomer, acid, and detergent, Biopure,
Tulsa Dentsply, Tulsa OK, USA) is a final irrigant for smear layer removal recom-
mended for use with patients over the age of 8 years. It has been proved to be
effective in eliminating resistant microorganisms and providing sustained antimi-
crobial activity [53].
Hydrogen peroxide solution was used for many years as an endodontic irrigant.
It is active against viruses, bacteria, yeasts, and even bacterial spores, but there is no
evidence supporting its use as an endodontic irrigant [40, 43].
Chlorhexidine (CHX) gluconate has a wide antimicrobial spectrum and is effec-
tive against Gram-positive and Gram-negative bacteria and yeasts. It absorbs onto
the cell wall of the microorganisms and causes leakage of the intracellular compo-
nents. At high concentrations, chlorhexidine gluconate has a bactericidal effect due
to the precipitation and/or coagulation of the cellular cytoplasm. When used in iden-
tical concentrations, NaOCl and CHX had a similar antibacterial effect in the root
canal and infected dentine, but CHX lacks the tissue-dissolving ability [43].
In recent years, the risk of allergy to chlorhexidine is increasingly recognized
[54], yet it has not been described in pulpectomy procedures.
Systematic reviews showed no impact of irrigants—sodium hypochlorite one to
5%, water/saline, or chlorhexidine—on pulpectomy success [25, 26]. Therefore,
clinicians may choose any of these irrigation solutions based on their clinical exper-
tise and individual circumstances [26].
It is recommended to irrigate with normal saline prior to drying the canals with
appropriately sized sterile paper points.
234 M. Moskovitz and N. Tickotsky

14.7.3 Filling the Root Canal(s)

An ideal root canal filling material should resorb concurrently with the physiologic
resorption of the roots and be nontoxic to the periapical tissues and the permanent
tooth bud. It should resorb readily if forced beyond the apex and be antiseptic, easy
to insert, non-shrinkable, and easily removed if necessary [55]. In addition, it should
be easily placed, not set to a hard mass that could deflect an erupting permanent
tooth [52], be radiopaque and not discolor the tooth, adhere to the walls, and not
shrink [56].
Most root filling materials for primary teeth contain resorbable materials, such as
calcium hydroxide (CH), non-reinforced zinc oxide eugenol (ZOE) [57, 58], and
iodoform. We discuss here the main characteristics of several popular materials and
focus on their mode of action and biocompatibility.
Except in anterior primary teeth, CH is always used in combination with another
filling material, such as iodoform or ZOE [59–61]. Several root canal filling materi-
als combine iodoform and calcium hydroxide [62]. Calcium hydroxide provides a
high pH (>10) environment that, along with iodoform, creates an increased bacte-
riostatic effect [61]. Vitapex™(Neo Dental International Inc., Burnaby, British
Columbia) and Metapex™(Meta Biomed LTD, South Korea) are both in a premixed
syringe, contain mostly iodoform and CH (see Table 14.1 for details), and are radi-
opaque. Both are resorbable and hence preferable in primary teeth. When extruded
into furcal or apical areas (Fig. 14.6 shows such extrusion in a mandibular left sec-
ond primary molar with four canals), they can either diffuse or be quickly resorbed
by macrophages and do not cause a foreign body reaction. Figure 14.7 shows pulp-
ectomy using Metapex in the maxillary first left primary molar demonstrating three
canals filled loosely with the material.

Table 14.1 A description of various root sealers for primary teeth

Calcium
hydroxide
Calcium (for anterior Zinc oxide
Root filling hydroxide with primary Zinc and
material iodoform teeth) oxide-eugenol Iodoform-based iodoform
Materials Vitapex™ (Neo Sealapex™ Pulpodent™ Metapex™ (Meta Maisto
Dental (Kerr, Brea, (VladMiVa, Biomed Co., paste™
International Inc., CA, USA) Bucaramanga, Ltd. Cheongju (Inodon,
Burnaby, British Calcicur™ Colombia) City, Korea) Porto
Columbia) (VOCO, Kri paste™ Alegre,
Metapex™ (Meta Germany) (Pharmachemie Brazil)
Biomed LTD, AG, Zurich, Endoflas™
South Korea) Switzerland) (Sanlor
FS,
Columbia
South
America)
14 Non-Vital Pulp Therapies in Primary Teeth 235

Table 14.1 (continued)

Calcium
hydroxide
Calcium (for anterior Zinc oxide
Root filling hydroxide with primary Zinc and
material iodoform teeth) oxide-eugenol Iodoform-based iodoform
Introduction Disposable tips or Spiral Without setting Sterile syringe Spiral
into the root spiral lentulo lentulo or accelerators with disposable lentulo
canal mounted on a auto mix may be pushed plastic needles mounted
slow speed syringes or into the root on a slow
handpiece application canals using a speed
cannula root canal handpiece
plugger
Problems Aqueous vehicles Tends to resorb Minimal
cause depletion of at a slower rate antibacterial
paste from root than the roots activity against
canals before time of the most pure
of physiological deciduous teeth cultures [68]
tooth replacement [65–67] Overfilling and
[63]. Viscous voids [69]
vehicles promote
lower solubility of
the paste. Oily
vehicles have
lowest solubility
and diffusion of
calcium hydroxide
pastes [64]
Anti-­ No antibacterial Strong Kri paste
bacterial activity against antibacterial showed stronger
activity most pure cultures effectiveness antibacterial
[70] [70, 71] effectiveness
than ZOE [71]

Fig. 14.6 Pulpectomy

using Metapex in the
mandibular second left
primary molar
demonstrating four canals
filled loosely with the
filing material extending
slightly beyond the apex
236 M. Moskovitz and N. Tickotsky

Fig. 14.7 Pulpectomy

using Metapex in the
maxillary first left primary
molar demonstrating three
canals filled loosely with
the material

CH pastes (Calcicur™, by Voco America Inc., USA; Apexit Plus™by Ivoclar

Vivadent AG, Schaan, Liechtenstein; and Sealapex™ by Kerr Corp., USA) for ante-
rior teeth pulpectomies can be used either in premixed syringes or mixed as a pow-
der and water. Contrary to CH that does not cause discoloration, iodoform-containing
filling materials may cause discoloration in the coronal part of the teeth [72] espe-
cially when used in anterior primary teeth.
Non-reinforced zinc oxide-eugenol (ZOE) is another popular root canal filling
material. For primary teeth pulpectomy, zinc oxide powder is mixed with eugenol to
a creamy or thick consistency which is radiopaque. In teeth with irreversible pulpal
changes pulpectomies with ZOE or Endoflas™(Endoflas™ contains ZO/iodoform/
CH, i.e., ZOE plus iodoform plus calcium hydroxide) gave similar outcomes to
Vitapex™ and Sealapex™, although there was no agreement with regard to filling
materials’ resorption [73]. Overfilling and voids were more commonly seen in teeth
filled with Metapex™ [69]. There was no significant difference between Endoflas™,
Metapex™, and ZOE in pulpectomy success rates. The decreased use of ZOE nowa-
days may reflect the concern that it is non-resorbable and may prevent timely root
resorption of the exfoliating tooth. In addition, extruded ZOE might cause a foreign
body reaction [61].
Iodoform-based paste, KRI paste™, demonstrated higher success rates (84%)
than ZOE (65 %) [61, 74]. ZO/iodoform/CH or ZOE maintained an 18-month suc-
cess rate approximating 90% over time while iodoform success decreased to 71% or
lower over time [26, 29]. Using iodoform-based filling material for pulpectomy of
primary teeth, like the one used in Brazil known as the Guedes-Pinto™ (GP) paste
composed of iodoform, camphorated paramonochlorophenol (PMCC), and a der-
matological ointment containing prednisolone acetate and rifamycin [75], is not
well supported in the literature.
14 Non-Vital Pulp Therapies in Primary Teeth 237

Based on these findings, Ca(OH)2/iodoform is recommended for pulpectomy in

primary teeth nearing exfoliation while ZOE-containing pastes should be utilized
when exfoliation is not expected to occur soon [76].
The evidence suggests that ZO/iodoform/CH and ZOE may be a better choice for
pulpectomy success compared to iodoform at 18 months. Meta-analysis after
18 months showed that ZO/iodoform/CH ranked first followed by ZOE and then
iodoform [26].
Chairside mixed materials are more time-consuming and technique-sensitive
than those that come in a syringe. Also, the material must be carried into the canal
with a lentulo or rotary instrument that may break inside the root canal, especially
in primary teeth with tortuous root canals. In case of a broken instrument in the
canal, one should consider extracting the tooth or performing a close follow-up and
extracting the tooth as soon as the tooth bud is approaching the edge of the lentulo
revealed by the resorbing root.
The instruments that are used to fill the canals vary according to the type of fill-
ing material. Thick pastes such as ZOE are inserted and condensed with root canal
pluggers, while diluted pastes like iodoform and calcium hydroxide-based materials
are inserted with a spiral lentulo mounted on a slow speed engine. Other materials
are inserted by plastic syringes and tips provided by the manufacturer. A final X-ray
is necessary to evaluate the filling of the canals and ensure no overfilling that might
damage the permanent tooth germ [24].
The quality of the root canal fill (flush fill—a canal filled to the apex) and pulp-
ectomy success using lentulo spirals, hand pluggers, and syringes were not statisti-
cally different [29]. Two studies comparing different methods for filling the canals
showed differing results. Using a spiral lentulo resulted in 63–91% flush fills versus
48–87% with a hand plugger and 62–87% with a syringe. In both studies, there was
no significant difference (P = 0.13, P = 0.66) between the three methods of obtura-
tion in achieving pulpectomy flush fills [25, 29, 77].
Overfilling of the canals appears to be related to a lower success for pulpectomy
[29]. Some techniques may cause more overfills (lentulo spiral) than others [25, 26,
77]. Metapex fillings showed more overfilling and voids than Endoflas and ZOE [24].

14.8 Supplementary Methods

Dental operating microscopes, electronic apex locators, rotary nickel-titanium files,

and irrigation techniques are at the front of the endodontic armamentarium today
[14, 31, 78].
The use of a dental operating microscope is not essential when treating primary
teeth [14], as contrary to permanent teeth, preparation of root canals in primary
teeth is based on chemical means rather than on mechanical debridement [31].
238 M. Moskovitz and N. Tickotsky

14.8.1 Electronic Apex Locators

Besides their essential role in preoperative evaluation, radiographs are the most
prevalent method for measuring the working length in primary teeth [14]. Electronic
apex locators can serve as an adjunct means to overcome the two-dimensional limi-
tations of the radiographic image and reduce both radiation exposure and process-
ing time, making the treatment more convenient to both the operator and the child.
They can also help detect root perforations resulting from internal or external root
resorption [14]. There is controversy if the use of apex locators is superior to the
radiographic method [79–81], as no statistically significant differences were found
between radiographic image and apex locator lengths [82].
While early research claimed that the physiological resorption in primary teeth
compensates apex locators’ performance [83], limiting them for use only as an addi-
tion to other diagnostic measures [63], more recent studies have shown that they can
give accurate results in primary teeth [26, 84]. The presence of root resorption did
not affect the accuracy of the measurement [85].
Specifically, Root ZX™ mini apex locator showed the most promising results,
followed by digital radiography and conventional radiography [84].

14.8.2 Ultrasonic Instrumentation

Ultrasonic appliances produce high-frequency vibrations of over 30,000 Hz, which

provide better cleaning and smear layer removal inside the canals [86, 87]. The use
of K-type files with the ultrasonic technique does not eliminate the need for conven-
tional hand instrumentation [87], so the technique combines manual root canal
preparation with sodium hypochlorite 1% or 3% irrigant and K-type files. When the
working length is determined, the same file size (usually 15) is used with the ultra-
sonic technique to enlarge the canals under constant irrigation [43, 86, 87]. The use
of ultrasonic instrumentation in primary molars reduced appointment time and
showed a high success rate [87] of 97.5%, with a mean follow-up time of 19.9 months
[86]. No significant difference in radiographic healing of apical periodontitis was
found between ultrasonic and syringe irrigation [88].

14.8.3 Lesion Sterilization Tissue Repair (LSTR)

A new biologic approach in the treatment of carious lesions with or without pulpal
and periapical involvement developed at the Cariology Research Unit of the Niigata
University, School of Dentistry in Japan, advocates the concept of “no instrumenta-
tion endodontic treatment” (NIET). It is also called “lesion sterilization and tissue
repair” (LSTR). LSTR procedure for necrotic primary teeth usually requires no
instrumentation or filling of the root canals. Instead, an antibiotic mixture is placed
in the pulp chamber to disinfect the root canals [25, 26]. For teeth without
14 Non-Vital Pulp Therapies in Primary Teeth 239

preoperative root resorption pulpectomy was more successful than LSTR, indicat-
ing it should be preferred over LSTR in these teeth [26].
LSTR procedure: After opening the pulpal chamber of a necrotic tooth, the
canal orifices are enlarged using a large round bur to create medication holder. The
walls of the chamber are cleaned with phosphoric acid and then rinsed and dried
[89]. The 3 Mix-MP [90], an antibiotic mixture of clindamycin, metronidazole, and
ciprofloxacin, from crushed tablets, is mixed with a liquid consisting of polyethyl-
ene glycol and macrogol to form a paste placed directly into the medication recep-
tacles and over the pulpal floor [89]. It is then covered with a glass-ionomer cement
and restored with a stainless steel crown [89]. Following treatment, pretreatment
clinical signs and symptoms should resolve, and the radiographic picture of the
lesion should show the repair.
The antibiotic mixture targets both aerobic and anaerobic bacteria and sterilizes
infected necrotic pulp and root dentine [91, 92]. Similar success rates have been
reported for minocycline and clindamycin [93], while tetracycline reduces the suc-
cess of the mixture [25]. Therefore, the AAPD’s practices on the use of non-vital
pulp therapies in primary teeth recommend that antibiotic mixtures used in LSTR
should not include tetracycline/minocycline and that clinicians replace it with
another antibiotic such as clindamycin [26]. Clinicians must consider the fact that
the efficacy of antimicrobial filling pastes containing antibiotics decreases over time
due to the high prevalence of resistant bacteria in the root canals [94].
The clinician’s choice between pulpectomy and LSTR should be based on the
following considerations: rate of root resorption, time to exfoliation, and strategic
tooth position in the arch. LSTR can be considered effective for teeth with advanced
root resorption when conventional endodontic treatment is contraindicated [91].
For teeth without preoperative root resorption, pulpectomy showed higher suc-
cess rates than LSTR [95, 96]. Based on 12-month results, pulpectomy is preferred
over lesion sterilization tissue repair in non-vital teeth with no root resorption.
LSTR is preferred over pulpectomy in non-vital teeth with root resorption when a
tooth needs to be maintained in the arch for 12 months or less [29].
LSTR-treated teeth did not resorb, unlike untreated contralateral teeth [97]. This
treatment adversely affected the permanent tooth eruption due to interradicular
bone loss surrounding the crown and, in one case, caused an odontogenic kerato-
cyst [97].

14.9 Evaluation of Pulpectomy

Failure of a pulp treatment is manifested by at least one of the following outcomes:

soft tissue pathology, pain, pathologic mobility, pathologic radiolucency, and/or
pathologic root resorption [28].
Pulpectomy is considered successful if pre-treatment clinical signs and symp-
toms resolve within a few weeks. The treated tooth should be painless, with no
increased mobility, no sensitivity to percussion, and healthy surrounding soft
240 M. Moskovitz and N. Tickotsky

tissues. Radiographically, there should be evidence of successful root canal filling

without gross overextension [24, 58–60]. The treatment must allow concurrent
resorption of the primary tooth root and filling material to permit normal eruption of
the succedaneous tooth.
Radiographic findings of lesions pre-treatment should resolve within 6 months,
with evidence of bone deposition and a decrease or disappearance [66, 96] or at
least no increase in the size of prior radiolucent areas. A static or unchanged radio-
lucency means the infection is still present but not causing clinical symptoms.
Preoperative periradicular radiolucency decreases treatment success and tooth sur-
vival following pulpectomy [98, 99].
Cases where pre-existing radiolucent defects have grown or new defects appeared
are considered a failure of treatment. No pathologic root resorption, furcation/apical
radiolucency [60, 100], or new lesion should appear after treatment.
Clinicians should evaluate non-vital pulp treatments for success and adverse
events clinically and radiographically at least every 12 months.
Success rates of root canal treatments in primary teeth have been extensively
discussed in the literature, with pulpectomies being generally more successful
than pulpotomies [24]. For non-vital teeth, pulpectomy is recommended for long-
term success (greater than 24 months) in teeth when there is no root resorption
present.
Pulpectomies success varied according to the root canal filling material used and
evaluation type (clinical or radiographic): in clinical trials, ZOE had 82–100% suc-
cess, calcium hydroxide with iodoform pastes had 80–100% success, and iodoform
pastes had 93.3–100%. In radiographic examinations, ZOE had 65–100% success
[55, 60, 64, 66, 74, 96, 100], calcium hydroxide had 72.5–100%, and iodoform
pastes had 72.5–90.3% success [24]. A review of clinical and radiographic follow-­
ups up to 24 months did not find sufficient evidence to establish the superiority of
one medicament over another regarding clinical failure [101].
Another factor of pulpectomy success is the follow-up period. For long-term suc-
cess (greater than 18 months), ZOE/iodoform/calcium hydroxide or ZOE fillers per-
form better than iodoform fillers [29]. Endoflas and zinc oxide eugenol showed
93.3% success, whereas a higher percentage of success was observed with Metapex
(100%) [69].
ZOE with iodoform, calcium hydroxide with iodoform, and ZOE were found to
have more than 90% success rate and were all equally effective at 30 months [56].
Restoration time: Data of 24-month follow-up suggests that teeth restored with
stainless steel crowns had better success than composites (90% vs. 77%). Success
rates for 1 year posttreatment did not differ between restorations placed on the same
appointment as the pulpectomy and restorations placed at the next appointment
(82% compared to 83%) [26].
Obturation method, number of treatment visits, method of root length determina-
tion, irrigation solutions, smear layer removal, timing/type of the final restoration,
and type of tooth treated (molar versus incisor) do not impact the success rate of
pulpectomies [29].
14 Non-Vital Pulp Therapies in Primary Teeth 241

14.10 Adverse Effects of Pulpectomy

Little is known about the consequences of primary teeth pulpectomy on the devel-
opment of permanent tooth buds and the eruption of the permanent teeth.
The type of root canal filling material, preoperative periapical radiolucency, and
inadequate treatments have been shown to influence pulpectomy adverse effects.
Type of root canal filling material: ZOE filling material has a 20% chance of
altering the path of permanent tooth eruption [57]. ZOE tends to resorb more slowly
than the root of the primary tooth and may be retained after pulpectomized tooth
exfoliation. Remnants of ZOE were found in the alveolar bone of up to 70% of
exfoliated primary teeth, and the material was still retained in more than a quarter
of the patients 3 years posttreatment [102, 103]. Retained ZOE may deflect the per-
manent tooth’s path of eruption [52].
In the case of traumatized incisors that had a pulpectomy, ectopic eruption of a
permanent incisor might also be due to the trauma to the primary incisor affecting
and/or dislodging the developing permanent bud. Incisor pulpectomy success rates
do not appear to be much different if treated due to trauma or caries after
12 months [29].
Contrary to ZOE, iodoform fillers resorb at a faster rate than the root, resulting
in the pulpectomy filling looking more like a pulpotomy after 12 to 18 months [57,
99, 102]. Also, iodoform-containing root canal filling was found to accelerate root
resorption [104].
Leakage of root canal filling material from resorbed primary apices might lead to
low-grade irritation to the dental sac of the permanent successor and to development
of radicular cysts around the permanent tooth buds [99, 105]. Enlargement of the
dental sac in association with a root treated primary tooth occurred in 3.3% of the
followed cases, but the development of a true radicular or dentigerous cysts was
rare. Despite the low occurrence, dentists should be aware of this phenomenon and
radiographically monitor root canal treated teeth until shedding [105]. Most radicu-
lar cysts in the primary dentition do not demonstrate clinical signs, but cysts of a
certain size might displace the developing tooth bud [16, 57, 106, 107] and expand
the buccal cortical plate [16, 107].
Although rare, hypoplasia in the permanent successor as a sequela to a pulpec-
tomy in a primary tooth may occur even after a successful pulpectomy [99, 108].
Incorrectly performed root canal treatments may stop the eruption of the suc-
cedaneous teeth [109]. Canal overfilling may cause a mild foreign-body reaction
and an increased failure rate when compared to underfilling or flush finishing [74].

14.11 Adjunctive Systemic Antibiotic Treatment

Dentists prescribe approximately 10% of antibiotics dispensed in primary care and

so contribute to the development of antibiotic-resistant bacteria [110]. In root canal
treatments, the lack of blood circulation in the root canal prevents antibiotics from
242 M. Moskovitz and N. Tickotsky

reaching the area and renders them ineffective in eliminating the microorganisms
[111]. The American Association of Endodontics guidelines [112] stress that the
most important step in the treatment is dental management of the condition or refer-
ral for endodontic management of the patient. Systemic antibiotic treatment in con-
junction with endodontic therapy is indicated in the following cases:

1. Acute apical abscess in medically compromised patients.

2. Acute apical abscess with systemic involvement, e.g., localized fluctuant swell-
ings, elevated body temperature, malaise, lymphadenopathy, and trismus.
3. Progressive infections (rapid onset of severe infection over less than 24 h, cel-
lulitis or spreading infection, osteomyelitis).
4. A systemic antibiotic is not indicated in the following:
(a) Symptomatic irreversible pulpitis (pain, with no other symptoms and signs
of infection).
(b) Pulp necrosis.
(c) Symptomatic apical periodontitis (pain, pain to percussion and biting and
widening of periodontal ligament space).
(d) Chronic apical abscess (teeth with sinus tract and periapical radiolucency).
(e) Acute apical abscess without systemic involvement [113].

Antibiotics should be prescribed only when genuinely needed and only as an

adjunct to, not an alternative to, other interventions (e.g., pulp therapy or extraction)
to control the infection source [114].
Amoxicillin is the drug of choice for dental infections in non-allergic children. It
has been shown to be effective against oral flora; is well absorbed from the gastro-
intestinal tract; provides high, sustained serum concentrations; and has a low inci-
dence of adverse effects [114]. Moderate to severe pain 24 h post a pulpectomy
procedure is rare [29], and it is important to note that antibiotics do not affect pain
associated with dentoalveolar infection [115]. The use of antibiotics before end-
odontic treatment of asymptomatic non-vital teeth has no effect on the flare-up
rate [115].
The traditional minimal duration of a drug regimen is 5 days beyond the point of
substantial improvement. Patients’ compliance with the treatment can be improved
by prescribing medications that can be given once or twice daily rather than three
times a day. For odontogenic infections with non-localized and progressive swelling
and systemic manifestations (e.g., fever, difficulty breathing or swallowing), imme-
diate surgical intervention and medical management with intravenous antibiotic
therapy expedite the cure.

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Sealing and Building Up the Pulp
Chamber and Crown with Glass Ionomer 15
and Other Materials After Pulp Therapy

Joel H. Berg

Contents
15.1 Introduction 249
15.2 Premise and Conceptual Framework 250
15.3 Boundaries of This Chapter Conversation 251
15.4 Purpose of Fill/Goals 251
15.5 Sealing the Orifices 252
15.6 Material Choices for Pulp Chamber Fill 252
15.6.1 Zinc Oxide: Eugenol 252
15.6.2 GIC Materials 253
15.6.3 Composite 254
15.7 Assessment/Outcomes 255
References 255

15.1 Introduction

This chapter will discuss the ever-important component of pulp therapy that includes
the filling of the pulp chamber after completion of the pulp therapy per se and prior
to the external restoration of the tooth. Although this content is discussed discreetly,
it overlaps with other topics discussed in other chapters in this book. The materials
that will be discussed in this chapter as well as the techniques of using those materi-
als may also be discussed in the context of other aspects/chapters of this book, yet
herewith we will discuss the specific use of these materials and techniques for the
purpose of pulp chamber filling.

J. H. Berg (*)
University of Washington School of Dentistry, Glendale, AZ, USA
e-mail: [email protected]

© The Author(s), under exclusive license to Springer Nature Switzerland AG 2023 249
A. B. Fuks et al. (eds.), Contemporary Endodontics for Children and
Adolescents, https://doi.org/10.1007/978-3-031-23980-9_15
250 J. H. Berg

15.2 Premise and Conceptual Framework

When one considers the various aspects of pulp therapy for children, filling of the
pulp chamber is a very small component. However, structurally and from the per-
spective of sealing is an extremely important part of the overall process. Therefore,
although this chapter is shorter in length than many of the other chapters in this
book, it provides connectivity to the other components of the pulp therapy process
from the just completed pulp therapy below, as well as sealing the tooth structure so
that the restorative material placed above the pulp chamber fill is intact and pro-
tected against further destruction.
In terms of structural integrity of the tooth, one can imagine that by removing
tooth structure to gain access to the pulp as part of the pulp therapy process, there
may be enough destruction/removal of tooth structure to allow degradation of the
quality of the strength of the crown of the tooth regardless of subsequent restoration.
For permanent teeth, and for crowns or other, the crown buildup procedure is a com-
mon part of the process. In fact, it is deemed to be a separate procedure with its own
procedure code and own billing components. Generally speaking, most crowns for
permanent teeth regardless of how they are restored are preceded by the placement
of a so-called crown buildup procedure. This procedure discussed over many
decades has evolved into what results in the preparation of the tooth prior to receiv-
ing the external restoration. In other words, for permanent teeth, after the buildup,
the final restoration of the tooth structure can be placed so that it can receive an
extracoronal restoration such as a full crown [1–4].
In the case of primary teeth which have received pulp therapy, the situation is a
little bit different. First, the volume of tooth structure removed to gain access
through the pulp chamber into the pulp area where the procedure is performed is
much smaller [5]. Therefore, the relative strength loss in terms of structural integrity
of the tooth is reduced significantly from what it would be in a permanent tooth [6,
7]. Even though there may be a high percentage of volume removed to gain access
to the pulp in order to perform the pulp therapy in the case of a primary molar, it is
adequate to preserve the original strength of the tooth and to ultimately receive a
restoration above, be it in intracoronal or extracoronal [8–12].
Regarding sealing, let us first discuss sealing above the orifices that have been
previously sealed as part of the pulp therapy procedure. For purposes of our discus-
sion in this chapter, we will assume that the pulp therapy has been completed per
instructions as discussed in other chapters. For example, the pulp therapy was com-
pleted with removal of the vital or nonvital tooth structure, cleaning and drying, and
filling of the pulp chamber where the pulp resided previously; the orifices must have
been sealed at the conclusion of that procedure. This usually takes place together
with the component of the procedure we are now discussing. We will discuss them
as discrete procedures. Therefore, I will not go into detail on the pulp therapy per se
as discussed in detail in many other chapters but will discuss solely the filling
between the sealing of the pulpal orifices and the external restoration of the tooth.
With the assumption that the pulp therapy is completed, and the orifices have been
sealed with mineral trioxide aggregate (MTA), we now must guarantee that the seal
15 Sealing and Building Up the Pulp Chamber and Crown with Glass Ionomer… 251

is continued into the pulp chamber and then externally to the restoration which is
placed above the pulp chamber fill [13–18].
This is easily achieved with a variety of materials. We will discuss a few of them
in this chapter and why those materials are the correct materials to be used in this
circumstance, that is, filling of the pulp chamber itself. Our definition of pulp cham-
ber for purposes of this component of the procedure is that component of the tooth
structure was removed to eliminate decay or to gain access to the pulp itself in order
to perform the pulp therapy procedure.

15.3 Boundaries of This Chapter Conversation

After pulp therapy and sealing the orifices (this chapter will discuss the proper
methods of guaranteeing a seal over the orifices, as well as the proper choice of
material), the actual build-up of the pulp chamber cavity to fill the chamber created
by removing decayed tooth structure or healthy tooth structure in order to access the
pulp for the pulp therapy procedure must be completed.
As an extrapolation from the science of permanent tooth root canal therapy,
Gillen et al. [19] performed a critical systematic review examining the factors
important to the successful outcome of RCT in permanent teeth. It was concluded
that more important than the method of root canal treatment or fill technique were
two elements. The seal of pulp treatment from above, the seal of the ultimate resto-
ration of the tooth [19]. “On the basis of the current best available evidence, the
odds for healing of apical periodontitis increase with both adequate root canal treat-
ment and adequate restorative treatment. Although poorer clinical outcomes may be
expected with adequate root filling-inadequate coronal restoration and inadequate
root filling-adequate coronal restoration, there is no significant difference in the
odds of healing between these two combinations” [19].
Although there is inadequate literature regarding the impact of these same fac-
tors on the success of primary tooth pulp therapy with the same level of evidence,
there is reason to believe from the existing literature, as discussed on other chapters
of this textbook that the same biological principles apply [20–28].

15.4 Purpose of Fill/Goals

The restoration of choice for primary molars following pulpotomy has traditionally
been the stainless-steel crown; this extracoronal restoration requires the removal of
tooth structure beyond that affected by the decay and the pulpotomy procedure.
Although this chapter will not discuss the ultimate restoration of the tooth after pulp
therapy, it will discuss the buildup of the core opening to access the pulp chamber
in order to perform pulp therapy.
Over the last decades, various materials have been formulated to fill the pulp
chamber after sealing the pulp orifices after completion of a pulpotomy. The most
common material has been the use of zinc oxide eugenol (ZOE), as a paste to seal
252 J. H. Berg

the orifices of the pulp chamber and also to fill the pulp chamber entirely up to the
point of the ultimate restoration whether it be a stainless-steel crown or other type
of material [29–34].
This author reported on the use of glass ionomer combined with silver material
as an ideal choice of material to fill the cavity of the pulp chamber created by access
in order to perform pulp therapy material which provides all the properties of a
traditional glass nominator with the additional strength characteristics of silver [35–
39]. Today, modern glass ionomer materials are quite useful for this purpose, as they
are strong and also yield incredible sealing characteristics, being that glass ionomer
materials are the only material which chemically bonds to structure, thereby apply-
ing a seal. Any other choice of material requires an intermediate bonding step above
pulp chamber orifices in order to provide an effective seal.

15.5 Sealing the Orifices

Mineral trioxide aggregate (MTA) has been clearly documented to be the material
of choice to seal the orifices and to complete a primary molar pulpotomy procedure.
In a search of the literature over nearly 20 years of work, Musale et al. showed that
the use of MTA as a sealing agent during and after primary tooth pulpotomy was
evaluated to be extremely successful. “MTA pulpotomy has been a successful treat-
ment modality in primary molars with proven success over the years” [28]. The
procedure for performing a pulpotomy using MTA as the pulp orifice sealing agent
during and after the completion of the pulp therapy itself is discussed in other com-
ponents of this textbook.
Having completed the pulp therapy using MTA, it is now important to direct our
attention to providing “contiguity of seal” within and above the orifices of the now
sealed pulp therapy. This provision of seal integrity is provided by the use of appro-
priate materials for filling the access area created by performing the pulp therapy
procedure [40–46].

15.6 Material Choices for Pulp Chamber Fill

15.6.1 Zinc Oxide: Eugenol

Historically, a variety of materials have been used to fill the pulp chamber after a
pulpotomy procedure. Namely, zinc oxide eugenol (ZOE) combination cement
materials have been employed with great prevalence of use. Although these materi-
als provide some kind of interface and meet the objectives of filling the pulp cham-
ber access area, they are not ideal for creating a contiguity of seal and similarly are
not ideal for providing structural strength for the tooth. Therefore, it is not recom-
mended to use ZOE for this purpose [47, 48].
15 Sealing and Building Up the Pulp Chamber and Crown with Glass Ionomer… 253

15.6.2 GIC Materials

Glass ionomer has been shown to be a useful and nearly ideal material for filling the
pulp chamber after pulp therapy in primary molars [35].
Glass ionomer cement is a salt, by chemical definition, which is formed by the
reaction between a polyalkenoic acid and an aluminum-containing glass. Aluminum,
as a constituent element in the glass, is critical for the glass ionomer reaction to
occur. Most commonly, the “base” part of the reaction is the glass. Water is a neces-
sary ingredient of glass ionomer, as an acid-base reaction can only occur in a water-­
containing medium. Fluoride is added to the glass material and is released over time
to provide additional benefit to the material. This describes a so-called traditional
glass ionomer material. Modern materials often contain resin mixed with the glass
ionomer to allow a “resin-modified” glass ionomer material to be used. Such mate-
rials are denser in composition, have improved mechanical properties offering more
significant strength, and are less brittle due to the resin additives [48, 49]. Glass
ionomer can be used as a liner, as luting cement, as a base core material, such as we
are discussing herewith, and as a restorative material. As a pulp chamber filling
material, glass ionomer acts as a restorative material to restore the pulp chamber
component of the tooth, which was destroyed during access to provide the pulp
therapy. Glass ionomer offers the advantage of being the only material used in den-
tistry with a true covalent chemical bond with tooth structure.
Therefore, (most effectively with MTA) there is a seal between the glass ionomer
and not only with the MTA material itself, but to even a greater extent with the sur-
rounding dentin and enamel that were hollowed out during the access to perform the
pulp therapy procedure. Even though the measured in vitro bond strength of glass
ionomer to tooth structure is lower than the bond strengths of other materials such
as resin composite, experience shows that glass ionomers are very well retained.
This is due to the fact that the chemical bond has a different character than the
purely mechanical bond of other materials, such as resin composite. Certainly,
within the pulp chamber, glass ionomer is particularly well suited, as the otherwise
present shear and compressive forces that might be destructive to a restoration made
of this material are not exhibited or manifested within the pulp chamber, which is
subsequently covered with an alternative form of ultimate restoration such as with a
stainless-steel crown or a resin composite material above.
As mentioned, physical properties of traditional glass ionomers have been
improved recently with the introduction of high powder-to-liquid ratio glass iono-
mer materials. These denser materials, although not containing monomeric resin,
are stronger and provide a “condensable” feel, facilitating placement into pulp
chambers. These strong materials have improved compressive and flexural strengths,
allowing their use (without resin) to be sustainable pulp chamber filling materials
[50, 51], when used as a buildup material after primary tooth pulp therapy. Another
advantage of glass ionomer materials, compared with essentially every other mate-
rial that has been used to fill the pulp chamber, is the compatible coefficient of
thermal expansion. Glass ionomers have a coefficient of thermal expansion quite
similar to dentin. This compatibility means that as the tooth naturally expands and
254 J. H. Berg

contracts with variations in temperature during eating and drinking foods of various
temperatures. The mere continuous presence of saliva in the mouth will not subject
the glass ionomer material or the tooth to fracture as a result of incompatible expan-
sion characteristics.
Recently, in discussing the best materials for pulp chamber filling, glass iono-
mers continue to be recommended particularly to be used to fill the pulp chamber.
One potential disadvantage of course is because these materials are self-curing it
can take several minutes for them to fully harden (actually full setting might take as
long as 24 h, with the initial stability after 5–7 min). However, as part of the pulp
therapy procedure when the pulp chamber is filled in this instance with glass iono-
mer, be at resin-modified or otherwise, by the time the restoration is immediately
placed above (whether it’s a stainless crown or a resin composite), the glass ionomer
will be fully set even if it’s in its pure form, by the time the full procedure is com-
pleted. Some clinicians prefer to use resin-modified glass ionomer because of their
handling characteristics. They are less sticky, where stickiness can be the case with
traditional glass monomers.
The resin-modified glass ionomers also possess command cure characteristics.
However, the cure of the glass ionomer itself, that is, the acid-base reaction, only
takes place after several minutes and is fully set within 24 h. This further makes
either traditional glass ionomers or resin-modified glass monomers, highly suited to
the to be used as a pulp chamber filling material.

15.6.3 Composite

Composite resin, also known as resin composite, is the most esthetically desirable
material in terms of filling materials for pediatric or adult dentistry. Composite resin
contains a monomeric or pre-polymeric resin that is filled to various levels with
glass or quartz. The filler particles are silanized to allow the hydrophilic filler to
bond to the hydrophobic resin material. As a result, this resin composite material
ends up being quite hydrophobic, and there must be an intermediate bonding layer
placed to allow it to bond to the tooth structure mechanically.
Although the bond is strong as a mechanical bond, the material requires several
additional steps in the etching, priming, and bonding to obtain an acceptable bond
between the composite material and into the structure. In the instance of pulp cham-
ber filling, the advantage of resin composite is that it is quite strong for filling, an
important objective toward structural integrity of the tooth. If the ultimate restora-
tion of the tooth above is to be made with resin composite, then composite within
the chamber could be a contiguous component of the restorative material above, as
opposed to a separate component [51].
However, it can be argued that the composite in this instance is less desirable
than it might be as an intracoronal restoration. Additionally, because the coefficient
of thermal expansion of resin composite is not compatible with dentin, it is more
challenging as a pulp chamber filling agent than glass ionomer alone, which itself is
an adhesive. One must also be aware that the polymerization shrinkage of
15 Sealing and Building Up the Pulp Chamber and Crown with Glass Ionomer… 255

composite can be significant, making it less suitable than glass ionomers which do
not undergo significant polymerization shrinkage. Resin composite could shrink as
much as 2 or 3% which alone could cause fracture or leakage problems later once
the ultimate restoration is placed.
As with any clinical situation evaluating which material should be used for a
given situation must include a determination of the in situ characteristics after the
restoration is placed. Therefore, when one weighs the advantages and disadvantages
of the various materials which might be used to fill the pulp chamber after comple-
tion of pulp therapy in primary teeth, it becomes quite clear that the use of glass
ionomers is particularly suitable for this circumstance. Although we could list a
multitude of other materials that might be used to fill the pulp chamber, and indeed
many have been used over many decades, today with the expansive development of
glass ionomers as they are, it seems that this is the most suitable material to fill the
pulp chamber component. In some instances, where the orifices of the primary
molar are well covered with MTA, and there exists only a small “pulp chamber”
space below the ultimate restoration using a stainless-steel crown, perhaps in this
instance the MTA alone would be sufficient to fill the pulp chamber and an interme-
diary layer of glass ionomer might not be necessary or purposeful.

15.7 Assessment/Outcomes

Going back to what was stated throughout the chapter, it is always important to have
situational awareness. This means being attentive to the exact nature of the tooth
structure situation, what is remaining, what has been removed, and what needs to be
restored. Once this awareness is in place in the mind of the clinician, only then can
the suitable materials and methods be deployed correctly. One must situate them-
selves in the clinical circumstance present at the time and be certain that after place-
ment of all aspects of the restoration, having completed pulp therapy on a tooth,
what is best suited to sustain the tooth in the mouth in a healthy fashion, until the
natural exfoliation of the primary tooth. As it turns out, this very small aspect of the
overall treatment, the filling of the pulp chamber, is a major determinant of success
of the overall pulp therapy procedure.

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Restorative Guidelines
for Endodontically Treated Primary 16
Teeth

E. LaRee Johnson and Marcio Guelmann

Contents
16.1  Introduction 260
16.2  Beyond the Tooth… Patient Behavior, Clinical Skills, Modality of Care
Delivered, and Special Healthcare Needs 261
16.3  Isolation 263
16.4  Mouth Props and Bite Blocks 265
16.5  Amalgam Restorations 266
16.6  Composite Resin and Compomer Restorations 267
16.7  Composite Strip Crowns 269
16.8  Glass Ionomer Restorations 270
16.9  Sandwich Restorations (Glass Ionomer and Composite) 270
16.10 Stainless-Steel Crowns (SSCs) 271
16.11 Pre-veneered Stainless Steel Crowns 274
16.12 Zirconia Crowns 275
16.13 Final Tips 278
16.14 Conclusion 279
References 279

E. L. Johnson
Department of Pediatric Dentistry, University of North Carolina and East Carolina University,
Chapel Hill and Greenville, NC, USA
Carolina Pediatric Dentistry, Raleigh, NC, USA
e-mail: [email protected]
M. Guelmann (*)
Department of Pediatric Dentistry, University of Florida College of Dentistry,
Gainesville, FL, USA
e-mail: [email protected]

© The Author(s), under exclusive license to Springer Nature Switzerland AG 2023 259
A. B. Fuks et al. (eds.), Contemporary Endodontics for Children and
Adolescents, https://doi.org/10.1007/978-3-031-23980-9_16
260 E. L. Johnson and M. Guelmann

16.1 Introduction

The ideal dental restoration should replace and maintain the integrity of tooth struc-
ture and the dental arch from a growth and development perspective. It should seal
the restoration from the oral environment, decreasing the susceptibility to recurrent
lesions and infection. Material selection and quality of the restoration are para-
mount to ensure tooth and restoration longevity [1].
A variety of restorative materials are available. Once the clinician understands
materials’ properties and indications, the selection should be based on individual
needs [2]. However, multiple factors must be taken into consideration regarding the
patient and the provider: caries risk, age and behavior, remaining tooth structure,
tooth type (anterior versus posterior), longevity of the tooth, esthetics, clinical skills,
practice limitations and resources (academic, private, public health, military, corpo-
rate), and financial considerations [3].
After accurate diagnosis and treatment of the pulp, quality restorative work is
imperative for pulp treatment success. Failures may be due to non-ideal restorative
choices, poorly placed restorations, or temporary restorative treatment that never
received a definitive restoration and ultimately failed. Parents’ demand for esthetics
is a key factor in contemporary pediatric dental practice. When integrating pulp
therapy into the highest esthetic result, it is imperative to only use non-staining pulp
medicaments and avoid leaving silver diamine fluoride (SDF) as part of an indirect
pulp cap (IPC) treatment as both agents may result in dark tooth-colored restora-
tions, dark strip crowns, and dark zirconia crowns.
The periapical radiograph below (Fig. 16.1) is an example of a young child who
received two pulpotomies with mineral trioxide aggregate (MTA) on teeth K (75)
and L (74) and stainless-steel crowns. Failed treatment in this case could be attrib-
uted to poor diagnosis of the pulp treatment needed, inadequate mix of MTA in
combination with inappropriate packing of the MTA that did not make adequate
contact and failed to seal the pulp stumps. Moreover, the oversized crowns may
have led to washout of the cement and ultimately the MTA, rendering bacterial
penetration into the pulp causing abscesses. Without excellent pulpal medicament
contact with the pulp to promote healing and seal with a competent restoration, pulp
treatment will most likely be compromised.

Fig. 16.1 Symptomatic

teeth after failed MTA
pulpotomies on teeth # K
(75) and L (74) restored
with stainless-steel crowns
16 Restorative Guidelines for Endodontically Treated Primary Teeth 261

For primary anterior teeth, full coronal restorations are recommended when mul-
tiple surfaces and/or the incisal edge are involved and after pulp therapy. The options
available are resin-based bonded restorations (strip crowns), co-polyester crowns,
metal-based esthetic crowns (composite resin placed on open-faced stainless-steel
crowns, pre-veneered stainless-steel crowns), and zirconia crowns [4]. Examples,
indications, and contraindications for each of these crowns are illustrated through-
out this chapter, with the exception of co-polyester and open-faced stainless-steel
crowns, as they are no longer considered the standard of care. Posterior tooth full
coronal coverage options include stainless-steel crowns, zirconia crowns, and the
latest contempory option, high strength resin polymer crowns. In limited situations
after pulp treatment, amalgam and composite resin restorations may be considered
(Refs- Image of reference at the end of the chapter) [5]. The goal of this chapter is
to provide clinicians with guidance and options for restorative procedures on end-
odontically treated primary teeth considering the aforementioned factors.

16.2 Beyond the Tooth… Patient Behavior, Clinical Skills,

Modality of Care Delivered, and Special
Healthcare Needs

Prior to initiating any treatment, providers must complete a thorough review of

medical history; decide the best modality of treatment whether it be conventional
with or without nitrous oxide, conscious sedation, or general anesthesia; and pro-
vide local anesthetic when indicated. Providers may also consider ibuprofen (acet-
aminophen if kidney problems, bleeding issues, taking lithium, ibuprofen is
contraindicated with other medications taken, other medical issues that may contra-
indicate ibuprofen, or allergy to ibuprofen) 30 min prior to treatment to reduce
inflammation and the onset of sensitivity when local anesthesia becomes ineffective
(anesthesia disassociation discomfort).
Dentistry is an art. Each clinician comes with his/her set of strengths and chal-
lenges. This combined with the uniqueness of each patient needing treatment cre-
ates a labyrinth of options to navigate to make the best restorative recommendation.
Some restorations are more technique-sensitive, requiring a more cooperative
patient and seasoned clinician for success. For example, strip crowns, class II and
III tooth-colored restorations, and zirconia crowns (particularly posterior and back-
to-back with space loss and crowding) require advanced behavioral coaching and
clinical skill mastery to treat conventionally. Alternately, class I composites, amal-
gams, and stainless-steel crowns (all not as technique-sensitive) usually may be
successfully accomplished despite behavior and clinical experience.
Many clinicians do not venture beyond their training in their practice restorative
options. For example, despite being proven to be inferior to pre-veneered or zirconia
crowns in long-term parent satisfaction, many clinicians only place strip crowns as
this was the preferred choice restoration their faculty taught for anterior esthetic
crowns in primary teeth [6].
Finally, beyond the tooth, the modality of delivery of treatment chosen often
dictates treatment options given to parents. The literature states that long-term
262 E. L. Johnson and M. Guelmann

Fig. 16.2 Zirconia crowns

placed on primary molars
and pre-veneered stainless
steel crowns on primary
incisors

clinical success of full coronal coverage is more predictable than fillings for young
children treated in the operating room under general anesthesia [1].
Providers must be mindful to not predetermine care based on the patient’s socioeco-
nomic status, their training, and/or their preferred treatment to deliver. From a legal
standpoint, it is the responsibility of each provider to educate parents of all restorative
options and modality of delivery of care available for their children, whether they pro-
vide these services or need to refer to a provider who routinely provides these services.
The patient below (Fig. 16.2) was treated with nitrous oxide in office. Multiple teeth
required pulp therapy and the parent chose to place zirconia crowns on the posterior
teeth (that the insurance did not cover) and pre-veneered crowns on the anterior teeth
(that insurance did cover) to save money due to the understanding the posterior teeth
would be present significantly longer than the anterior teeth.
Patients requiring space maintenance may still choose zirconia crowns despite
knowing a metal band will be placed with the forward thinking of the band being
removed in the future. Clinicians must ensure parents understand if zirconia crowns
oppose stainless steel crowns, the zirconia will develop dark spots where the zirco-
nia occludes with stainless steel. These may easily be polished away; however, they
will return as long as the zirconia crown occludes with stainless steel (Fig. 16.3) [7].
Patients with special healthcare needs may require advanced imaging of the head
and neck area for various non-dental medical reasons. In these situations, a provider
must ensure their pediatric dental care does not compromise the diagnostic quality
of the imaging, particularly with magnetic resonance imaging (MRI). For example,
zirconia does not create artifact whereas stainless-steel crowns create significant
artifact [8]. A good option for providers not comfortable with zirconia crowns
restoring pulpally treated teeth on a child requiring MRI are large composites with
orthodontic bands placed over for extracoronal support and protection that may be
removed when an MRI is needed.
16 Restorative Guidelines for Endodontically Treated Primary Teeth 263

Fig. 16.3 Marks on zirconia

crowns when in occlusion
with stainless steel crowns

16.3 Isolation

Pulpal and restorative treatment success is enhanced with quality isolation. Rubber
dam isolation (RDI) remains the highest standard in isolation for pulp treatment and
restorative treatment in addition to the best infection control barrier from communi-
cable microbes such as the coronavirus. Rubber dam isolation is a fraction of the
cost of Isolyte®-type devices and provides the best consistent posterior depth of field
due to rubber dam clamp design. Retraction and protection of the soft tissue, and
view for the doctor and assistant are also superior with RDI. When using clamps
with wings placed in tandem with the rubber dam proper (advanced technique), trig-
gering the gag reflex can also be avoided or lessoned. The only downside to RDI is
that for the completion of a prep and final fit and cementation of a crown on the most
terminal erupted tooth being treated in a sequence, the rubber dam must be removed.
It is not uncommon for providers trained since Isolyte®/Isodry®/Isovac®-type tech-
nology has arisen to not become proficient in placing and training dental auxiliary
to place a rubber dam. There are myths that the placement of a rubber dam is less
efficient or more difficult for an anesthetized patient. Once placement is mastered,
RDI provides equally efficient isolation to Isodry®-type devices with equally com-
passionate placement. Below are enhancements to simple RDI to further increase
efficiency and meticulous isolation. The two rubber dam clamp technique for half-
mouth isolation offers providers the ability to prep teeth with a high speed hand-
piece, remove caries with a slow speed handpiece, treat the pulp, and restore two
quadrants at one time (Fig. 16.4). With younger children requiring treatment of first
permanent molars, sometimes space does not allow simultaneous isolation of both
upper and lower quadrants. It is also common when treating children conventionally
(no sedation nor general anesthesia) to only complete treatment in one quadrant.
Primary canines and incisors have ideal morphology with a well-defined con-
striction at the cemento-enamel junction to place floss ligatures to enhance isolation
for restoration success. The child shown below (Fig. 16.5a, b) had deep lingual car-
ies and received indirect pulp treatment. This child was treated in office with local
anesthetic, nitrous oxide, and oxygen and is an acceptable candidate for composite
resin restorations. This is due to evidence of compliance noted by further eruption
264 E. L. Johnson and M. Guelmann

Fig. 16.4 Rubber dam

isolation technique for
half-mouth approach
increasing efficiency

a b

Fig. 16.5 (a) Preoperative maxillary incisors and canines with deep lingual caries ready to be
restored with composite resin restorations. (b) Immediate postoperative outcome

of teeth without continued cervical demineralization, lack of caries on the incisal

edges, and conventional treatment (versus requiring general anesthesia where full
coronal coverage offers a more predictable long-term restorative outcome to avoid
future general anesthesia encounters).
The best indication for Isolyte® isolation is for sealant placement when local
anesthetic is not required (may still need the operculum gently retracted with a PF1
as shown below Fig. 16.6).
An additional benefit of Isolyte® is the ability to complete the preparation of the
distal aspect of the most terminal erupted tooth in the arch without removal prior to
crown cementation. However, providers must understand these devices in compari-
son to RDI limit handpiece maneuverability, dental assistant visibility, and also
16 Restorative Guidelines for Endodontically Treated Primary Teeth 265

Fig. 16.6 Isolyte® system

isolation facilitating
sealant placement on a
partially erupted first
permanent molar with PF1
retraction of operculum

increase expense. Additionally, not all children can tolerate these devices. In these
cases, the gag reflex, movement, and hypersalivation may compromise restorative
quality (nitrous oxide may help suppress the gag reflex).

16.4 Mouth Props and Bite Blocks

For safety, a mouth prop or bite block is recommended for children during local
anesthesia and restorative treatment (Fig. 16.7). For young children, the Molt type
mouth props are the standard. Another variation of the Molt type mouth prop is the
Denhardt mouth prop. The Denhardt is ideal for use when restoring anterior teeth.
The downside is that the lack of silicon sleeve makes it potentially uncomfortable
for children with shallow vestibules (shown Fig. 16.13c). Caution should be used to
ensure the lips and lingual frenum are free from impingement when using any Molt
type mouth prop, particularly in a child who has a numb lip or lips. In addition, the
provider must be cognoscente to ensure the silicon protective tubes do not slide off
and pose an airway issue.
A benefit of the Isolyte®-type isolation is the built-in mouth prop. Bite blocks are
more frequently used in teenagers or with children under conscious sedation or
general anesthesia where positioning is less contingent upon cooperation.
266 E. L. Johnson and M. Guelmann

Fig. 16.7 Molt type

mouth prop to maintain
mouth opening

16.5 Amalgam Restorations

Amalgam has a history of scrutiny and is not allowed in some countries, while in
others it is still permitted and readily used. It possesses qualities favorable for
restoring primary teeth with limited loss of tooth structure during indirect pup cap-
ping. Unlike composites, amalgam restorations’ seal may increase over time,
increasing their longevity [9].

Prepping keys Common errors Placement

Remove all caries/organic Inadequate isolation 1. Caries removal/pulp
material and/or affected hard Soft tissue penetration resulting in an treatment
tissue for caries and/or moderate amalgam tattoo 2. For class II: band system
to severe enamel For class II restorations: placed with wedging
hypomineralization (affected,  • Not dropping the gingival floor (sometimes 1–3 wedges of
even if non-carious, demineralized adequately (the interproximal varying sizing are needed for
tissue will be an area susceptible box must extend beneath the optimal band adaptation)
to new caries if hygiene, diet, and interproximal contact) often 3. Remove unsupported enamel
availability to fluoride are not results in recurrent caries at the rods at margin of the
ideal). The exception is a plan to contact in a high caries risk gingival floor and band with
treat with an indirect pulp cap patient an explorer or enamel
where caries are deliberately left  • Incomplete caries removal in the hatchet
to avoid pulp exposure. interproximal box 4. Triturate, pack, burnish, and
Utilize extension for prevention  • Overhang due to improper band carve amalgam
(enter grooves and ensure the fit, wedge placement, and/or lack 5. Check occlusion
adequate thickness of amalgam is of finish 6. Post-op polishing has lost
2mm or more to resist fracture) or  • Parent’s lack of understanding popularity due to knowledge
seal unaffected grooves with that the filling would not be tooth that warming the restoration
sealant material after amalgam colored may release mercury vapor
placement.  • Lack of discussion regarding the
Ensure that no undercuts or controversy of amalgam
unsupported enamel rods are
present to avoid enamel fractures.
16 Restorative Guidelines for Endodontically Treated Primary Teeth 267

16.6 Composite Resin and Compomer Restorations

Class I restorations may be utilized after IPC or, in rare situations, a pulpotomy with
a plan to place an orthodontic band over the restoration to enhance tooth resistance
to fracture. In that situation, a glass ionomer cement layer is needed to prevent
inhibited polymerization (when utilizing eugenol-containing products) or washout
of pulpal medicament. If the decision is made to place a composite in a tooth requir-
ing pulp treatment, enough tooth structure must be available to serve the patient
until exfoliation [10].
The images below are of the pre-op of a tooth treated with an IPC and composite
resin restoration, the 1 year post-op, and the 2 year post-op (Fig. 16.8a–c). This
example highlights deep caries with adequate tooth structure remaining circumfer-
entially to allow a filling versus a crown. This child had an isolated enamel defect
resulting in deep caries in one tooth rather than having poor oral hygiene and dietary
habits, a high caries risk, and multiple teeth requiring restorations.

a b c

Fig. 16.8 (a) Preoperative image showing deep carious lesion affecting the left mandibular sec-
ond primary molar (b) 1-year post-op of MTA IPC and composite restoration (c) 2-year post-op of
MTA IPC and composite restoration
268 E. L. Johnson and M. Guelmann

Prepping keys Placement

Remove all caries/organic material and/  1. Caries removal/pulp treatment/glass ionomer liner between
or affected hard tissue by caries and/or pulp treatment and composite (if eugenol-based pulp
moderate to severe enamel material is used or concern of washout of MTA)
hypomineralization. Affected, even if  2. For class II: band system placed with wedging (sometimes
non-carious, demineralized tissue will be 1–3 wedges of varying sizing are needed for optimal band
an area susceptible to new caries if adaptation)
hygiene, diet, and availability to fluoride  3. For class III: utilization of a clear strip and finger adaptation
are not ideal. The exception is a plan to  4. Remove unsupported enamel rods at margin of the gingival
treat with an indirect pulp cap when floor and band with an explorer or enamel hatchet
caries are deliberately left to avoid pulp  5. Wash and dry
exposure.  6. Etch 30 seconds with 37% phosphoric acid
Common errors  7. Bond, dissipate bond with air, cure agent 10-20 seconds (if
Inadequate isolation using a standard meter tested curing light)
For class II restorations resulting in  8. Composite placement: Flowable composite alone is acceptable
recurrent caries or further in limited shallow situations in primary teeth with class I
demineralization and loss of restoration: restorations (not acceptable for any restoration over a lesion
 • Not dropping gingival floor deep enough to warrant pulp treatment). Packable composite is
adequately (the interproximal box the standard for composite restorations. It is advisable to place a
must extend beneath the flowable layer before packable if an extensive lesion is present
interproximal contact) often results to reduce pull-back of the packable composite. It is also
in recurrent caries at the contact in a advisable to place a small amount of flowable in the
high caries risk patient interproximal box to reduce voids at margins that may not be
 • Incomplete caries removal in the visualized by the clinician.
interproximal box  9. Polymerization with meter tested curing light or lights from
 • Overhang due to improper band fit, two directions to reduce polymerization shrinkage (that may
wedge placement, and/or lack of finish create sensitivity) if it is a large restoration for 20-40
 • Incomplete polymerization in the seconds (if using standard curing light)
interproximal box resulting in an 10. Depending on the size of the prep, incremental composite
incomplete seal and leaking at axial curing may be needed and the use of two curing lights is
walls and gingival floor margins recommended. As a general rule, polymerization during curing
resulting in recurrent caries is ideal for 2mm; as an example, if you have an occlusal
Common errors in class III composite composite 4mm in diameter, a dental assistant and doctor
restorations: curing from buccal and lingual will create ideal
 • Relying on wedges to adapt clear polymerization. This applies to all surfaces.
strips may notch the interproximal 11. Provider should be mindful of dental assistants polymerizing
contour of the material and promote materials as their view and position may not be as ideal as the
gingival hemorrhage. In contrast, doctor and often the light is angled (causing inconsistent
finger pressure adaptation of the intensity) versus perpendicular to the material
clear strip best creates an ideal 12. Finish
contour and encourages bonding 13. Re-etch to remove the smear layer from finishing
without voids. 14. Seal to ensure no micro voids at the cavosurface margin
For class V composite restorations (clear seal for anterior teeth)
resulting in recurrent caries or further 15. Check occlusion
demineralization and loss of restoration: 16. If extensive tooth structure is removed, and full coronal
 • Lack of removal of the entire coverage with a crown is not possible, the placement of an
demineralized cervical aspect of the orthodontic band is recommended
lesion 17. Perforated metal strips are most efficient to finish the
 • Placed composites rather than full gingival margin of the interproximal box and interproximal
coverage crowns in noncompliant contacts. If a caries-free tooth has drifted into the tooth to be
patients with high caries risk restored due to caries, these strips may be useful to create
 • Not using retraction cord when more space in the mesial-distal dimension prior to restoring.
indicated, resulting in a marginal void Utilize the smooth (nonabrasive) area in the center of the
or crevicular fluid/hemorrhage strip to pass through the contact prior to engaging in
contamination smoothing the gingival margin of the interproximal box if it
 • Improper finish with ledge, flash, or is desired to maintain mesial-distal width and an ideal
roughness trapping plaque contact is present.
16 Restorative Guidelines for Endodontically Treated Primary Teeth 269

16.7 Composite Strip Crowns

Strip crowns commonly only provide temporary satisfaction with parents due to wear,
discoloration, recurrent caries, and esthetic failures. The patient below had strip
crowns placed under general anesthesia at age 2. Now at age 4, the parent is not satis-
fied with the esthetic presentation and was referred for zirconia crowns (Fig. 16.9).

Strip crown placement technique

 1. Choose a strip crown size prior to beginning the prep and consider the entire presentation of the
child’s mouth (space loss from caries, crowding, overbite, and overjet).
 2. Disking of the mesial surfaces of the primary canines may be necessary to provide the best
esthetics and address incisor liability. Complete this prior to initiating incisor prepping.
 3. Ensure the prep is complete, the pulp is treated as needed, and all enamel has been abraded
with diamond flame bur to enhance retention.
 4. Trim the crown as needed.
 5. Create a small hole or holes with a small bur on the incisal edge of the strip crown for
excess composite to escape.
 6. Wash and dry the tooth prior to strip crown try-in and ensure the strip crown is clean and dry.
 7. Manage hemostasis as needed (pressure, Superoxol, Astringedent™, etc.).
 8. Etch for 30 seconds with 37% phosphoric acid.
 9. Bond.
10. Place hybrid/packable composite in the strip crown.
11. Place the strip crown on the tooth, pressing firmly to engage all surface areas of the tooth.
12. Wipe the excess composite from the incisal edge and gingival margin (gently trying to
avoid gingival hemorrhage) with a composite instrument (PF1 has ideal angling).
13. Polymerize with meter-tested curing light or lights from facial and lingual to reduce
polymerization shrinkage (decreases potential sensitivity) if it is a large restoration.
14. The provider should be mindful of dental auxiliary polymerizing technique as their view
and access is not as ideal as the doctor’s and often the light is angled, causing inconsistent
intensity in contrast to that of being perpendicular to the material.
15. Use a scaler or caries excavation spoon to remove the strip crown.
16. Finish the cervical area with a finishing flame to ensure no overhangs and finish the incisal
edge where the composite was expressed during seating.
17. Perforated metal strips are best to finish interproximal areas and ideal for the contour of
line angles. Metal finishing strips may also be used to re-introduce embrasures if they were
lost with the strip crown anatomy.

Fig. 16.9 Strip crown on a

maxillary left central
incisor after 2 years
270 E. L. Johnson and M. Guelmann

16.8 Glass Ionomer Restorations

Glass ionomers have the same indications as composites, except they do not require
etching when used alone. It is important to understand that a child whose dental
disease has progressed to the point of requiring pulp therapy may not be the most
compliant of patients regarding follow-up. Some practitioners enjoy placing glass
ionomers as a temporary restorative measure (Interim Therapeutic Restorations-
ITR). However, it takes negligibly more time to complete a definitive restoration
and it is recommended, particularly in situations of pulp therapy to ensure the con-
tinued seal and success of the pulp therapy, esthetics, and continued asymptomatic
status of the child.

16.9 Sandwich Restorations (Glass Ionomer and Composite)

Glass ionomer with composite resin (the sandwich technique) is a good choice for
partially erupted teeth, subgingival caries in children who cannot get stainless-steel
crowns (due to special healthcare needs and the necessary use of an MRI), or chil-
dren who are not candidates for zirconia crowns (Fig. 16.10). Place a small incre-
ment of glass ionomer first if it is impossible to prevent crevicular fluid or blood
contamination at the gingival cavosurface margin due to partial eruption, gingivitis,
or subgingival caries. Then, complete the restoration with composite. Consider
placement of an orthodontic band for extracoronal support and to ensure long-term
restoration success.

Fig. 16.10 Sandwich

restoration (glass ionomer
and composite)
16 Restorative Guidelines for Endodontically Treated Primary Teeth 271

16.10 Stainless-Steel Crowns (SSCs)

Stainless-steel crowns have served the needs of children’s oral health for many
years with positive predictable outcomes and minimal patient cooperation and clini-
cian experience and skill needed. The only contraindications include nickel allergy,
the artifact it would create in a possible future MRI, and parents preferring the high-
est level of esthetics (wanting only tooth-colored restorative materials) [11].
Below is a child referred to a pediatric dentist after recurrent caries and loss of a
composite resin restoration. Illustrations below delineate the steps to the combina-
tion of MTA pulpotomy and stainless-steel crown placement (Fig. 16.11a–k).

a b c

d e f

g h i

Fig. 16.11 (a) Failed class II composite resulting in carious maxillary second primary molar
requiring vital pulp therapy and a stainless-steel crown. (b) Occlusal reduction opening access for
caries removal. (c) Pulp exposure after complete caries excavation. (d) Pulp chamber is unroofed.
(e) Pulpotomy performed using a round bur with a slow speed handpiece. (f) Sterile cotton pellets
for pressure hemostasis. (g) Complete heme control, ready for pulp medicament. (h) MTA is
packed in the pulp chamber. (i) Example of contour plier to assist on crown fitting. (j) Example of
crimping of crown margins to enhance retention. (k) Stainless-steel crown cemented and cleaned
272 E. L. Johnson and M. Guelmann

j k

Fig. 16.11 (continued)

MTA pulpotomy and SSC placement

 1. Choose a preliminary crown size prior to beginning the prep and consider the entire
presentation of the child’s mouth (space loss from caries, crowding, overbite, and overjet if
restoring primary anterior teeth [including canines with stainless-steel crowns or pre-
veneered stainless steel crowns])
 2. Reduce the occlusal/incisal surface and open pits and fissures to ensure access to caries
with a football diamond bur or other bur of choice.
 3. Complete caries removal with a slow speed handpiece using a 4 round or larger bur being sure
not to completely remove interproximal caries. This could create gingival hemorrhage prior to
the pulp being addressed (note exposure of the mesial-buccal pulp horn in illustration).
 4. Utilizing the football diamond (to eliminate a bur change) or a 330 carbide bur, unroof the
chamber and assess the visual presentation of the pulp (note that Fig. 16.11d is an ideal
presentation of a vital pulp).
 5. Remove the pulp from the chamber with a 4–6 size round bur in a slow speed handpiece
with copious irrigation utilizing sterile or treated water.
6. Pack sterile cotton pellets tightly for pressure hemostasis.
 7. Upon removal of sterile pellets, pulp stumps should not be hyperemic and the pulp
chamber should be clear of any pulp remnants or debris.
 8. Pack MTA firmly against the floor of the pulp chamber with damp cotton pellets ensuring
each pulp stump has the MTA sealed against it to promote dentinal bridging (a 2.0 mm
thickness of MTA is recommended). After pulp treatment, place glass ionomer cement
between pulp treatment and crown if there is concern of washout of the pulpal medicament.
 9. Only after pulp management should a provider continue with caries removal near the
interproximal gingival area or preparation of any portion of the crown that may create
gingival hemorrhage.
10. Step through interproximal surfaces using a 69 L or flame diamond or lighten the contact
with a football diamond in initial occlusal reduction and extension of grooves to expose the
caries (as shown in Fig. 16.11b to eliminate a bur change).
11. Create a feather edge circumferentially around the tooth using a flame diamond noting that
stainless-steel crowns generally require little, if any, buccal and lingual/palatal reduction.
12. Try on the crown.
13. Adjust the size as needed and utilize the hinge of a contour plier to reduce the crown width
mesial-distally in situations of space loss (versus a Howe or 110 plier that does not create
as ideal of a contour and may create divets that trap plaque) (Fig. 16.11i).
14. Utilize a crown crimping plier to tighten cervical collar to enhance crown fit.
15. Cement with a glass ionomer cement and ensure the crown is fully seated. In some situations,
when used with caution, a band pusher can assist in full seating. Although more expensive, brands
which provide an ampule automated mix option remove the mixing errors and increase efficiency.
Prior to filling the clean crown, fill the remaining portion of the chamber and access with cement
and then fill the crown, ensuring the cement is drawn up to the margins prior to placing.
16. Stainless-steel crowns adapted ideally will have a “snap” fit to create the best seal, reduced
cement washout, and long-term retention. Pre-veneered stainless steel crowns must have a
passive fit. Remove excess cement.
16 Restorative Guidelines for Endodontically Treated Primary Teeth 273

Fig. 16.12 (a) Preoperative images of a multiple primary molars with deep carious lesions requir-
ing pulp therapy and crown coverage. (b) 2-year postoperative showing radiographic success of
primary molars after MTA pulpotomies and stainless-steel crowns

The child below is an example of multiple teeth treated with MTA pulpotomies
and bitewing radiographs preoperatively and again 2 years after treatment was com-
pleted. A band-and-loop was removed prior to bitewing X-rays at this 2-year recare
appointment. Due to subgingival cervical caries, a size larger than planned was
required on tooth J (65). Note the MTA engagement with each of the pulp stumps to
create tiny “legs” radiographically (Fig. 16.12a, b).
Below is an example of full coronal coverage after MTA pulpotomy treatment
due to trauma to the chin (Fig. 16.13a). Treatment is the same for a pulpotomy due
to trauma as any pulpotomy and crown placement, with the exception of the fact that
there is no caries removal and it is only addressing the pulp and prep. The child had
an MTA pulpotomy versus a direct pulp cap or partial pulpotomy due to two weeks
passing after the parasymphysis trauma, resulting in a complicated oblique fracture
of tooth L (64) with pulpal exposure not diagnosed at the hospital (Fig. 16.13b). The
post-op film is 2 years after the initial injury (Fig. 16.13c).
274 E. L. Johnson and M. Guelmann

a b

Fig. 16.13 (a) Trauma to the chin. (b) 2 weeks post-trauma showing complicated crown fracture
on the mandibular left primary first molar. (c) 2 year post-op radiograph of the successful pulpot-
omy and stainless-steel crown coverage (note healing dentinal bridging)

16.11 Pre-veneered Stainless Steel Crowns

The technique is the same for pre-veneered SSCs as it is for traditional stainless-
steel crown preps, except these crowns may not be squeezed to reduce mesial-distal
crown width. Care must be taken to not crimp near the junction of the resin facing,
and these crowns should be placed with a passive, not snap fit, to ensure resin facing
is not flexed or compromised. These crowns may not be used with anterior crossbite
in occlusion or in children who have a habit of chewing on non-food objects. They
are an exceptional choice for maximum retention with minimal tooth structure
remaining due to the ability to crimp the lingual collar. Although lower incisor pre-
veneered crowns are not manufactured, it is possible to use uppers on lowers if size,
space, and overjet (or removal of maxillary anterior teeth) allows. The child below
had a submucosal cleft requiring oral intubation. After silver diamine treatment
arrested caries, only a pulpotomy was required to reach healthy pulp tissue in the
child, who was not a candidate for a pulpectomy due to incomplete root formation
(Fig. 16.14a–c).
16 Restorative Guidelines for Endodontically Treated Primary Teeth 275

Fig. 16.14 (a) Pre-op radiograph showing severe early childhood caries affecting maxillary pri-
mary incisors. (b, c) Intraoperative view before and after pulpotomy and complete pre-veneered
stainless steel crown coverage

16.12 Zirconia Crowns

Currently, zirconia crowns are the most durable and predictably-esthetic restoration
available for anterior and posterior teeth. The high strength resin polymer crowns
are esthetic and easier to place than zirconia; however, due to flexing properties,
these crowns will likely never achieve as superior of esthetic properties as zirconia.
Zirconia crowns may be used in any situation a SSC is indicated, pending the clini-
cian’s experience and comfort level. Zirconia crowns are especially useful in single,
double, and triple anterior crown needs whereas pre-veneered are not as esthetic
unless all four incisors are crowned. Zirconia crowns will not wear in a crossbite as
pre-veneered crowns will. The 2-year-old patient below had the first photo taken
immediately post-op (Fig. 16.15a) and the second photo 2 years later (Fig. 16.15b).
Due to the reverse nature in fitting in comparison to a stainless-steel crown where
the crown may be adapted to a tooth and its prep, a zirconia crown prep must be
adapted to the internal surface of the crown. This detail is what leads to the learning
curve for providers that is steeper than other crown preps. Clinicians may require
conscious sedation or general anesthesia to place zirconia crowns initially, particu-
larly in cases with space loss, back-to-back crowns, and/or full mouth cases.
276 E. L. Johnson and M. Guelmann

a b

Fig. 16.15 (a) Immediate post-op image of maxillary central incisors restored with zirconia
crowns. (b) 2-year post-op showing the crowns’ continued success, despite crossbite and inade-
quate oral hygiene

Zirconia crown placement

 1. Choose a preliminary crown size based on the mesial-distal dimension (utilize the “try-on”
crown if the brand has one to keep the definitive crown clean of debris and enhance the
bond).
 2. Reduce the occlusal/incisal surface by 2.0 mm and open pits and fissures to ensure access
to caries with a football diamond bur.
 3. Caries removal/with a slow speed handpiece and pulp treatment (glass ionomer cement
between pulp treatment if a eugenol-based pulp material is used or there is concern of
washout of MTA).
 4. Manufacturers recommend depth cuts with a chamfer bur to ensure adequate reduction and
then connection of depth cuts to create a chamfer margin circumferentially.
 5. Using a flame diamond bur, transition the chamfer margin to a feather edge margin.
 6. Final fit of try-on and prep adaptation (err on infra-occlusion versus supra-occlusion due to
the inability to create a snap fit).
 7. Cement (follow manufacturer’s cementation instructions) after remembering to fill the pulp
chamber and access and ensuring the cement is drawn up to the margins of the crown prior
to placing with a dual cure glass ionomer or hybrid cement and after 10–15 seconds of
dentinal tubule engagement spot cure.
 8. Remove excess cement and floss before final cure.
  9. Final cure and thorough cleaning.
10. If the opposing dentition is primary natural dentition, utilize a bur to make minor occlusal
adjustments on the opposing primary dentition or allow for natural occlusal equilibration.
11. Do not adjust zirconia crowns as this will create a spark and fire hazard as well as remove
the gloss that is responsible for enhanced esthetics and promotes easy removal of plaque.

Discoloration from MTA (if not non-staining brand) and silver diamine fluoride
will show through zirconia and must be completely removed prior to cementation if
the parent expectation is uniform color (Fig. 16.16a, b).
Unlike stainless-steel crowns, zirconia requires much more prepping. However,
this does not mean all teeth restored with zirconia require pulp treatment. Pulp
treatment is only indicated if needed for reasons outside of crown prepping. Parents
16 Restorative Guidelines for Endodontically Treated Primary Teeth 277

a b

Fig. 16.16 (a) Right maxillary central incisor showing a zirconia crown placed over treatment
with silver diamine fluoride. (b) Discolored zirconia crown on the mandibular left primary molar
as result of MTA (not non-staining brand) staining

a b

Fig. 16.17 (a) Preoperative view of early childhood caries. (b) Immediate post-op after zirconia
crown restorations placed on maxillary incisors, maxillary canines, maxillary and mandibular
­primary molars. (c) One-week post-op view

must understand, particularly in situations such as the child below with extensive
cervical caries requiring pulp treatment (Fig. 16.17a), that the tissue will look trau-
matized immediately postoperatively (Fig. 16.17b). As zirconia is more tissue-
friendly than any other crown material, it will heal rapidly (Fig. 16.17c). Below is
a patient preoperative, immediately postoperative, and at a 1-week surgical
follow-up.
278 E. L. Johnson and M. Guelmann

16.13 Final Tips

In situations of severe early childhood caries, providers need to think comprehen-

sively about the needs of the child, desires of the parents, materials available, their
skills and comfort level in restorative options, and their skills and comfort level in
care delivery modality (conventional to general anesthesia). When teeth are severely
broken down and require extensive pulp therapy and restorative, it is key to begin in
the posterior on one side (particularly under general anesthesia) to regain vertical
dimension prior to moving to the anterior. This will prevent inadvertent maxillary
incisor flare when restoring anterior teeth that may be in occlusion with lower ante-
rior teeth prior to regaining the vertical dimension. Providers must also be mindful
not to create functional interferences resulting in crossbite with crown placement of
primary canines. Unlike the stainless-steel crown below, a zirconia crown will not
wear (Fig. 16.18).
Occlusion is difficult to check under conscious sedation and general anesthesia.
It is a good practice to err on infra-occlusion with primary canines during zirconia
cases. Better yet, Dr. Ron Bell, a dual board-certified pediatric dentist and orthodon-
tist, coined the term “Cuisinart Dentistry”. This is the mesial and distal disking of
caries or simple space borrowing from primary canines (assuming the pulp as well
as facial and lingual surfaces were not involved) to better allow addressing first
primary molars pulpally and restoratively to fully save the space for the first premo-
lar in the future. This technique may also allow incisor crowns to be placed more
esthetically. This technique also makes it possible to place zirconia crowns in situa-
tions of significant space loss from caries. Similarly, an over-prepping, or early use
of E-space of the second primary molar with more predictable pulp morphology
may lend to the ability to best pulpally and restoratively treat a first primary molar
that at first glance may appear non-restorable.
Fig. 16.18 Traumatic
occlusion over stainless-
steel crown creating wear
of the crowns
16 Restorative Guidelines for Endodontically Treated Primary Teeth 279

Restorative options for primary teeth requiring endodontic treatment

Fillings Full coronal coverage
 • Anterior and posterior teeth  • Any pulpectomy
requiring indirect pulp caps for 1 or  • Any pulpotomy
2 surfaces in children who may be  • Any tooth in a young child treated with
treated without conscious sedation conscious sedation or general anesthesia
or general anesthesia or <2 years to  • 2 or more surfaces with an indirect pulp cap
exfoliating the teeth  • Any tooth requiring pulp treatment with
 • Posterior teeth treated with indirect >2 years to exfoliation
pulp caps or pulpotomy for class I  • Any tooth that the child’s cooperation does not
lesions with interproximal surfaces predict positive clinical outcome for a filling
intact (recommended if >2 years to  • Any tooth with a failed filling due to recurrent
exfoliation to place an orthodontic caries, gastroesophogeal reflux disease, or habits
band for long term extracoronal  • Any anterior tooth involving the incisal edge
support)

16.14 Conclusion

Restoring mouths of children with significant dental disease requiring pulp therapy
can be challenging. The great news is that it gets easier with experience, provided
that the clinician continues lifelong learning utilizing evidence-based pulpal and
restorative materials available to them. The clinician may need to embrace learning
curves with materials that were not available to them in their training. Doing so will
provide their patients with optimal contemporary esthetic restorative care.

References
1. American Academy of Pediatric Dentistry. Pediatric restorative dentistry. The reference
manual of pediatric dentistry. Chicago, IL: American Academy of Pediatric Dentistry; 2021.
p. 386–98.
2. Berg JH. The continuum of restorative materials in pediatric dentistry—a review for the clini-
cian. Pediatr Dent. 1998;20(2):93–100.
3. Guelmann M, Mjör IA. Materials and techniques for restoration of primary molars by pediatric
dentists in Florida. Pediatr Dent. 2002;24(4):326–31.
4. Waggoner WF. Restoring primary anterior teeth: update for 2014. Pediatr Dent.
2015;37(2):163–70.
5. Guelmann M, Shapira J, Silva DR, Fuks AB. Esthetic restorative options for pulpotomized
primary molars. J Clin Pediatr Dent. 2011;36(2):123–6.
6. Manmontri C, Sirinirund B, Langapint W, Jiwanarom S, et al. Retrospective evaluation of the
clinical outcomes and patient and parental satisfaction with resin strip crowns in primary inci-
sors. Pediatr Dent. 2018;40(7):425–32.
7. Donly KJ, Sasa I, Contreas CI, Mendez MJC. Prospective randomized clinical trial of primary
molar crowns: 24-months results. Pediatr Dent. 2018;40(4):253–8.
8. Mathew CA, Maller S, Maheshwaran. Interaction between magnetic resonance imaging and
dental material. J Pharm Bioallied Sci. 2013;5(Suppl 1):S113–6.
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9. Fuks AB. The use of amalgam in pediatric dentistry: new insights and reappraising the tradi-
tion. Pediatr Dent. 2015;37(2):125–32.
10. Guelmann M, Mcllwain MF, Primosch RE. Radiographic assessment of primary molar pulp-
otomies restored with resin-based materials. Pediatr Dent. 2005;27(1):24–7.
11. Seale NS, Randall R. The use of stainless steel crowns: a systematic literature review. Pediatr
Dent. 2015;37(2):145–60.
Endodontic Treatment for Young
Permanent Teeth 17
Eyal Nuni and Iris Slutzky-Goldberg

Contents
17.1  actors Affecting the Treatment of Young Permanent Teeth
F 282
17.1.1 Pulp Characteristics of Immature Permanent Teeth 282
17.1.2 Nature of Pulp Damage 282
17.1.3 Stage of Root Development 283
17.1.4 Restorability 283
17.2 Pulpal and Apical Diagnosis 284
17.2.1 Clinical Examination 285
17.2.2 Pulp Sensibility Tests 285
17.2.3 Radiographic Examination 288
17.2.4 Pulpal and Apical Tissue Diagnostic Terminology 289
17.3 Materials Used in Vital Pulp Therapy 290
17.3.1 Sodium Hypochlorite (NaOCl) 290
17.3.2 Ethylenediaminetetraacetic Acid (EDTA) 291
17.3.3 Calcium Hydroxide [Ca(OH)2] 291
17.3.4 MTA- and Calcium Silicate-Based (CSB) Materials (Bioceramics) 292
17.4 Pulpotomy 293
17.4.1 Clinical Procedure: Partial and Cervical Pulpotomy 295
17.4.2 Bleeding Time 297
17.4.3 The Expected Outcome 297
17.4.4 Pulpotomy with Different Materials 297
17.4.5 Timing of Pulpotomy After Traumatic Injuries 298
17.4.6 Prognostic Factors 298

E. Nuni
Department of Endodontology, The Maurice and Gabriela Goldschleger School of Dental
Medicine, Tel Aviv University, Tel Aviv, Israel
e-mail: [email protected]
I. Slutzky-Goldberg (*)
Department of Endodontics, Galilee College of Dental Sciences, Nahariya, Israel
Faculty of Medicine, Bar-Ilan University, Ramat Gan, Israel

© The Author(s), under exclusive license to Springer Nature Switzerland AG 2023 281
A. B. Fuks et al. (eds.), Contemporary Endodontics for Children and
Adolescents, https://doi.org/10.1007/978-3-031-23980-9_17
282 E. Nuni and I. Slutzky-Goldberg

17.5 Regenerative Endodontics 299

17.5.1 Clinical Procedure 299
17.5.2 Scaffold 302
17.5.3 Follow-Up 302
17.5.4 Expected Outcome 302
17.5.5 Survival 303
17.5.6 Pulp Regeneration 304
17.5.7 Tissue Reactions 305
17.5.8 Influence of Apical Diameter on the Outcome of Revascularization 305
17.5.9 Comparison of Revascularization and Apexification 306
17.6 Root Canal Treatment in Young Permanent Teeth and Apexification 306
17.6.1 Clinical Procedure 307
References 311

A young permanent tooth is a recently erupted permanent tooth with incomplete

root formation. These teeth may present different stages of root development rang-
ing from a tooth with a wide root canal, open apex and thin walls, to a fully devel-
oped root with a slightly open apex [1].
Injury to the dental pulp of immature teeth is usually a result of dental trauma or
a carious lesion.
The main objective of treatment in young permanent teeth is to preserve the tooth
involved in the dental arch to allow proper maxillofacial development.
The endodontic treatment of young teeth is complex and challenging because of
the unique characteristics of these teeth.

17.1 Factors Affecting the Treatment of Young

Permanent Teeth

17.1.1 Pulp Characteristics of Immature Permanent Teeth

The dental pulp is a connective tissue of mesenchymal origin encased in a rigid

chamber consisting of enamel and dentin [2]. In young teeth, the pulp space is wide
and contains loose connective tissue rich in blood vessels and cells. This pulp tissue
has high healing potential as it manifests superior cell proliferation and differentia-
tion and the formation of blood and lymphatic vessels. The defense mechanism in
the young pulp is more developed and potent. These characteristics are regulated by
various extracellular matrix (ECM) bioactive molecules and growth factors [3].

17.1.2 Nature of Pulp Damage

Pulp injury can result from damage to the blood supply (dental trauma, excessive
orthodontic forces, etc.) or damage to the protective enamel and dentin layer (e.g.,
crown fracture, caries, developmental malformation, MIH) [4]. Pulp reaction to
17 Endodontic Treatment for Young Permanent Teeth 283

injury due to caries is different from traumatic injury. Changes in the pulp after
exposure to caries result from the ingress of bacteria and their endotoxins. The
inflammation of the pulp is accompanied by tertiary dentin formation [5]. However,
after a traumatic dental injury, the depth of inflammation is limited to the superficial
area of the pulp. Cvek demonstrated in 1982 that after pulp exposure due to compli-
cated crown fracture, the depth of inflammatory cell infiltration after 7 days was
only up to 2.2 mm with a hyperplastic defensive tissue reaction [6, 7].

17.1.3 Stage of Root Development

The stage of root development is a significant factor in the pulp’s ability to heal and
the determination of the appropriate treatment. Nolla classified the degree of tooth
maturation in 1960; this classification is based on the radiographic evaluation and
includes ten stages. Stages 7 refers to only one-third of the root completed, whereas
stage 10 describes the fully developed root [8]. Understanding the stage of root
development may aid in treatment decisions. The more immature the root, the
younger the pulp; therefore, its healing potential is more prominent (see above).
Furthermore, the blood supply to the pulp tissue flows through the apical foramen
with no collateral blood vessels [2]. In a mature tooth, when the blood supply is
damaged, pulp necrosis is expected, while in a young tooth with an open apex,
recovery and even revascularization after pulp necrosis is possible, thus maintaining
pulp vitality [9, 10].
The immature tooth may be characterized by thin dentinal walls and an unfavor-
able crown-root ratio [11, 12]. These teeth are more prone to trauma, especially in
the cervical area. Cervical fracture is possible even as a result of masticatory forces
[11]. Therefore, in younger, less mature teeth (Nolla stage 7 or 8), (Fig. 17.1b), it is
imperative that the treatment plan will aim to enable maturogenesis. Furthermore,
the susceptibility of the immature tooth to infection is increased due to the thin
dentinal walls and the wide tubuli resulting in inflammatory root resorption after
pulp necrosis [13].

17.1.4 Restorability

The treatment plan is directed by the extent of coronal damage and the ability to
restore the tooth. Traditionally, the restoration of widely damaged teeth required the
placement of a core and post, thus necessitating a root canal treatment. It is now
well accepted that a 2 mm ferrule is more important than the post and core, thus
enabling a more conservative approach to the teeth restoration [14].
An orthodontic evaluation is required, especially in teeth with poor restorative
prognosis. Factors such as teeth crowding in the developing dentition may influence
the decision to treat or extract the injured tooth. Moreover, early extraction of the
damaged tooth may enable the eruption of the adjacent tooth into the extraction site,
284 E. Nuni and I. Slutzky-Goldberg

a b c d

f
e g h

Fig. 17.1 Deep pulpotomy with Ca(OH)2. (Courtesy: Dr. Eyal Nuni). (a) An 11-year-old boy
complaining of spontaneous severe pain (irreversible pulpitis) has been taking analgesics for the
last 4 days. Occlusal view of the second lower left premolar. A gray discoloration can be seen
mesial to the transverse ridge. (b) Preoperative radiograph presenting pre-eruptive intra-coronal
resorption, an immature root with very wide apical foramen (Nolla stage 7). (c) The resorptive
lesion after access cavity preparation. (d) Pus drainage after pulp exposure. (e) Pulp tissue hemo-
stasis after deep amputation. (f) Post-op radiograph calcium hydroxide placed on the pulp tissue
and covered with Fuji IX™ glass ionomer. (Use of Ca(OH)2 was decided to enable re-entry, con-
sidering the depth of pulp amputation). (g) 4.5 years’ follow-up. Root development is almost com-
plete. Hard tissue barrier in the middle of the root. The calcium hydroxide has been completely
dissolved. A small apical radiolucency is present. (h) The contralateral radiograph demonstrates
complete root development of the contralateral tooth. (i) CBCT demonstrating the incomplete hard
tissue barrier (arrow) and the anatomy of the open apex

especially when maxillary molar teeth are involved. Extraction of hypo-mineralized

teeth affected by MIH and spontaneous eruption of the second molar is an excellent
treatment alternative, mainly if performed before the eruption of the tooth [15].

17.2 Pulpal and Apical Diagnosis

Diagnosis of the pulp status is critical in determining the appropriate treatment of

young permanent teeth. However, it is also the most difficult to establish. There are
discrepancies between the pulp clinical diagnosis based on clinical signs and
17 Endodontic Treatment for Young Permanent Teeth 285

symptoms, radiographic examination, and the histologic findings [10]. Furthermore,

children’s reaction to diagnostic tests such as cold, palpation, and percussion can be
excessive and does not reflect the actual sensation [16, 17].
Upon arrival at the dental clinic, the patient or legal guardian should complete
and sign a full medical and dental history form. The clinician will review the form
with the patient and enquire about the chief complaint, the events that led to it, and
to the visit.

17.2.1 Clinical Examination

The clinical examination includes extra- and intra-oral examinations and tests.
When clinical examinations are performed, contralateral and adjacent teeth should
be tested first as a control. Extra-oral swelling along with sensitive and enlarged
lymph nodes on palpation may indicate the presence of extra-radicular infection as
a result of pulp necrosis. Intraoral swelling can also point to pulp necrosis and more
localized infection. Any swelling should be palpated to determine whether it is firm
or fluctuant and whether it is localized or diffused. Chronic endodontic infection
can drain through an intra- or extra-oral sinus tract. The sinus tract must be traced
(usually using a gutta-percha point #30) in order to determine the origin of the
infection [18, 19] or by inserting an orthodontic wire through an extra-oral
sinus tract.
A percussion test may help to isolate the source of the pain as it indicates an
inflammation of the periodontal ligament, mediated by nociceptive mechanism
[20]. This may be a result of periapical disease or food impaction; however, percus-
sion sensitivity does not accurately reveal the pulpal status. Teeth can become ten-
der for reasons other than an endodontic disease, such as maxillary sinusitis,
hyperfunction, dentoalveolar pain disorder, or orthodontic movement [21].
Periodontal and mobility tests are significant although they also do not indicate
pulp vitality. Deep isolated periodontal probing is an indication of bone loss that can
be a result of pus drainage from the periapical area of a non-vital tooth. Increased
mobility can be a result of numerous reasons including periodontal disease, para-
functional habit, orthodontic forces, physical trauma, and infection of the periodon-
tal ligament as a result of pulp necrosis [18].

17.2.2 Pulp Sensibility Tests

Pulp sensibility tests are an important factor influencing diagnosis and treatment.
These tests are more challenging in children as their ability to comprehend and
express the sensation is limited. Thermal tests (cold or hot), electric pulp testing
(EPT), and direct dentin stimulation (cavity/drill test) are the most prevalent meth-
ods. These tests do not indicate the vitality (blood circulation) of the tissue and
rather indicate neural response of the tissue. Some studies suggest that these tests
cannot be used to identify the degree of inflammation in the pulp but rather assess
whether the pulp is vital or necrotic. False-positive and false-negative results can
286 E. Nuni and I. Slutzky-Goldberg

also occur, for example, after dental trauma or as a result of inadequate isolation.
These tests can be helpful in locating the diseased tooth by replicating its symptoms
[22]. It is recommended that additional findings such as crown discoloration and
radiographic evidence of a periapical lesion should support the lack of sensibility
when determining pulp necrosis in dental trauma cases [23]. All sensibility tests
require isolation of the examined tooth to receive a reliable response. In thermal and
EPT, before testing the suspected diseased tooth, the contralateral tooth and then a
tooth that is considered normal adjacent to the suspected diseased tooth should be
assessed. If possible, the test should be repeated after a 1-min recovery for a more
objective result [22].

17.2.2.1 Thermal Tests

Normal response to thermal test (cold or hot) is a sensation that disappears immedi-
ately after the removal of the stimulus. Prolonged pain, no sensation, acute pain, and
immediate severe pain are considered abnormal [18].

Cold Test
Cold test is the most frequent thermal test used today as it is easy to perform, readily
available, reproducible, and reliable. Cold spray is mostly used as a means to pro-
voke the stimulus although CO2 snow stick is a very reliable tool as well; however,
its manipulation is less convenient [24]. Cold application stimulates the fast-­
conducting Aẟ nerve fibers, thus producing a sharp localized pain. The test does not
injure the pulp or cause damage (e.g., cracks) to the hard tissues [22]. The cold
spray is applied to the tooth with a #2 cotton pellet touching the buccal surface [18,
25]. It should be taken into consideration that a multirooted tooth can respond to
cold testing although the pulp tissue in some of the canals can be necrotic [26].

Heat Test
Heat application stimulates the slow conducting C nerve fibers located deep in the
pulp, thus producing dull lingering pain. Although having a greater potential for
pulp damage, the application of the heat source correctly will not injure the tissue.
Heat can be applied by placing a warm gutta-percha stick on the buccal aspect of the
isolated tooth or by applying hot water via a syringe after placing a rubber dam.
Heat tests are most effective when the patient’s main complaint is pain from hot
stimuli. In these cases, the test will enable locating the tooth by reproducing the pain
sensation [18, 22].

17.2.2.2 Electric Pulp Test (EPT)

EPT stimulates the Aẟ nerve fibers by producing sufficient electric current to over-
come enamel-dentin resistance [27]. In order to obtain a reliable test result, strict
isolation (e.g., rubber dam) is needed. Without isolation stimulation of the adjacent
teeth or periodontal ligament with the electric current can induce a false-positive
response. None of the studies available indicated whether the readings on the device
numerical display are reproducible and have any significance [22].
17 Endodontic Treatment for Young Permanent Teeth 287

Nevertheless, a recently published paper evaluated the response of 1200

young permanent incisors in patients aged 6–12 to EPT. The EPT reading
decreases with the development of the tooth. Regardless of the stage of root
development, the lowest EPT thresholds were obtained when the EPT probe was
placed on the incisal third of the crown [28]. This was attributed to the fewer
number of mineralized axons in the immature pulp. Until innervation is com-
pleted (4–5 years of tooth in function), the electric pulp test is not a reliable
means for determining tooth vitality [29].
Whereas all 1200 incisor teeth in patients aged 6–12 responded positively to
EPT, the electric pulp testing was less reliable than Endo Ice and CO2 snow in young
patients (9–13) with immature premolars [28, 29]. Furthermore, Bastos et al. dem-
onstrated that in traumatized young teeth (patients mean age 10.6 ± 3.3) the EPT
was more reliable than cold testing with Endo Frost (Roeko, Langenau, Germany)
or heat testing with gutta-percha. The authors reported a temporary loss of sensibil-
ity, especially after luxation injuries. The time until a positive response to sensibility
testing was obtained ranged between 2 and 67 months [30].
When a negative response is obtained, EPT is most accurate in predicting pulp
necrosis in any current intensity [31]. Weislede et al. (2009) demonstrated that when
the EPT was used in combination with Endo Ice and CO2 snow, the results were
more accurate compared to the use of each of the tests separately [32]. Using EPT
and cold test together will corroborate the result of each individual test. A negative
response to both tests in a mature tooth will most likely indicate that the tooth is
necrotic [33, 34].

17.2.2.3 Laser Doppler Flowmetry (LDF)

LDF is a method to assess the presence or absence of blood flow in the dental pulp
tissue by projecting an infrared light beam through the crown. It has some signifi-
cant advantages compared to other test modalities as it is accurate, reliable, objec-
tive, reproducible, and not painful or does not induce damage to the pulp tissue
[35–38].
LDF was found to be a highly reliable method in order to determine the pulpal
health status. The stage of root development did not affect the reliability of the test.
Alghaithy et al. advocated the use of LDP for clinical situations in which pulp sen-
sibility tests are expected to be unreliable, particularly following traumatic dental
injuries [24]. The limitation to the use of the LDF is its availability in dental offices
and the fact that it is still cumbersome and requires a complicated procedure.

17.2.2.4 Test Cavity (Drill Test)

Test cavity is used only as a last resort in cases where the test results are inconclu-
sive or when other sensibility tests are impossible to use. This test is invasive and
irreversible. A small class 1 cavity preparation in posterior teeth or a palatal cavity
in anterior teeth is drilled with a high-speed bur and copious water spray without
anesthesia. If the patient reports pain when the preparation reaches dentin, the tooth
is presumed vital, and the cavity preparation is restored. If no pain is provoked, the
288 E. Nuni and I. Slutzky-Goldberg

tooth is necrotic and root canal treatment is indicated. This test reflects the presence
of functioning nerve fibers and not blood circulation in the pulp and is also very
subjective; therefore, care should be taken while performing the test and interpret-
ing its results [39]. Occasionally, the test cavity reaches the pulp, which appears to
be normal. In these cases, a direct pulp capping should be indicated. This procedure
should be questioned in apprehensive young patients and may affect any future
cooperation; thus, it should be performed only in rare cases [39].

17.2.3 Radiographic Examination

Radiographic examination can include several types of X-rays and in some cases
more advanced imaging modalities such as cone-beam computed tomography
(CBCT). It is an integral part of the diagnostic process and should be considered in
conjunction with the rest of the information gathered to achieve correct diagnosis
and prognosis. The appropriate diagnostic image should be achieved using ade-
quate exposure parameters to estimate anatomy and pathologic processes or condi-
tions such as peri-radicular disease. Diagnostic radiographs should be taken only
after reviewing the patient’s health and dental history and a thorough clinical
examination [40].
The patient, especially young children, should be exposed to the minimal radia-
tion necessary [40]. However, for detecting endodontic pathosis, two diagnostic
radiographs are often required. Usually bitewing and periapical radiographs (e.g.,
for detecting caries depth, furcation involvement, and periapical status), two radio-
graphs from different angulations (e.g., detecting the roots morphology), or radio-
graph of the contralateral tooth (e.g., to assess stage of root development) of the
suspected tooth [18] (Fig. 17.1h).
The International Association of Dental Traumatology (IADT) recommends tak-
ing up to four radiographs in every trauma case [41]. In some trauma cases such as
root fracture, an occlusal radiograph is indicated for better diagnosis.
Digital radiographs are recommended as they have important advantages such as
low radiation, easy to obtain, no chemical processing, instant viewing, manipulation
possibilities, and easy to send [18].
It was previously thought a radiolucent PA lesion which is a result of pulp necro-
sis can be detected in a radiograph only when bone lose extends to the junction of
the cortical and cancellous bone [42]; however, it was later demonstrated that peri-
apical lesions can be diagnosed from periapical radiographs before they have eroded
the cortices while they are still limited to the cancellous bone [43].
Pulp pathosis may be present even when it cannot be demonstrated in the PA
radiograph and can only be detected in CBCT images [44]. Furthermore, radio-
graphic interpretation is highly subjective and varies depending on the clinician
[45, 46].
In young permanent teeth, some conditions can mimic the appearance of patho-
logic apical radiolucency as a result of pulp necrosis (Fig. 17.1). Teeth with incom-
plete root formation demonstrate apical radiolucency representing the normal apical
17 Endodontic Treatment for Young Permanent Teeth 289

papilla. Therefore, in case there is doubt as to the periapical diagnosis, comparison

should be done with the image of the contralateral tooth. Also, in trauma cases tran-
sient apical breakdown (TAB) can be present manifesting periapical radiolucency
and sometimes negative response to cold test and crown discoloration; these charac-
teristics are reversible [47].
Panoramic radiographs can be advised in various conditions. For example, when
a large finding is present, to see its full dimensions or when an overall evaluation of
the oral cavity is needed. It is also suggested when the first permanent molar has a
questionable prognosis and its replacement by the second molar is considered, the
presence of a normal tooth bud can be demonstrated in the panoramic view. In cases
when intra-oral radiographs are impossible to take, as a result of a gag reflex or poor
patient cooperation, panoramic or extra-oral radiographs can be helpful [48].

17.2.3.1 CBCT
CBCT has become an important and common tool in dentistry and endodontic prac-
tice since it was first introduced at the beginning of the twenty-first century [49].
It enables three-dimensional imaging allowing the dentist to observe the tissues
in multiple planes. When indicated CBCT should be used as an adjunct diagnostic
tool in addition to intraoral radiography and not as a replacement. It is a valuable
instrument in assessing periapical pathosis, dental trauma, anomalies in the devel-
oping dentition, oral pathology, etc. [40] (Fig. 17.1i).
Clinical guidelines for the use of dental radiographs and CBCT in children and
adolescents [40] and in endodontics [50] were published. As in all imaging modali-
ties, the ALARA (As Low As Reasonably Achievable) principle should be imple-
mented when considering the use of CBCT, especially in children who are more
prone to radiation damages [51].
Every case should be assessed individually in regard to selection of the use of
CBCT. The benefits of the 3-D imaging should outweigh the potential risks and may
be considered when conventional radiographs are inadequate to complete diagnosis
and treatment planning [50, 52].

17.2.4 Pulpal and Apical Tissue Diagnostic Terminology

Endodontic diagnosis of the pulp and apical tissues is based on clinical and radio-
graphic findings. This is elaborated in further detail in the glossary of endodontic
terms published by the AAE [53]. The pulpal status was traditionally defined as
either normal, reversible, or irreversible, referring to the ability of the vital inflamed
pulp to heal. Later a differentiation was made between symptomatic or asymptom-
atic irreversible pulpitis. The diagnosis is based on objective and subjective findings.
According to the AAE glossary of terms, whereas in asymptomatic irreversible
pulpitis, the inflammation is caused by caries, caries excavation, or a traumatic
injury, without any clinical symptoms. Symptomatic irreversible pulpitis is accom-
panied by lingering thermal pain, spontaneous pain, or referred pain. In both cases,
the pulp is incapable of healing [53]. However, since pulpitis is a progressive
290 E. Nuni and I. Slutzky-Goldberg

disease, this classification does not refer to the gradual progression of the disease in
the pulp, nor to the ability to remove only the diseased tissue, thus enabling the
remaining pulp to heal. Therefore, the current classification does not enable the
practitioner to assess the treatment outcome.
Wolters et al. in 2017 introduced a new classification system. This classification
includes four stages of pulpal disease: initial, mild, moderate, and severe [54].
Initial pulpitis is characterized by prolonged response to cold testing without any
additional findings. In case of mild pulpitis, there is a prolonged reaction to thermal
stimuli, which can last up to 20 s and a possible sensitivity to percussion.
Histologically, the inflammation is limited to the coronal pulp. Moderate pulpitis is
marked by a longer response to thermal testing which can last for minutes. It may
be accompanied by sensitivity to percussion and a spontaneous dull pain. The pain
can be managed by analgesic medications. Histologically, extensive local inflam-
mation confined to the coronal pulp can be expected. In severe pulpitis, a severe
spontaneous pain with a strong reaction to thermal stimuli is often accompanied by
throbbing pain. The patients complain of trouble sleeping that can be aggravated
when lying down. The tooth is sensitive to percussion. A more extensive inflamma-
tion which may extend into the root canals may be reflected histologically. The
authors suggest that the type of treatment should be adjusted to the diagnosis. Mild
pulpitis can be treated by indirect pulp treatment. Partial or cervical pulpotomy is
suggested in cases of moderate pulpitis, whereas cervical pulpotomy can be consid-
ered in severe pulpitis. Nevertheless, when the bleeding cannot be controlled, pulp-
ectomy is indicated [54]. This suggested diagnoses and treatments should serve as
general guidelines by the prudent clinician when treating the inflamed pulp.

17.3 Materials Used in Vital Pulp Therapy

17.3.1 Sodium Hypochlorite (NaOCl)

Sodium hypochlorite is the most common irrigation solution used in endodontics. It

is usually used for root canal irrigation because of its effective antimicrobial and
tissue-dissolving properties. It is used in various concentrations usually between 0.5
and 5.25% [55].
Currently it is also considered the most effective material used in vital pulp ther-
apy for rinsing during the treatment and for hemostasis of the pulp tissue [56]. It
disinfects the dentin and pulp, promotes hemostasis, and dissolves blood clots.
Irrigation with NaOCl removes infected dentin chips and tissue remnants [57]. The
presence of a blood clot may lead to internal resorption and dystrophic calcifica-
tions, serve as a substrate for bacteria in leaking restoration, and damage dentin
bridge formation, thus compromising the treatment outcome [58]. Rinsing with
sodium hypochlorite does not damage the pulp tissue or impair the ability to recruit
pulp cells, their differentiation, and hard tissue deposition [59]. The ability to
17 Endodontic Treatment for Young Permanent Teeth 291

control the bleeding after rinsing with NaOCl for 10 min can distinguish between
reversible and irreversible pulpitis, and continuous bleeding is considered a sign of
irreversible inflammation [57].

17.3.2 Ethylenediaminetetraacetic Acid (EDTA)

EDTA, a polycarboxylic amino acid, is one of the irrigation solutions used in end-
odontic procedures. This chelating agent removes the inorganic component of the
dentin and smear layer [60]. It is used in a 17% concentration. It has an antibacterial
effect which is stronger than 0.5% sodium hypochlorite but weaker than 2.5%
sodium hypochlorite [61]. EDTA exerts its strongest effect when used synergisti-
cally with sodium hypochlorite [62]. Studies have demonstrated that EDTA can
solubilize dentine matrix components, shows morphogenetic activity, and can
induce reparative dentinogenesis [63].
Irrigation protocol combining sodium hypochlorite and EDTA enables the
release of growth factors, cytokines, and other bioactive molecules required for den-
tinogenesis [64].

17.3.3 Calcium Hydroxide [Ca(OH)2]

Calcium hydroxide was considered the gold standard material for intracanal medi-
cation and vital pulp therapy. Nevertheless, more recent studies questioned its effec-
tiveness in further eliminating bacteria as a root canal dressing material [65–67].
For both purposes, it is usually mixed with sterile water or saline and dissolves into
Ca++ and OH− ions. Its main properties include high pH (12.5–12.8), low solubil-
ity, tissue dissolution, long-term wide range antimicrobial activity, and inactivation
of endotoxin [65].
The main drawbacks of Ca(OH)2 are associated with its physical properties. This
non-setting material will go through degradation and dissolution over time, leading
to infection when coronal leakage is present (Fig. 17.1g). Furthermore, exposure of
dentin to Ca(OH)2 especially for long periods reduces its flexural strength and low-
ers its fracture resistance [65]. Ca(OH)2 capping during vital pulp therapy in young
permanent teeth is also associated with calcifications of the pulp, which makes
future root canal treatment when needed difficult or even impossible [68].

17.3.3.1 Hard Tissue Formation

Calcium hydroxide’s high alkaline values have been shown to cause fibroblast and
enzyme stimulation, pulp tissue defense mechanisms and repair activation, as well
as hard tissue formation in cases of pulp capping and apexification. In direct contact
with the pulp, a superficial layer of tissue necrosis (up to 2 mm) occurs. Underneath
only signs of mild inflammation can be observed.
292 E. Nuni and I. Slutzky-Goldberg

During dentinogenesis growth factors, cytokines and other bioactive molecules

are sequestered in the dentin matrix [69]. These compounds are released as a result
of caries by the bacterial acids [70] and as a result of different rinsing solutions such
as sodium hypochlorite and EDTA (see above). Transforming growth factor beta
(TGF-β) family is one of the main growth factors considered significant in signaling
dentin regeneration. Application of Ca(OH)2 on dentin leads to TGF-β1 release,
thus inducing dentinogenesis [71].
Recent studies in human teeth have found that new odontoblasts or odontoblast-­
like cells can’t be detected histologically after direct pulp capping with Ca(OH)2 or
MTA. Therefore, the nature of the new hard tissue is not clear as it can be dentin or
a dystrophic intra-pulpal mineralization in response to inflammation [72, 73]. The
hard tissue barrier induced by Ca(OH)2 placed on the pulp is porous and contains
tunnel defects [74] (Fig. 17.1).
As Ca(OH)2 is dimensionally unstable and disintegrates slowly over time. These
tunnels can be a pathway for bacterial microleakage leading to pulp damage, dys-
trophic calcification, and eventually necrosis [65].
Hard setting calcium hydroxide cements (e.g., Dycal; Life, Kerr Hawe, Bioggio,
Switzerland) are not recommended for vital pulp therapy. They induce lower pH
and significant weaker antibacterial effect because of the lower release of OH− ions
[75]. They disintegrate with time, do not support the final restoration, induce more
pulp inflammation, and have less hard tissue regeneration [57].
It is also not advised to use light curing Ca(OH)2 (e.g., Ultrablend Plus, Ultradent,
South Jordan, UT; Calcimol LC, VOCO, Cuxhaven, Germany) or calcium-silicate
containing materials (e.g., TheraCal LC, Bisco, Schaumburg, IL) for vital pulp ther-
apy. These materials are cytotoxic and have a significant lower pH [76].

17.3.4 MTA- and Calcium Silicate-Based (CSB)

Materials (Bioceramics)

MTA was presented in the 1990s as the first CSB revolutionary material in dentistry
[77]. It is derived from Portland cement and was indicated initially as a root-end
filling material and with time has been recommended for pulp capping, pulpotomy,
apical barrier formation in immature teeth, and root perforations repair. It consists
of a hydraulic calcium silicate powder that sets in the presence of moisture. When
mixed with water, Ca(OH)2 and calcium silicate are formed causing its high alkaline
pH [78, 79].
MTA is a bioactive material that is commonly used for vital pulp therapy because of
some of its favorable characteristics. Most of the initial studies and recently available
data are based on ProRoot MTA (Tulsa/Dentsply, Tulsa, OK). The material is hard set-
ting and non-soluble. It forms a superior bonding to dentin by the formation of hydroxy-
apatite crystals that create chemical bonding between the MTA and the dentin. As a
result, the material is biocompatible and has an excellent seal. Thus, it provides an
additional protective layer in cases of coronal leakage, unlike Ca(OH)2 [79]. It pos-
sesses some antibacterial and antifungal properties due to its high alkalinity [78].
17 Endodontic Treatment for Young Permanent Teeth 293

The material promotes proliferation, differentiation, and activation of hard

tissue-­forming cells, thus inducing dentin formation and hard tissue repair in several
mechanisms, such as the release of growth factors, cytokines, and bioactive mole-
cules (see Ca(OH)2) from the dentin and fibroblasts [80, 81].
As demonstrated with Ca(OH)2, in an in vivo study of direct pulp capping with
MTA in human teeth, the mineralized tissue formed was mostly atubular and did not
display the features of regular dentin. No odontoblasts or odontoblast-like cells
could be detected histologically [73].
MTA has a few drawbacks, mainly a long setting time (2–4 h), difficult handling
properties, tooth discoloration which was demonstrated by either gray or white
MTA, and difficulty to remove after setting [82]. It was shown that the hard tissue
formation after the use of MTA was superior and caused less pulpal irritation than
Ca(OH)2 [83]. Furthermore, the long-term success after vital pulp therapy using
MTA was better than Ca(OH)2 [84, 85].

17.3.4.1 Biodentine and EndoSequence Root Repair Material

In recent years, a considerable number of new materials based on calcium silicate
(bioceramics) were introduced into the market. It should be emphasized that the
term MTA or bioceramic material is generic, and whereas many papers regarding
several materials such as ProRoot MTA, Biodentine™, or EndoSequence root repair
material were published, there is only limited information regarding some of the
other materials. Therefore, before using a new material, the prudent clinician should
study the current knowledge regarding this material.
These new materials have a few significant advantages in comparison to
MTA. One of the important ones is their better handling characteristics and faster
setting time. Biodentine™ (Septodont, Saint-Maur-des-Fossés, France) is presented
in a form of a capsule containing powder and liquid that is mixed in a triturator. Its
setting time is 12 min [86]. It releases Ca ions forming Ca(OH)2 [87] and TGF-β1
from pulp cells [88] inducing proliferation, migration, and differentiation of human
dental pulp cells [89, 90].
In conclusion, although Ca(OH)2 has many favorable properties, calcium silicate-­
based materials are preferred over Ca(OH)2 for vital pulp therapy. The use of newer
materials instead of ProRoot MTA may be advised considering their improved
characteristics.

17.4 Pulpotomy

Pulpotomy was defined by Finn 1959 as “the removal of a coronal part of pulp tis-
sue followed by placement of a dressing or medicament that will promote healing
and preserve the vitality of the tooth.” Despite many technical changes made since
its introduction by Sweet in 1930, the basic principles of pulpotomy have not
changed [91]. The rationale behind this procedure is the gradual propagation of
bacterial invasion into the pulp tissue.
294 E. Nuni and I. Slutzky-Goldberg

Cvek et al. described in 1978 the pulpal reaction following pulp exposure after
cavity preparation or crown fracture and calcium hydroxide dressing in monkeys.
The depth of inflammatory changes was limited to 2–3 mm [92].
In the early stages of pulp disease and until the pulp becomes completely necrotic,
there is coexistence of healthy and damaged pulp tissue [93, 94]. The coronal por-
tion of the pulp may become necrotic, while the more apical tissue can remain vital,
and only moderately inflamed.
The traditional indications for pulpotomy include the treatment of a carious tooth
or traumatically exposed pulp, to allow preservation of vitality and function of the
remaining pulp [7, 53] (Fig. 17.2). The periapical area appears radiographically
normal, and hemorrhage is controlled. This procedure was limited to teeth which
required only small- or medium-sized restorations [95]. Contraindications include
teeth with spontaneous pain, periapical radiolucency, excessive hemorrhage, puru-
lent or serous exudates, or pulp calcifications [95]. Teeth with interradicular bone
loss or evidence of internal resorption were also excluded.
Initially, only teeth with normal pulp (e.g., iatrogenic exposure) or reversible
pulpitis were treated by pulpotomy. More recently pulpotomy was also indicated for
immature and mature permanent teeth in young adults with symptomatic and
asymptomatic irreversible pulpitis, as well as teeth with periapical radiolucency,
when only part of the pulp was affected [96–99] (Fig. 17.1). Bone resorption occurs
as early as 15 days after pulp exposure and infection, after which the lesion stabi-
lizes [100]. Periapical inflammation precedes total pulp necrosis and is a result of
cytokines and inflammatory mediators extending into the periapical tissue. The
removal of the inflamed pulp during pulpotomy can enable repair of the periapical
lesion [101] (Table 17.1).

a b c d e

Fig. 17.2 Partial pulpotomy with a bioceramic material. (Courtesy: Dr. Iris Slutzky-Goldberg).
(a) A 9-year-old girl was referred for treatment of the left central incisor immediately after a com-
plicated crown fracture. A small pulp exposure was observed. The tooth was sensitive to percus-
sion and highly sensitive to cold application. A periapical radiograph demonstrated an immature
root corresponding to Nolla stage 9. (b) Partial pulpotomy with EndoSequence root repair mate-
rial. A temporary flowable composite restoration was placed on top of the bioceramic material.
(c) 3 months’ follow-up demonstrates a calcified bridge 1 mm apical to the bioceramic material.
The crown had been restored with a composite resin. (d) 6 months’ follow-up—complete root
maturation is evident with partial obliteration of the root canal space. (e) 3-year follow-up—the
asymptomatic tooth during orthodontic treatment. Normal response to cold test was recorded
17 Endodontic Treatment for Young Permanent Teeth 295

Table 17.1 Outcome of pulpotomy carried out with different materials

Material Follow-up
No. of and Ages period Success
Authors teeth procedure Etiology (mean) (month) Diagnosis rate
Taha and 20 Biodentine Caries 9–17 6 months, Irreversible 95%
Abdulkhader Full 1 year pulpitis N = 6
pulpotomy + PA lesion
N = 14
Linsuwanont 55 MTA Caries 7–68 ≤62 months All 87.3%
et al. (29) Immature 100%
teeth
(N = 10)
Irreversible 84%
pulpitis
+ PA lesion 76%
Qudeimat 23 MTA Caries 7.6– 18.9–73.6 78% 100%
et al. Molars Full 20/23 13.6 Irreversible 53%
pulpotomy (10.7) pulpitis and bridge
apical formation
periodontitis

Studies report the outcome of pulpotomy in various pulpal pathologies. The

expected outcomes of the procedure are lack of signs and symptoms, combined with
continued root maturation, dentin bridge formation, and healing of periapical rar-
efaction [97].

17.4.1 Clinical Procedure: Partial and Cervical Pulpotomy

This procedure should be performed only after more conservative treatment options,
such as selective caries removal (previously described as indirect pulp capping, or
direct pulp capping) were ruled out (see Chaps. 10 and 12).
The tooth should be anesthetized prior to the procedure. The type of anesthesia,
either lidocaine and adrenaline or prilocaine without adrenaline, had no effect on
the outcome [102]. The use of intra-pulpal anesthesia should be avoided in order to
prevent damage to the pulp tissue [103]. In a meta-analysis published in 2018, local
infiltration with articaine or lidocaine nerve block for pulpal anesthesia were found
to have similar efficacy in pediatric dentistry, yet less postoperative pain was
reported following articaine. No difference in the occurrence of adverse effects
between the material was reported [104]. After rubber dam isolation, the tooth
should be rinsed with sodium hypochlorite. The use of magnification and illumina-
tion, preferably with the dental operating microscope, is recommended. Following
complete caries removal, or after traumatic crown fracture with pulp exposure,
2 mm of pulp tissue is removed using a new high-speed round diamond bur with
water coolant (Fig. 17.2a). The use of a tungsten or carbide bur is contraindicated as
not to tear the remaining pulp tissue [105]. The cavity and the pulp are rinsed with
296 E. Nuni and I. Slutzky-Goldberg

sodium hypochlorite throughout the procedure. Visualization of the remaining pulp

tissue must be done, as previously mentioned. This is followed by an attempt to stop
the bleeding using a cotton pellet soaked in sodium hypochlorite for 5–10 min with
light pressure. When hemostasis is achieved, a bioceramic material is placed over
the amputated pulp [106, 107] (Fig. 17.3c, d). The use of a biomaterial that can
cause crown discoloration should be avoided. Hence, materials such as Biodentine™
or BC EndoSequence root repair material should be preferred over MTA in esthetic
regions. An immediate permanent restoration, such as glass ionomer or adhesive
restoration, should be preferred [107, 108] (Fig. 17.3e).
Biodentine™, which is used as a capping material, can also fill the access cavity
and serve as a temporary restoration. However, it is not indicated in cases of exten-
sive coronal damage [108]. In a study of 41 patients, Biodentine™ was used during
pulpotomy. In most of the cases, the setting time was longer than claimed by the
manufacturer (12 min) and lasted on average 22 min, and in one of the cases as long
as 45 min [109]. Furthermore, whereas bonding to 12 min matured Biodentine™
was shown to be weak and unsatisfactory, 72 h maturation or a delayed bonding of
2 weeks resulted in increased bond strength and a more clinically acceptable bond
[108]. Placing the overlying definitive resin composite restoration is best delayed
for at least 2 weeks to allow sufficient intrinsic maturation of the Biodentine™ to
tolerate contraction forces from the resin composite [110].

a b c

d e f g

Fig. 17.3 Cervical pulpotomy with a bioceramic material. (Courtesy: Dr. Eyal Nuni). (a) A
7.5-year-old girl was referred for endodontic treatment of the first mandibular molar, due to sec-
ondary caries. The tooth was asymptomatic with a prolonged response to cold test. (b) Following
caries removal and pulp exposure, bleeding and pus secretion were demonstrated. (c) Healthy
looking pulp tissue was observed after cervical pulpotomy and sodium hypochlorite hemostasis.
(d) Pulp capping with EndoSequence root repair material. (e) Fuji IX™ Glass ionomer was placed
on top of the bioceramic material. (f) Post-op radiograph. (g) 13-month follow-up demonstrating
complete root maturation
17 Endodontic Treatment for Young Permanent Teeth 297

If the pulp continues to bleed, a stepwise approach is suggested: deeper amputa-

tion of the pulp tissue should be carried out, until normal-looking tissue is observed.
The same procedure can be repeated, until reaching the canal orifices, thus perform-
ing a cervical pulpotomy (Fig. 17.3).
Nevertheless, in some cases, especially in traumatized teeth with wide canals,
when the pulp in the canal orifices presents signs of inflammation, a deep pulpot-
omy below the root orifices may allow apexogenesis. Leaving vital tissue in the
canal can encourage the continued physiological development and formation of the
root end [53]. However the treatment outcome of this procedure is less predictable
(Fig. 17.1). A meticulous case selection and the use of the operating microscope are
obligatory [58].

17.4.2 Bleeding Time

One study compared the outcome of pulpotomies performed in 14–60-year-old

patients using Biodentine™ in teeth diagnosed as either mild, moderate, or severe
pulpitis according to Wolters classification [54] previously described. The authors
found that the average time for hemostasis ranged from 1 to 4 min. Only a small
difference in bleeding time was found between teeth with mild or moderate pulpitis.
In teeth with severe pulpitis, an average of more than 2 min was required to stop the
bleeding, although the difference between the groups was insignificant. The 1-year
outcome was significantly better for the mild group compared with the severe pul-
pitis group [109].

17.4.3 The Expected Outcome

Successful pulpotomy, either partial or cervical, results in the maintenance of pulpal

vitality. A hard tissue barrier is expected to be apical to the bioceramic material. The
immature root continues to develop, and apexogenesis is usually observed
(Fig. 17.2). The success rate of Ca(OH)2 or MTA pulpotomy in immature teeth is
between 90% [84] and 100% [111, 112], depending on the materials used and the
follow-up period.

17.4.4 Pulpotomy with Different Materials

Different dressing materials such as Ca(OH)2, MTA, and other bioactive materials,
as well as platelet-rich plasma (PRP) and platelet-rich fibrin (PRF), are all used dur-
ing pulpotomy. When MTA and Ca(OH)2 pulpotomies were carried out within the
same patient, the 12-month recall demonstrated 100% success for MTA as com-
pared with 91% for Ca(OH)2 [84]. A comparison of partial pulpotomy with MTA or
Biodentine™ in 69 patients aged 6–18 with signs of irreversible pulpitis showed
298 E. Nuni and I. Slutzky-Goldberg

similar success rates for both materials after a mean follow-up of 32 months (92%
vs. 87% respectively, p ≥ 0.05), although more discoloration was observed in the
MTA group [113]. Similarly, the clinical and radiographic outcome of pulpotomy
with white MTA or Biodentine™ in traumatized anterior immature teeth did not
differ among the 7.5–9 years old patients. However, whereas no discoloration was
observed in the Biodentine™ group at the 6-month follow-up, 23 of the 25 teeth that
were treated with MTA developed coronal discoloration [114]. Comparable success
rates for MTA pulpotomy were reported in another study as well [115]. A study that
compared the effectiveness of three different pulpotomy agents: fast setting MTA
(MM-MTA, Micro-Mega, Besançon Cedex, France), nano-hydroxyapatite (NHA)
and platelet-rich fibrin (PRF) in immature permanent molars did not find a differ-
ence in the treatment outcome among the tested materials. At 12 months, all teeth
demonstrated evidence of continued root maturation, although MM MTA and NHA
had a higher tendency for canal obliteration [116]. Calcific metamorphosis was also
reported following pulpotomy in teeth treated by either Ca(OH)2 (2 out of 15 teeth)
or MTA (4 out of 15 teeth), although not considered a sign of failure [84]. The radio-
graphic outcome of pulpotomies in 60 permanent mandibular molars with signs of
irreversible pulpitis that were treated with a light-cured calcium hydroxide (Dycal;
ApaCal ART, Brussels, Belgium), EndoSequence root repair material, or PRF was
evaluated after 6 months and a year. No statistically significant difference was
observed in the outcomes of the three materials tested. Although clinically after
12 months, PRF and EndoSequence showed the highest reduction of pain mean
score [117]. A meta-analysis published in 2019 compared different pulpotomy-­
dressing agents in the treatment of immature permanent teeth. After the screening of
1365 articles, five randomized clinical trials were included; comparable success
rates were found between the calcium hydroxide, calcium-enriched material (CEM),
PRF, and MTA, even though the authors reported a high risk of bias [118].

17.4.5 Timing of Pulpotomy After Traumatic Injuries

The classic paper published by Cvek et al. in 1982 suggested that pulp amputation
can be carried out within a week after vital pulp exposure due to crown fracture [6].
More recently it was published that a delay of up to 9 days between the time of
trauma and treatment is considered safe [7, 119]. Bimstein and Rothstein also con-
cluded that an exposure size smaller than 4 mm does not affect the outcome of Cvek
pulpotomy [7].

17.4.6 Prognostic Factors

A meta-analysis aimed to assess the prognostic factors affecting the outcome of

partial pulpotomy in carious permanent molars found a success rate of 98% after
6 months, the success rate dropped after 2 years to 92%. The only significant prog-
nostic factor was the preoperative pulp status. The authors stated that neither the
17 Endodontic Treatment for Young Permanent Teeth 299

patient’s age nor apical closure or the pulp capping material affected the treatment
success rate. Indicating that partial pulpotomy can be a viable option for both mature
and immature teeth [120].
Pulpotomy requires less chair time compared to root canal treatment and reduces
the number of radiographs, therefore enabling better patient cooperation. In com-
parison, endodontic treatment, especially in immature teeth, may also require addi-
tional apexification. The simplicity of pulpotomy makes it less technique-sensitive
thus more feasible and less costly than root canal treatment [121].
Restoration of the teeth is an integral part of vital pulp therapy. Long-term evalu-
ation of the effect of the time span between vital pulp therapy and the final restora-
tion shows that a shorter period predicts a better outcome [107].

17.5 Regenerative Endodontics

According to the AAE glossary of terms, these are “Biologically-based procedures

designed to physiologically replace damaged tooth structures, including dentin and
root structures, as well as cells of the pulp-dentin complex” [53]. In the endodontic
literature, regenerative endodontics, revascularization, and revitalization are used
interchangeably, although they describe different histologic outcomes [11].
In 2004 Banchs and Trope proposed a new protocol for revascularization of an
abscessed mandibular premolar, using a triple antibiotic paste dressing. This
included the induction of an intracanal blood clot and placement of an MTA plug on
the blood clot [122]. This protocol was based on a previous study of Nygaard- Ostby
in 1961, who induced bleeding into the root canal space [123]. The antibiotic com-
position used by Banchs and Trope was based on the finding of Hoshino et al. that
studied the susceptibility of bacteria from infected dentin to different compositions
of antibiotics [124]. Iwaya et al. in 2001 were the first group that applied the concept
of revascularization to treat an infected immature permanent tooth with a chronic
apical abscess. They treated the tooth by repeated dressing of the root canal space
with ciprofloxacin and metronidazole. Thirty months after the initiation of the treat-
ment, they demonstrated complete root formation [125].
The currently used protocol is carried out in two steps [122, 126]. The treatment
is indicated for immature teeth with necrotic pulps, with or without a periapical
lesion. An informed consent must be signed prior to the initiation of the treatment.
Other treatment options must be presented, including apexification or extraction of
the tooth. It is compulsory to explain that the outcome of the treatment is not pre-
dictable, and although apical repair is expected in most cases, the exact outcome
may vary [127]. This will be later described in further detail.

17.5.1 Clinical Procedure

The AAE and the ESE published guidelines to regenerative endodontic treatment
[126, 128]. The following procedure is based on these guidelines.
300 E. Nuni and I. Slutzky-Goldberg

17.5.1.1 First Visit

Anesthesia of the tooth is optional, since the tooth is not vital, although patient’s
cooperation must be considered. Following rubber dam isolation, the access cavity
is prepared, and any necrotic pulp tissue is removed from the root canal space. The
canals should be irrigated with 20 mL of sodium hypochlorite 1.5%–3% for 5 min.
Lower concentrations of sodium hypochlorite are advised because it is less cyto-
toxic. It was shown that 6% NaOCl had a negative effect on the differentiation and
survival of the stem cells of the apical papilla (SCAP) [129]. Negative pressure
irrigation or a side-vented needle positioned 1–2 mm above any vital tissues is used
to prevent extrusion of the irrigation solution to the periapical tissues. Mechanical
instrumentation of the walls of the canals should be avoided. Following NaOCl
irrigation, the canals should be irrigated with 20 mL of saline or 17% EDTA for
5 min. The canals are then dried with paper points. Dressing of the root canals can
be done with a slurry of Ca(OH)2 or a triple antibiotic paste (TAP) consisting of
metronidazole, ciprofloxacin, and minocycline (Fig. 17.4). The antibiotics should
be mixed to a final concentration of 1–5 mg/mL, placed apical to the CEJ. The
dressing should be placed at least 1 mm shorter than the canal length as not to injure
any remnants of vital apical tissues. It can be introduced into the canals using a
lentulo spiral or via syringe.
Since the classic composition of the TAP is associated with crown discoloration
[122, 124], caused by the minocycline, a modified antibiotic paste is suggested in
esthetic regions, especially in anterior teeth [130, 131]. Minocycline can be replaced
by another medicament, such as amoxicillin or clindamycin [128]. Alternatively, a
mixture of ciprofloxacin and metronidazole, otherwise termed “double antibiotic
paste” (DAP), can be placed in the canals [128]. A leakproof temporary restoration
should be placed at the completion of this step [126]. The prudent clinician must
verify that there are no known allergies to the antibiotics used.

17.5.1.2 Second Visit

The second appointment is scheduled 1–4 weeks later [126, 128]. If signs or symp-
toms of infection continue, consider repeated dressing of the canal with the same
medicament for additional time or use another antimicrobial agent. The tooth is
anesthetized with 3% mepivacaine without a vasoconstrictor and isolated with a
rubber dam. Then the canals are irrigated with 20 mL of 17% EDTA for 5 min and
dried with paper points. At this point, bleeding is induced by the introduction and
rotation of a pre-bent Hedstrom file beyond the apex and irritation of the periapical
tissue. The canal is allowed to fill with blood up to 2–3 mm below the cemento-­
enamel junction. The formation of a blood clot is expected within 15 min. If neces-
sary, a resorbable collagen matrix (e.g., CollaPlug®, Zimmer Dental, Carlsbad CA)
is placed on top of the blood clot, the matrix should be allowed to soak with the
liquid to avoid the formation of a hollow space.
An intracanal non-staining hydraulic silicate cement, for example, Biodentine™
or EndoSequence root repair material, is placed on top of the matrix in a layer of
17 Endodontic Treatment for Young Permanent Teeth 301

a b

c d

Fig. 17.4 Revascularization with MTA. (Courtesy: Dr. Iris Slutzky-Goldberg). (a) A 6.5-year-old
girl. Carious first mandibular molar. The access cavity is open to the oral cavity. Previous trials to
treat the tooth failed due to poor cooperation. Preoperative demonstrated an immature tooth (Nolla
stage 7) with a large periapical radiolucency. (b) Post-op radiograph—revascularization under
N2O sedation was carried out in two steps: initial dressing with triple antibiotic paste and place-
ment of MTA 4 weeks later on top of the blood clot. (c) 5 years’ follow-up—the tooth was restored
with a stainless-steel crown. Complete healing of the periapical lesion and continued root develop-
ment. Part of the MTA plug in the both roots dissolved with time. Remnants of the MTA can be
seen along the canals. The tooth does not respond to cold tests. (d) 12 years’ follow-up—normal
periapical tissues, continued root development is evident

2–3 mm kept underneath the cemento-enamel junction. The collagen matrix facili-
tates control of the hydraulic cement that is placed coronally.
Finally, the tooth is hermetically sealed with a glass ionomer (e.g., Fuji IX™, GC
America, Alsip, IL) or an adhesive restoration, depending on the type of hydraulic
cement used. As previously mentioned, concerns have been raised regarding the
strength of the bond between Biodentine™ and glass ionomer or composite [110,
132]. We suggest that an alternative temporary filling material will be placed, until
the Biodentine™ has completely set.
302 E. Nuni and I. Slutzky-Goldberg

17.5.2 Scaffold

The early study of Thibodeau et al. demonstrated better treatment outcome after
revascularization in dogs’ teeth when a blood clot was present in the apical portion
of the disinfected root canals [133]. According to Lovelace, the influx of apical
blood into the root canal space was accompanied by an accumulation of undifferen-
tiated mesenchymal stem cells. These cells may promote the regeneration of pulpal
tissues. Although the exact source of these cells is not clear, the apical papilla which
is rich in mesenchymal cells may be the source [134]. However, bleeding into the
root canal space is not always feasible. Several options were suggested to promote
bleeding, including the use of an anesthetic solution without adrenalin, as previ-
ously described. Alternatively, the use of different scaffolds, such as platelet-rich
plasma (PRP) and platelet-rich fibrin (PRF), was suggested in regenerative end-
odontic treatment [135].
The outcome of endodontic regeneration using blood clot induction (BC), PRP,
and PRF in revascularization of immature necrotic teeth was compared 1 year after
completion of the treatment. PRP was better than PRF or BC when the periapical
healing was evaluated. Elongation of the root, thickening of the dentinal walls, and
response to vitality testing was similar among groups [136].
In contrast, the results of revascularization using induced platelet pellet (PP)
without prior apical bleeding, BC, PRP, and PRF were compared in another in vivo
study. The procedure was performed in 88 immature necrotic incisor teeth in chil-
dren aged 8–11. After 28 months’ follow-up, an apical root closure was observed in
73.9% of the teeth, usually in a conical shape, with similar closure rates among
groups. Nevertheless, the radiographic root area, corresponding to the extent of root
development of the BC, was significantly greater than those of the PP and PRF
groups. The radiographic canal area in the BC group was significantly greater in
comparison to the other scaffolds used. Clinically 86% of the teeth were positive to
sensitivity testing [137]. However the use of PRP or PRF requires drawing of blood
from the patient and handling of the blood, thus making the procedure more cum-
bersome, and requires patient’s cooperation which may be problematic especially in
apprehensive children.

17.5.3 Follow-Up

Follow-up is scheduled for 6 months, a year, and then yearly after revascularization
[126, 128].

17.5.4 Expected Outcome

Primary goal: Resolution of the periapical lesion and elimination of symptoms

(Fig. 17.4).
17 Endodontic Treatment for Young Permanent Teeth 303

Secondary goal: Continued root maturation, including an increase of root wall

thickness and elongation of the root. This may occur within 1–2 years after treatment.
Tertiary goal: Positive response to sensibility testing (AAE).
It is noteworthy that the outcome of revascularization is influenced by many fac-
tors, such as patients’ age, apical diameter, the type of dressing material, the scaf-
fold, the capping material, and the follow-up period. Thus, making a comparison
between the different protocols is very difficult, especially with the lack of enough
available data.

17.5.4.1 Healing of Periapical Lesions

Periapical healing after revascularization is expected in most of the cases. The
reported healing rate of periapical lesions in immature teeth is relatively high rang-
ing between 93% [138] and 100% [139, 140].

17.5.4.2 Continued Root Maturation

Ong et al. in a meta-analysis published in 2020 concluded that although root thick-
ening occurred in 90.6% of the cases, lengthening of the root was observed in only
77.3% of the cases, and the incidence of apical closure was 79.1%. However, if a
cutoff point of 20% radiographic change, representing a more significant clinical
change, was used, then regenerative endodontics would have resulted in only 39.8%
root thickening and 16.1% elongation [138].

17.5.4.3 Response to Sensibility Tests

Doubts have been raised as to the positive response of the revascularized teeth to the
application of thermal tests such as Endo Ice and other refrigerating materials or
EPT, especially considering the intracanal MTA or bioceramic barrier. Saoud et al.
reported the successful outcome of revascularization in 20 traumatized immature
permanent necrotic teeth, although none of them regained their responsiveness to
sensibility testing [141].

17.5.5 Survival

High survival rates were reported. A longitudinal cohort study of regenerative end-
odontic treatment of immature necrotic teeth found survival rate of 96.4% [140].
The Mahidol study reported a 100% survival rate [139], whereas a systematic
review and meta-analysis based on three randomized controlled trials, six prospec-
tive cohort studies, and two retrospective cohort studies reported 97.3% survival
[138]. Similar survival rates (96%) were reported by Wikstrom et al. in a systematic
review that included only peer-reviewed studies of at least 20 cases followed for
2 years [142].
304 E. Nuni and I. Slutzky-Goldberg

17.5.6 Pulp Regeneration

Regeneration, which is expected to take place after a revitalization procedure, refers

to the restoration of the original tissue function and architecture. Pulp-like tissue
formation within the root canals is expected where stem cells will differentiate into
odontoblasts capable of secreting tubular dentin [143]. The early study of Thibodeau
in dogs (2007) demonstrated continued root development. Histologic evidence of
hard tissue formation was observed in some of the cases, with new vital tissue in the
canals [133], although these tissues lack the characteristics of a normal dentin-pulp
complex.
There are no human studies regarding the nature of tissue forming in the root
canals. Our knowledge is therefore based on animal studies or case reports. In an
animal model, canines from four ferrets were infected, dressed with TAP, and then
used either BC or PRP as a scaffold. Ingrowth of hard tissue was observed in the
apical part of the root canal [144]. In a study which used dog’s teeth, vital tissue
formed in the canal space of 30 premolars treated by revascularization. The teeth
were treated by either TAP, Propolis, or without any medication. The new tissue
found in the canals had characteristics of cementum and PDL [145]. Saoud et al.
demonstrated that the tissue found in the root canals of Mongrel dogs was cementum-­
like, bone-like, and periodontal ligament-like, and in some cases ingrowth of apical
bone into the root canals was observed [146].
Shimizu et al. in a case report examined the tissue formed in a human immature
permanent tooth after revitalization. The procedure was considered successful, and
continued root maturation was observed. The tooth was extracted 26 months after
treatment because of an unrestorable horizontal crown fracture. The histologic
examination revealed well-mineralized cementum- or bone-like tissue [147].
Becerra et al. examined the tissue formed after revascularization in a tooth that was
extracted because of orthodontic reasons. The radiographic examination showed
resolution of the apical radiolucency and narrowing of the root apex. The histologic
examination demonstrated soft connective tissue similar to that in the periodontal
ligament and cementum-like or bone-like hard tissue [148]. Martin et al. examined
the histologic characteristics of a fractured extracted molar 2 years after revascular-
ization using PRF. They could not find any pulp-like tissue or the presence of polar-
ized odontoblasts along the dentin. The irregular mineralized tissue formed in the
distal and mesial canals was cementum-like with an uninflamed fibrous connective
tissue that could be followed up to the MTA plug [149].
Based on the currently available data, it can be concluded that true pulp-dentin
complex regeneration does not occur as a result of this treatment. Therefore, a more
appropriate way to describe the outcome of the procedure is revitalization or
revascularization.
17 Endodontic Treatment for Young Permanent Teeth 305

17.5.7 Tissue Reactions

Chen et al. described the outcome of revascularization in 20 immature necrotic per-

manent human teeth diagnosed with either apical periodontitis or apical abscess
[127]. The patients were followed up from 6 to 26 months. Although ideally contin-
ued root maturation and apical root closure is expected after revascularization,
described as type 1, this result is not predictable. Four additional types of radio-
graphic responses to the revascularization procedures were also observed: type 2,
the root apex becoming blunt and closed, without any significant continuation of
root development; type 3, continued root development, although the apical foramen
remains open; type 4, severe pulp canal obliteration (Fig. 17.4); and type 5, a hard
tissue barrier formed in the canal apical to the coronal MTA plug [127]. Chan et al.
followed 28 teeth after revascularization for 30 months. According to their study,
complete apical closure was radiographically observed in only 30.8% [140]. Fida
et al. reported radiographic evidence of bone ingrowth into the root canal space in
three cases. The bone was surrounded by normal PDL without ankylosis [150].

17.5.8 Influence of Apical Diameter on the Outcome

of Revascularization

An apical foramen size of 1.1 mm was thought to be necessary for successful revas-
cularization [151]. However successful revascularization cases were observed even
when the diameter was as small as 0.5 mm. A study compared the outcome among
two age groups: children aged 9–13 and 13–18. The authors found that after a
12-month follow-up period, the younger group showed significant increase in root
length and width of the canal walls (Fig. 17.4). However, in the group of children
aged between 13 and 18, a wider diameter (larger than 1 mm) resulted in greater
increase in root length and thickness. They stated that the preoperative apical diam-
eter is a strong predictor for the outcome of the procedure [152]. The longitudinal
study by Chan et al. [140] previously described concluded that teeth with more
immature stages of root development had a higher percentage of change in root
thickness, length, and apical diameter. The authors of the study used a triple antibi-
otic mixture, consisting of cefaclor, ciprofloxacin, and metronidazole. Furthermore,
this change was more evident in teeth with less than half of the root length formed
than in teeth with the root almost completed with an open apex (Nolla stage 9) [153].
Considering the data presented, we suggest that the less developed the root, the
more advantageous a revitalization would be. Alternatively, root canal treatment
including apexification (apical plug) can be considered for the treatment of teeth
with an open apex with an inflamed or necrotic pulp. This will be discussed later in
this chapter.
306 E. Nuni and I. Slutzky-Goldberg

17.5.9 Comparison of Revascularization and Apexification

The Mahidol study compared the outcome of calcium hydroxide apexification,

MTA apexification, and revascularization in immature necrotic teeth. The survival
rate of revascularization (100%) was similar to MTA apexification (95%) but sig-
nificantly higher than calcium hydroxide apexification (77%). The study also dem-
onstrated similar success rates for the three treatment modalities [139].
A meta-analysis published in 2019 showed no statistical difference between the
overall clinical and radiographic outcome of revascularization using blood clot
induction or MTA apexification. Similar survival rates were also reported. The
authors reviewed 231 papers although only four papers were included [154].
Wikstrom et al. in 2021 evaluated in a systematic review the survival, success, and
root development after regenerative endodontics or MTA apexification of immature
necrotic teeth. According to their review, both treatments were effective and had
equal success and survival rates. However, endodontic regenerative techniques were
superior to apexification in terms of continued root development [142].
Based on the data presented, we recommend that revascularization/revitalization
will be performed in immature necrotic teeth with an early stage of root develop-
ment. Teeth with an apical diameter larger than 1 mm are good candidates for this
procedure in all age groups. Revascularization offers a potential for root elongation
and thickening of the canal walls and is more effective in less mature teeth. Over
time it is, therefore, more advantageous in teeth with unfavorable crown:root ratio.
Furthermore, if revascularization fails, a second option for a conservative root
apexification is available [154]. On the other hand, if the root has almost reached its
full development, apexification and root filling have a more predictable outcome. It
should be emphasized that although revascularization enables root apexogenesis, it
has no effect on strengthening the peri-cervical area which is more prone to frac-
tures in young permanent teeth.

17.6 Root Canal Treatment in Young Permanent Teeth

and Apexification

Root canal treatment in young permanent teeth should be the last option for treat-
ment and performed only when other vital pulp treatment options are not possible
or when the diagnosis of pulp necrosis is conclusive [119].
It should be noted that in many cases root canal treatment may be much more
complicated than initially thought, because of the specific characteristics of these
teeth and the cooperation of the young patient. Vital pulp therapy is easier to per-
form, more conservative, and more cost-effective [155] (Fig. 17.4a).
Dental caries and traumatic injuries are the most common problems leading to
pulp necrosis in children with young permanent teeth [53]. In the carious tooth, the
immune responses develop as the lesion advances, leading to increased inflamma-
tion, edema, and pain. Eventually, the inflammation in the low compliance environ-
ment of the pulp space will cause pulp disintegration and apical pathosis [156].
17 Endodontic Treatment for Young Permanent Teeth 307

The development of the root is completed approximately 3 years after eruption

[1]. The root morphology and the degree of apical closure vary in accordance with
the stage of root development. Root canal treatment in immature young permanent
teeth creates distinct problems in disinfection, obturation, and badly broken-down
teeth also in restoration. Thinner canal walls and more immature and wider apical
foramen make the treatment more challenging. These teeth are also more suscepti-
ble to root fracture after treatment [11, 157].
In a retrospective cohort study published in 2021, the estimated 5-year survival
rate of 424 endodontically treated teeth was 80% for 15–18-year-olds, 64.8% for
12–14-year-olds, and 46.4% for 6–11-year-olds. In the total study sample, the esti-
mated cumulative survival probability was 69.1% at 5 years. The authors concluded
that endodontically treated teeth are more likely to survive when the treatments are
performed at an older age [158].

17.6.1 Clinical Procedure

Conventional root canal treatment includes access preparation, cleaning, shaping,

disinfection (chemical and mechanical preparation), and obturation of the canal sys-
tem followed by restoration of the treated crown [128].
Before treatment, a careful radiographic evaluation of the roots and pulpal anat-
omy is indicated, using one or two radiographs from different horizontal angles.
The use of a vertical bitewing radiograph can allow visualization of the extent of
carious damage, the furcation area, and the height of marginal bone. In young chil-
dren with shorter roots, it can also demonstrate the periapical area, making a second
periapical radiograph unnecessary.
The use of CBCT may be essential in complex cases [50, 159] (see radiographic
examination). The use of magnification (preferably a dental operating microscope)
and illumination during the treatment is recommended.

17.6.1.1 Access Preparation

Following anesthesia, the tooth is isolated with a rubber dam. This may be extremely
challenging in the erupting tooth. Several options are suggested: including the
placement of the clamp on a posterior tooth, gingivectomy to expose the cervical
region, use of a serrated clamp, or placement of the sterile clamp on the gums. When
there is a risk of complex anatomy (e.g., dense invaginatus, calcifications, etc.) of
the tooth, rubber dam placement can be postponed after the initial or complete
access preparation.
Before entering the pulp chamber, all caries should be removed and preferably
all present crown restorations. During access preparation, the entire roof of the pulp
chamber and all coronal pulp tissue (vital or necrotic) is completely removed; spe-
cial care must be taken to any pulp tissue in the pulp horns. Sound tooth structure
should be conserved as much as possible.
The pulp chamber is rinsed throughout the preparation with NaOCl, and all the
canal orifices are located [160].
308 E. Nuni and I. Slutzky-Goldberg

17.6.1.2 Mechanical and Chemical Preparation

The mechanical and chemical preparation is aimed to disinfect the canal system to
prevent any periapical disease or promote healing and repair of the peri-radicular
tissues [128]. The mechanical preparation objectives are to remove infected hard
and soft tissue, allow access to disinfecting irrigants to the entire canal space, and
create space for the delivery of medicaments and obturation materials while retain-
ing the integrity of radicular structures [160]. After locating the canal orifices, the
canal length is estimated with a parallel preoperative radiograph. The canal length
is measured using an electronic apex locator (EAL) and confirmed with a radio-
graph. It should be taken into consideration that EAL measurement can be inaccu-
rate in canals with open apices.
In these cases, final confirmation using paper points is possible. The paper point
is inserted briefly 2 mm short of the approximated canal length and after withdrawal
inspected for moisture at the tip. When the tip is dry, this action is repeated in incre-
ments, each time 0.5 mm longer. The working length is at the point in which mois-
ture is present [161].
The mechanical preparation includes the use of hand and rotary nickel-titanium
(NiTi) files. In immature teeth with wide or blunderbuss canals, this preparation is
not effective as the files will not contact the entire canal walls. In narrower canals,
rotary NiTi files are recommended, as they better follow the original morphology of
the canals and reduce preparation errors [160]. Filing should be cautious because it
can endanger the thin dentinal walls. Additionally, the use of non-standardized files,
such as XP finisher (FKG, Switzerland) or SAF (ReDentNova, Israel), can aid in the
preparation of the wide canals.
During the mechanical preparation, the canal is irrigated with a disinfecting irri-
gation solution. The most common solution is NaOCl because of its antimicrobial
and tissue (necrotic and vital) dissolving properties (see Sect. 17.3).
Care should be taken not to extrude the solution beyond the wide apical foramen.
Therefore, in young permanent teeth, the use of a lower concentration of NaOCl
should be considered. Copious amounts of irrigation solution should be used to
compensate for the low concentration [162]. Irrigation needle with a blunt end and
side vented holes should be placed passively 1 mm short of the canal length [163].
Passive ultrasonic irrigation can also be useful in the canals of immature teeth [164,
165]. The use of negative pressure irrigation system, e.g., EndoVac (Discus Dental,
Culver City, CA) is recommended for effective and safe irrigation [166].
Ethylenediaminetetraacetic acid (EDTA) is a chelating agent and can be used in
a concentration of 17% to irrigate the canal before final rinsing with NaOCl to
remove the smear layer [167] (see Sect. 17.3).
The use of 2% chlorhexidine (CHX) instead of, or in combination with, NaOCl is
also possible as it has lower cytotoxicity. Nevertheless, although the materials have
the same antimicrobial properties, CHX has no tissue-dissolving properties [55].
When the root canal treatment cannot be completed in one appointment, Ca(OH)2
is used as an intracanal medication. Although recent studies suggest that there is no
difference in the outcome of root canal treatment in one versus multiple visits [168],
dressing the canals in immature permanent teeth with Ca(OH)2 can be beneficial, as
17 Endodontic Treatment for Young Permanent Teeth 309

the removal of tissue remnants and disinfection can be compromised especially in

very young roots [169]. When the canal preparation is complete, a lentulo spiral is
used to deliver a creamy mix of Ca(OH)2 into the canal. The canal is medicated for
at least 1 week for additional disinfection [170].

17.6.1.3 Root Canal Obturation

Obturation of the canal system is performed after disinfection is completed. In
young permanent teeth filling, the root canal can be difficult as the open apex pro-
vides no barrier for the root filling material. Moreover, the canals are usually diver-
gent, and the apical diameter of the canal is larger than the coronal diameter, thus
compromising the control of the obturation material in the apical area. Furthermore,
forces applied on walls in some obturation techniques can endanger their integrity
and lead to fractures [11]. Following rubber dam isolation, the canals are irrigated
with 17% EDTA to remove the Ca(OH)2 and then irrigated with NaOCl. The canals
are then dried with paper points and the appropriate obturation technique should be
chosen according to the apical morphology.

Root Canal Apexification in Immature Roots: Apical Barrier Technique

At this point, an exact assessment of the size of the apical foramen and the shape of
the apical portion of the canal is made. Traditionally, apexification was performed
in roots with a wide or divergent apex. This included the placement of long-term
calcium hydroxide dressing in the canals to induce a calcified barrier formation
[171]. The time required for apical barrier formation may be as long as 6–24 months
[65] and requires the patient’s compliance. Furthermore, dressing the tooth with
Ca(OH)2 for a long period is associated with a decrease in fracture strength of
immature roots [172]. In another study, dressing dentin with Ca(OH)2 for 30 days
reduced the compressive strength of dentin, irrespective of the vehicle use: normal
saline, distilled water, or a local anesthetic solution [173].
A simple and less time-consuming procedure is the apical barrier technique,
which involves the placement of a barrier at the apical region to prevent extrusion of
filling material (AAE 2019). This can be done by placing a minimum layer of
3–4 mm of MTA or a bioceramic material at the apical foramen [11], 1 mm short of
the radiographic apex (Fig. 17.5b). Introducing a resorbable collagen matrix (e.g.,
CollaPlug®, Zimmer Dental, Carlsbad, CA) apical to the MTA or bioceramic mate-
rial can aid in controlling the material [174]. In our opinion, materials having putty
consistency (e.g., Biodentine or EndoSequence root repair material) are more user-­
friendly. The remaining space of the canal is filled in the next step using gutta-­
percha and a sealer (see below) (Fig. 17.5c).

Obturation of Mature Roots with Open Apices

An endodontic sealer is introduced into the dry canals. A gutta-percha master cone
fitted to the working length is placed in the canal and the canal is obturated using
lateral condensation, warm obturation, or a combined technique. The use of warm
GP should be avoided when there is a risk of extrusion of the obturation materials
beyond the apical foramen, thus irritating the periapical tissues.
310 E. Nuni and I. Slutzky-Goldberg

a b c d

Fig. 17.5 One visit apexification and root canal treatment. (Courtesy: Dr. Iris Slutzky-Goldberg).
(a) An 8.5-year-old girl. Left central incisor 3 weeks after extrusion and splinting. Negative
response to sensibility testing and stage II mobility (despite the splint). No pain was present during
test cavity preparation, which revealed a necrotic pulp. Since the root was almost fully developed,
root canal treatment was initiated. (b) A 3 mm apical barrier with EndoSequence root repair mate-
rial. Due to increased mobility, a splint was left in situ. (c) Root canal obturation with gutta-percha
and AH plus root canal sealer. The splint was removed after the procedure. (d) 4 years’ follow-
­up—the tooth presents no signs or symptoms. The lateral incisor was treated due to the diagnosis
of apical periodontitis

In wide canals, the canal can be obturated using the chloroform dip technique.
This technique enables better control and adaptation of the cone to the shape of the
apical portion of the canal and therefore simplifies the obturation process. The use
of chloroform has been gradually minimized due to concerns as to its toxicity and
carcinogenicity and replaced by other solvents (e.g., eucalyptol) A master gutta-­
percha point is fitted with friction resistance few millimeters short of the working
length. The tip of the cone is dipped in the solvent or heated for 1–2 s to soften only
the outer superficial layer of the gutta-percha. The softened cone is inserted repeat-
edly into the canal until the cone reaches the working length and an impression of
the apical portion of the canal is obtained. The position and fitness of the cone are
verified with a radiograph [175]. The canal is then obturated using a sealer and the
customized cone in the chosen obturation technique.
The use of recently introduced calcium silicate-based sealers can be considered
in root canal obturation of immature permanent teeth. The properties of some of
these sealers have been published and reported to be similar to MTA. They are con-
sidered bioactive (promoting cell proliferation and adhesion, stimulate hard tissue
formation), biocompatible, and hydrophilic [176]. A recent review states that their
main advantage is their bioactivity and their ability to stimulate hard tissue forma-
tion [177]. However, more investigation of these materials is recommended, and the
clinician is advised to review the research published in the endodontic literature.
The calcium silicate-based sealer is delivered into the canals system by a lentulo
spiral, a special flexible plastic tip, or the gutta-percha master (primary) cone. A
single fitted master cone is then inserted into the canal; additional compaction is not
mandatory. This technique allows adaptation of the sealer to the irregular canal,
enables better control of the obturation material at the working length, and does not
risk the thin canal walls, as no forces are applied during the obturation.
17 Endodontic Treatment for Young Permanent Teeth 311

17.6.1.4 Coronal Restoration

The restoration of the crown of an endodontically treated tooth is of utmost impor-
tance. An adequate root canal treatment and adequate crown restoration will increase
the probability of healing of apical periodontitis [178]. Coronal restoration should
restore the tooth’s esthetic and function while protecting the residual tooth struc-
ture, especially in immature permanent teeth that are prone to fracture [11]. The
European Society of Endodontology (ESE) published in 2021 a position statement
regarding the restoration of root-filled teeth [179]. It recommends that premolars
and molars should be restored with cuspal coverage restorations when at least one
proximal wall is missing while retaining as much sound tooth structure as possible.
This type of restoration is also indicated when a crack is visible. Anterior immature
endodontically treated teeth have thin dentinal walls that are more susceptible to
fracture especially in the cervical area (particularly as a result of trauma) [180]. In
these cases, an intra-coronal bonded restoration is recommended after the removal
of the root filling material below the marginal bone level in an attempt to reinforce
the tooth structure [181, 182].
In anterior and premolar teeth “passive” post placement is beneficial when no
remaining coronal dentin walls are present. In order to preserve sound tooth struc-
ture, an endocrown can be considered as an appropriate alternative to conventional
full-coverage stainless-steel crown [183] (details in Chap. 18).

17.6.1.5 Follow-Up
Follow-up appointments should be scheduled regularly to assess the treatment out-
come. Clinically no adverse signs and symptoms are detected, and the crown is
sealed with a good restoration that does not allow coronal leakage. Radiographic
evidence of resolution of periapical pretreatment periodontitis or normal periapical
tissue is observed with no additional breakdown of the periodontal supporting tis-
sues [119].

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Restoring the Endodontically Treated
Young Permanent Tooth 18
Zafer C. Çehreli

Contents
18.1 Introduction 323
18.2 The Access Cavity 324
18.3 Intraorifice Barrier 325
18.4 Coronal Restoration of Endodontically Treated Young Permanent Teeth 326
18.4.1 Young Permanent Molars 326
18.4.2 Young Permanent Incisors 328
 eferences
R 329

18.1 Introduction

A young permanent tooth may occasionally require vital or nonvital endodontic

therapy as a consequence of dental caries or trauma. For decades, it was believed
that the effectiveness of root canal treatment was influenced by the technical quality
of the root filling [1]. Today, there appears to be ample evidence that the success of
endodontic therapy is equally [2] or even more affected [3–5] by the quality of the
coronal restoration than the technical quality of the endodontic therapy itself. Thus,
it is important for the pediatric dentist to know that in addition to restoring the func-
tion and esthetics, a post-endodontic restoration should safeguard the endodonti-
cally compromised tooth by preventing coronal microleakage and minimizing oral
fluid and bacterial leakage into the periradicular space. Based on limited evidence,
the best way to restore a tooth after endodontic treatment remains a controversial
topic for young permanent teeth. This chapter will review conventional and emerg-
ing treatment options for the restoration of endodontically treated young permanent
teeth along with the factors associated with the long-term survival.

Z. C. Çehreli (*)
Department of Pediatric Dentistry, Hacettepe University, Ankara, Turkey

© The Author(s), under exclusive license to Springer Nature Switzerland AG 2023 323
A. B. Fuks et al. (eds.), Contemporary Endodontics for Children and
Adolescents, https://doi.org/10.1007/978-3-031-23980-9_18
324 Z. C. Çehreli

18.2 The Access Cavity

The endodontic treatment of immature permanent teeth with necrotic pulps involves
little to no mechanical instrumentation so as to preserve the existing thin root walls.
Instead, the root canal is thoroughly disinfected in a non-instrumental fashion by
using large amounts of sodium hypochlorite (NaOCl) with a long contact time.
NaOCl, the most effective antibacterial irrigant in endodontics, has a low molecular
weight along with the ability to penetrate both the dentinal tubules and the intricate
morphology of the root canal system, making it more effective than any endodontic
metal instrument at removing the infected material. It could even be argued that the
new root canal tool in endodontics is a liquid—not metal—which just so happens to
be NaOCl, thanks to recent advancements in active and closed irrigation systems
using exclusively NaOCl and our long-term learning experience from the non-­
instrumental root canal disinfection procedures of regenerative endodontics. It is
crucial to understand that each and every infected dentinal tubule is a root canal
system in and of itself and that the treatment of infected dentinal tubules necessi-
tates the use of liquids and flowable materials for everything from cleaning to
sealing.
Because NaOCl selectively removes the organic component of dentin, particu-
larly type I collagen which is necessary for micromechanical retention of dentin
bonding agents, exposing the pulp chamber to extended contact with NaOCl might
have a negative impact on the effectiveness of resin adhesion [6]. Removal of the
superficial collagen network by NaOCl also weakens the mechanical and structural
properties of dentin [7], leading to decreased fracture strength [8], which might
pose a serious concern in an already fracture-prone immature permanent tooth. This
potential problem can be managed practically by avoiding high concentrations of
NaOCl for irrigation [8].
Always and unavoidably, endodontic sealers contaminate the endodontic access
cavity. While there is currently no method that can entirely remove sealer residue
from cavity walls, traditional alcohol cleaning still appears to be the most efficient
and practical way to remove sealers to the best extent, compared to bur cleaning or
particle abrasion [9], with no additional benefit of combining the latter two methods
with alcohol cleaning. The European Society of Endodontology recommends clean-
ing of the cavity walls with a diamond bur or air abrasion with aluminum oxide to
remove the MTA or tri-calcium silicate cement contamination on access cavity
walls [10].
Ideally, the endodontic access cavity and the crown should be restored at the
same visit with root canal filling. In the case of an indirect restoration requiring
multiple visits, the endodontic access cavity and surrounding restoration margins/
surfaces must be adhesively sealed immediately after root canal obturation, before
impression taking. Delaying the coronal restoration with a temporary material for
extended periods increases the likelihood of recontamination of the root system as
well as risk of future fracture.
18 Restoring the Endodontically Treated Young Permanent Tooth 325

18.3 Intraorifice Barrier

In order to decrease coronal microleakage in root-filled teeth, the intraorifice barrier

concept has been proposed [11]. This simple-yet-effective procedure involves
replacing 3 mm of gutta-percha at the orifice of the root canal with a restorative
material (Fig. 18.1). Numerous investigations have shown the positive impact of
intracoronal barriers in successfully preventing or reducing coronal microleakage,
depending on the material used [12, 13]. More recently, it was demonstrated that
root-filled teeth with an intraorifice barrier are more resistant to post-endodontic
root fractures than those without one [14]. Thus, routine placement of intraorifice
barriers may be a useful reinforcement in young permanent incisors that have under-
gone endodontic treatment when full coverage restorations with the known ability
to reduce root fractures cannot be used. Bonded resin composites, resin-modified
glass ionomer cements, and fiber-reinforced composites are commonly used as
intraorifice barriers. In vitro testing has shown that calcium silicate-based materials
employed as coronal barriers in regenerative endodontic procedures also function as
intraorifice barriers and have a significant sealing and strengthening effect [14].

Fig. 18.1 Radiographic view of a resin-modified glass ionomer intraorifice barrier placed over a
root canal filling with mineral trioxide aggregate apical barrier in a young permanent incisor
(arrow). (Courtesy of Dr. H. Simsek & Dr. Z. Cehreli)
326 Z. C. Çehreli

18.4 Coronal Restoration of Endodontically Treated Young

Permanent Teeth

Endodontically treated teeth undergo a number of irreversible structural changes,

including dentinal dehydration, changes in dentin collagen composition, and a
reduction in micro-hardness, which all may be linked to the risk of future fracture
[15]. When combined with extensive tooth structure loss, root-filled teeth typically
need massive partial or full coverage restorations to sustain the remaining tooth
structure. The evidence base for the restoration of posterior teeth indicates that mod-
ern indirect procedures such as onlays and endocrowns are as predictable as full
coverage crowns.

18.4.1 Young Permanent Molars

18.4.1.1 Prefabricated Crowns

Prefabricated permanent molar crowns (also referred to as adult stainless-steel
crowns) have an overall success rate of almost 90% and an average longevity of
about 45 months across all age categories, with particularly good results in patients
under the age of 9 [16]. The American Academy of Pediatric Dentistry recommends
using adult prefabricated crowns as a semi-permanent restorative option for the
management of immature permanent molars with severe enamel defects or consid-
erable carious tissue loss [17]. When esthetics is not an issue, permanent molar steel
crowns may be the most reasonable, cost-effective restorative option in endodonti-
cally treated, severely broken-down young permanent molars. In molars with a
smaller crown size, oversized primary stainless-steel crowns may be utilized as an
alternative to permanent molar crowns. Adult preformed crowns do not replace the
need for permanent restorations in the future.
There is currently no clinical evidence to support the long-term effectiveness of
newly introduced permanent molar zirconia crowns. Based on the literature from
primary zirconia crowns, the American Academy of Pediatric Dentistry [17] has
reported that the use of zirconia crowns may be associated with better gingival
health than stainless-steel crowns [18] (Fig. 18.2).

18.4.1.2 Indirect Restorations

Today, there is convincing evidence that molars and premolars with sufficient depth
and form within the pulp chamber for core retention can be safely restored without
the use of post systems [19]. Endocrown, a minimally invasive restorative treatment
option, has been utilized effectively in the adult population as an alternative to the
standard post and core technique for over two decades [20]. Endocrown can be
defined as a monoblock adhesive restoration that consists of a crown and pulpal
extension that is bonded to the pulp chamber and cavity margins of an endodonti-
cally treated tooth. Because post space and ferrule are preparation that are elimi-
nated with the use of endocrowns, the remaining tooth structure can be preserved.
Along with the advances in the computer-aided design and manufacturing
18 Restoring the Endodontically Treated Young Permanent Tooth 327

Fig. 18.2 Visible plaque accumulation and marginal gingival view of adult stainless-steel crown
and zirconia crown in the root-filled molars of the same patient after 18 months of clinical use.
(Courtesy of Dr. Z. Cehreli)

a b c

Fig. 18.3 (a) Postoperative radiographic view of a structurally compromised, MIH-affected per-
manent first molar after cervical pulpotomy with a calcium silicate-based material. (b) Placement
of the lithium disilicate CAD/CAM endocrown under strict isolation. (c) 2-year follow-up, demon-
strating complete root development in the absence of periapical pathosis. (Courtesy of Dr. E. Nuni,
Dr. E. Davidovich)

(CAD-CAM) process and resin composite materials, the use of CAD-CAM endo-
crowns in young permanent teeth has become a viable esthetic alternative to adult
stainless-steel crowns (Fig. 18.3). The CAD-CAM technique uses intraoral scan-
ners to obtain digital impressions, which offers a distinct benefit over the difficult
traditional impression taking method in youngsters with poor cooperation [21].
Endocrowns have shown good long-term survival rates in adult molars and premo-
lars, with considerably less catastrophic failures than post and post-and-core
retained coronal restorations [20].
Onlays are another viable esthetic restorative option in root-filled young perma-
nent molars with reduced cuspal support due to extensive carious tissue loss [22].
328 Z. C. Çehreli

Onlays, like endocrowns, can be produced from resin composite blocks using a
CAD-CAM process, saving chairside time and improving patient compliance.
Onlays have shown superior mid-term survival rates in primary molars than
stainless-­steel crowns [22].

18.4.2 Young Permanent Incisors

Direct, light-cured resin composites should be used for the post-endodontic restora-
tion of young permanent incisors with merely an endodontic access cavity. Because
of the presence of surrounding enamel margins, such bonded restorations have
excellent long-term sealing capacity and are rarely subjected to masticatory stresses
that may cause catastrophic failures.
Based on the traditional approach, it may be assumed that endodontically treated
incisors with moderate to extensive tissue loss should ideally be restored with posts
to provide retention for the coronal restoration. Indeed, severely compromised
immature permanent incisors with large, flared root canals can be practically
restored with adhesively luted bundled glass fibers or a combination of bundled
glass fibers and conventional solid glass fiber posts to conform to the irregularly
shaped canal space [23]. However, in the event of a mesial or mesial and distal class
III cavity, as well as an endodontic access cavity, direct resin composite restoration
of the root-filled crown has demonstrated to have comparable fracture strength to
those restored using bundled and solid post systems [24]. There is even growing
evidence that glass fiber posts may not necessarily provide better fracture resistance
than a simple, bonded direct composite core buildup, when sufficient coronal dentin
(ferrule) is available as an intrinsic reinforcement to the core [25–27] (Fig. 18.4).
More importantly, the use of a fiber post cannot compensate for the absence of a
ferrule [26]. Thus, in endodontically treated young permanent incisors, it seems
reasonable to follow the no-post approach performed by the use of bonded direct
composite build-up, so as to decrease the likelihood of unrestorable failures.
18 Restoring the Endodontically Treated Young Permanent Tooth 329

Fig. 18.4 No-post approach in a severe crown fracture. (a) Preoperative radiographic view, fol-
lowed by crown lengthening with ceramic bur and endodontic treatment under isolation. (b) Root
canal filling with final coronal restoration made by bonded direct composite buildup. (Courtesy of
Dr. Z. Cehreli)

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Elucidating Tooth Development
and Pulp Biology by Single-Cell 19
Sequencing Technology

Jimmy K. Hu and Amnon Sharir

Contents
19.1 Introduction 333
19.1.1 Clinical Relevance, Challenges, and Questions 334
19.1.2 Tooth and Pulp Development 335
19.1.3 Basic Principles of scRNA-Seq 337
19.2 Formation and Patterning of the Ectomesenchyme 343
19.3 Odontogenesis from Bud to Bell Stages 345
19.4 Post-Eruption and Adult Stages 348
19.5 Summary 349
References 350

19.1 Introduction

This chapter discusses recent advances in using single-cell transcriptomic technol-

ogy to study tooth development and pulp biology. While the tooth is a mineralized
organ, its vitality and function are supported by soft tissues, such as the periodontal
tissues and the dental pulp [1, 2]. These tissues contain diverse cell populations that
are progressively formed during embryonic development. Decades of research have

J. K. Hu (*)
School of Dentistry, University of California Los Angeles, Los Angeles, CA, USA
Molecular Biology Institute, University of California Los Angeles, Los Angeles, CA, USA
e-mail: [email protected]
A. Sharir (*)
Faculty of Dental Medicine, The Institute of Biomedical and Oral Research, Hebrew
University of Jerusalem, Jerusalem, Israel
e-mail: [email protected]

© The Author(s), under exclusive license to Springer Nature Switzerland AG 2023 333
A. B. Fuks et al. (eds.), Contemporary Endodontics for Children and
Adolescents, https://doi.org/10.1007/978-3-031-23980-9_19
334 J. K. Hu and A. Sharir

revealed the major cell types that comprise the dental pulp, as well as of some of the
genetic and signaling pathways that govern its development and maintenance. These
efforts paved the way for research that aims to utilize dental pulp cells as a source
of stem cells in regenerative medicine [3].
To identify marker genes for each cell type in the dental pulp, decipher the cel-
lular hierarchy, and decode the functions of identified genes and pathways, early
experimental approaches examined dental cell populations in bulk. However, the
lack of cellular resolution has limited our capacity to deconstruct the heterogeneity
within each cell type and the regulatory interactions between subpopulations during
development and regeneration. The advent of single-cell transcriptomic technology
has truly revolutionized biological studies and, particularly, dental research. This
approach allows interrogation of gene expression in each cell of a complex tissue
and, thereby, the discovery of inherent cell lineages, interactions, and transcrip-
tional controls. In this chapter, we present recent benchmark single-cell studies that
addressed key questions in tooth development and highlight findings that advance
our understanding of how the dental pulp forms and functions.

19.1.1 Clinical Relevance, Challenges, and Questions

The dental pulp is the inner soft tissue of the tooth that is surrounded by the hard
mineralized structures of enamel and dentin. Composed of connective tissues, vas-
culatures, immune cells, nerves, and the dentin-producing odontoblasts, the dental
pulp plays indispensable roles in tooth homeostasis and is thereby essential for the
vitality of the tooth. Although protected externally, the dental pulp can incur injuries
and inflammations due to trauma, tooth decay, and cavities. Having only a limited
capacity for self-repair, the standard treatment of pulp diseases often involves root
canal therapy, where soft tissues are removed and then replaced by inorganic mate-
rials. This, however, deprives the tooth from natural blood and nervous supplies,
hence making the tooth susceptible to structural failures and re-infections [4]. By
contrast, regenerative strategies using mesenchymal stem cells (MSCs) or dental
pulp stem cells (DPSCs) hold promise to restore the natural biological functions of
the dental pulp.
Despite promising advances in stem cell-based pulp regeneration in both pre-
clinical and clinical settings, applications of these strategies remain limited in den-
tistry today [5, 6] due to several translational hurdles. First, we lack reliable markers
for the numerous sub-populations of the heterogeneous pulp tissue, as well as suf-
ficient knowledge about the differentiation potential of each sub-population. This
has hindered the efforts to isolate the correct populations for specific clinical appli-
cations. Second, our understanding of the genetic and signaling mechanisms that
control the differentiation processes during pulp development are limited. Therefore,
it is currently challenging to control the proliferation and differentiation of dental
pulp stem cells toward a desired fate, let alone to produce the different lineages that
will reconstruct the cellular compositions and architecture of pulp. Lastly, there is
19 Elucidating Tooth Development and Pulp Biology by Single-Cell Sequencing… 335

little knowledge about the signals required to maintain stem cell survival and func-
tion in teeth or in the engineered niche after transplantation.
In recent years, single-cell RNA sequencing (scRNA-seq) studies have begun to
address some of these issues by providing insights into the complexity of cellular
compositions in the developing pulp and by uncovering the dynamic differentiation
processes through which dental progenitors give rise to diverse tooth cell types.
These studies also revealed key gene regulatory networks that drive the specifica-
tion of each cell type, as well as the dominant signaling interactions that contribute
to the regulation of pulp development.

19.1.2 Tooth and Pulp Development

Chapter 1 explains in detail the developmental processes of tooth and pulp forma-
tion. Here we emphasize key events that will be discussed in the context of single-
cell transcriptomics in later sections. Akin to other organs in the vertebrate mouth
cavity, the tooth develops from the first pharyngeal arch that encompass both the
mandibular and maxillary processes. In humans, pharyngeal arches are formed
around the fourth week of development, while in mice they first become apparent
around embryonic day (E) 8.5. Much like an apple with a thin layer of skin, the
pharyngeal arch comprises a bulk of mesenchymal cells that are ensheathed by a
continuous epithelial layer of ectodermal and endodermal origins [7]. The ectoderm
overlays the outer arch, while the endoderm coats the inner surface. The mesenchy-
mal cells also have dual origins. Whereas the core contains cranial mesoderm that
gives rise to most of the head muscles, the rest of the mesenchyme is derived from
cranial neural crest cells with broad fate potential. Unlike mesodermal cells, the
cranial neural crest is derived from the ectoderm through a process known as epithe-
lial-to-mesenchymal transition (EMT). In this process, some ectodermal cells, also
known as ectomesenchyme, delaminate from the ectodermal epithelium in response
to Wnt and Fgf signals and migrate to populate the forming pharyngeal arches [8–
10]. In the cranial region, EMT occurs prior to the neural fold closure and the ecto-
mesenchyme arises from a group of E-cadherin-expressing non-neural ectodermal
cells lateral to the N-cadherin-expressing neural ectoderm [11, 12] (Fig. 19.1a).
Subsequently, ectomesenchyme gives rise to a wide range of cell types in the man-
dible and maxilla, including bone-forming osteoblasts, cartilage-forming chondro-
blasts, odontoblasts that produce dentin, pulp cells, and tendon and ligament
precursors [13, 14]. Therefore, the mechanism that controls diverse cell fates in the
cranial neural crest has long been an important area of research. We will highlight
several recent studies that used single-cell transcriptomics to explore the complexity
of this population.
As the first pharyngeal arch develops, the oral ectoderm is initially patterned into
several subdomains. In mice, the proximal and distal portions of the oral ectoderm
express Fgf8 and Bmp4, respectively, at E9.5, which help specify the molar and
incisor fields along the proximal-distal axis of the arch [15–17]. Ectodermal cells at
336 J. K. Hu and A. Sharir

a b

Neural Plate
Neural Fold Spatial and Dental lamina Placode Bud
Non-Neural temporal
Ectoderm regulation of Invagination
Signaling
lineage interactions
Mes.
specification? condensation

Genetic & Cap Bell

genomic
Epithelium
changes?
Enamel knot
Follicle Am Mesenchyme
Od Condensing mesenchyme
Papilla
Alveolar bone
Neuroglial CNCCs Pulp

Ectomesenchyme
Osteoblasts, chondroblasts, Heterogeneity?
odontoblasts etc Lineages?
Pulp stem cell regulation?

Fig. 19.1 Ectomesenchymal development and tooth formation. (a) Ectomesenchyme is formed
from the non-neural ectoderm adjacent to the neural fold prior to its closure. Ectomesenchymal
cells delaminate from the ectoderm as a result of epithelial-to-mesenchymal transition (EMT) and
migrate into the developing pharyngeal arches. They give rise to several cell types, including
osteoblasts, chondroblasts, and odontoblasts. However, the spatiotemporal dynamics of specifica-
tion has been a long-standing question, as are the associated genetic changes. (b) Signaling interac-
tions between the forming dental epithelium and the underlying ectomesenchyme drive tooth
development and morphogenesis. Mesenchymal condensation takes place during early differentia-
tion of the dental mesenchyme, which proceeds to form the dental follicle and papilla. Papilla then
develops into the heterogeneous tissue of the dental pulp. Little is known about the different pulp
cell populations, how they are formed, and how they are regulated. Am ameloblasts, Od odontoblasts

the tooth field then become thickened and begin to stratify, forming the dental plac-
ode that bends toward the underlying ectomesenchyme [18]. Subsequent tooth
development depends on a series of reciprocal signaling interactions between epi-
thelium and mesenchyme. Signals from the epithelium specify the ectomesenchyme
toward the dental mesenchymal fate, while the mesenchyme induces further devel-
opment of the dental placode. As epithelial-mesenchymal interactions also underlie
the development of other ectodermal appendages, such as salivary glands, taste
buds, and hair, comparing the signaling responses between these organs will shed
light on mechanisms that drive the development of ectodermal organs and how they
generate diverse cell types and distinct morphologies.
In response to the signaling interactions, the tooth placode further invaginates
into the dental mesenchyme and undergoes a series of morphological changes
from a bud, through a cap, and then to a bell-shaped structure (Fig. 19.1b).
Concurrently, the dental mesenchyme condenses around the developing tooth epi-
thelium. Mesenchymal cells within the epithelial cap, now called the dental
papilla, give rise to dentin-forming odontoblasts and dental pulp, while the
19 Elucidating Tooth Development and Pulp Biology by Single-Cell Sequencing… 337

mesenchyme encapsulating the dental cap and papilla, also called the dental follicle,
differentiates into various tissues, including the periodontal ligament, the cemen-
tum, and the alveolar bone [19]. The dental mesenchyme is thus capable of forming
multiple cell types. Nevertheless, key questions relating to the extent of cellular
heterogeneity in the dental pulp, when different cell lineages arise, and how the
specification of each cell type is regulated (Fig. 19.1) remained largely unresolved,
until recently developed single-cell technologies provided the means to address them.
In erupted teeth, the tooth pulp continues to maintain a group of dental pulp stem
cells, which help repair injured dentin by forming new odontoblasts in a process
known as reparative dentinogenesis [20]. Remarkably, these stem cells are also
capable of differentiating toward a wide range of other lineages under different
in vitro or in vivo conditions, acquiring odontogenic, osteogenic, chondrogenic,
myogenic, adipogenic, or even neurogenic fates [21]. In this context, single-cell
technology again offered scientists a powerful tool to dissect the dental pulp popula-
tions in mature teeth and to explore potential mechanisms that regulate this regen-
eration process. We discuss these studies in more details later, following a brief
overview of the scRNA-seq technique.

19.1.3 Basic Principles of scRNA-Seq

The goal of this section is to provide a synopsis of the scRNA-seq methodology. For
a detailed explanation of the underlying technology, experimental and computa-
tional procedures, the reader may refer to other resources [22–25]. Notably, scRNA-
seq encompasses a range of platforms that use different methods to isolate single
cells and different chemical methods to generate the sequencing libraries [26]. The
commercially available, microfluidics-based 10× chromium system is widely used
by biologists, including many papers we discuss herein. In addition, single-cell
technology is not limited to measuring gene expression levels, as it also includes
applications for measuring DNA methylation, chromatin accessibility, protein
expression, etc [27]. However, we focus on the more mature technology of RNA-
seq, which has been employed in most of the recent pulp studies.
scRNA-seq technology enables profiling the transcriptomes of thousands of indi-
vidual cells from one or multiple samples. A transcriptome is the whole set of mes-
senger ribonucleic acid (mRNA) molecules that are expressed by a biological
sample, whether it is a cell, a tissue, an organ, or an organism. These mRNAs carry
information that the cellular machinery uses to build proteins and, thus, each mRNA
represents the transcriptional output, or transcript, of a gene. The main advantages
of scRNA-seq technology are its ability to quantify transcripts at single-cell resolu-
tion, its unbiased nature, and its power to detect rare cell populations that would be
missed in bulk sequencing, where the average gene expression from the entire tissue
is measured [28]. scRNA-seq does not depend on purification of discrete cell popu-
lations, which is often biased by the use of predefined markers. Thus, for studying
developing organs, it offers high sensitivity to the heterogeneity of cells and to inter-
mediate transition states during differentiation.
338 J. K. Hu and A. Sharir

a b c d

e f g h

Expression profile
Cell 1
Cell 2
Cell 3
...
Cell n

Fig. 19.2 General workflow of scRNA-seq. (a). Tissue dissection and cell isolation. (b) Single-­
cell dissociation by enzymatic or mechanical methods. (c) Lysing of viable single cells releases
their mRNA. (d–g) Barcoding and library preparation are followed by sequencing and gene
expression profiling. (h) Bioinformatic tools are used for dimensional reduction and visualization
of the data. (Created with BioRender.com)

Acquiring a sufficiently high number of healthy cells is a critical first step in

conducting a successful scRNA-seq experiment. Therefore, it is essential to empiri-
cally determine the appropriate cell dissociation methods and conditions for the
tissue of interest prior to the actual experiment [29, 30]. The subsequent steps of
scRNA-Seq (Fig. 19.2) are isolation of dissociated single cells (e.g., using microflu-
idics or fluorescence-activated cell sorting (FACS)), lysing viable single cells to
release their mRNA, generation of cDNA such that cells are individually tagged and
barcoded, and construction of high-throughput, next-generation sequencing
19 Elucidating Tooth Development and Pulp Biology by Single-Cell Sequencing… 339

libraries. The result is a set of sequencing reads that are specific to individual cells,
which are then matched to the reference genome or transcriptome to retrieve their
identities. Numbers of reads for each gene are converted into expression estimates,
which are corrected through normalization and scaling across all cells. Such nor-
malized expression estimates are then used as the input for dimensional reduction
and visualization platforms, which group similar cells together, annotate them, and
identify differentially expressed genes between groups. A large array of downstream
bioinformatic tools have also been developed to enable the prediction of many addi-
tional variables, such as cell trajectories, cell-cell interactions, transcription factor
enrichment, and function enrichment.
While the basic steps of scRNA-seq are translatable between studies, certain
limitations and challenges should be considered when designing scRNA-seq experi-
ments to study tooth development and pulp biology, as well as when interpreting
their results. For example, delicate and fast dissection is required to isolate the target
cells, which are encapsuled within a mineralized shell. Relative to other organs, the
yield of viable cells from each tooth is low and enzymatic digestion conditions
should be optimized to ensure cell viability and separation [31]. The relatively small
number of sequenced cells also demands rigorous downstream analyses to ensure
correct clustering of cells. One solution to the low cell numbers is to pool cells from
several donors; however, this could complicate the validation of the results. As
human specimens are scarce, very few samples, sometimes only one tooth per
experimental condition, were sequenced in some of the studies presented here.
Consequently, additional studies are required to account for biological variability
and provide reproducibility.

19.1.3.1 A Methodological Comparison of the Reviewed Studies

While all the studies discussed in this chapter applied well-established scRNA-seq
protocols, they differed in several important aspects, as illustrated in Table 19.1.
These differences should be considered when interpreting results and comparing
findings between studies.
Table 19.1 Summary of the main findings of the studies discussed in this chapter as well as their similarities and differences in study designs, sample preparation,
340

scRNA-seq strategies, and bioinformatic tools

Study design Sequencing details
Age/
developmental Tooth/anatomic Sample Health Cell Sequencing Analyzing
Paper Species stage region numbers status isolation # Cells # Reads/cell platform platform Main findings
Formation and Soldatov Mouse E8.5–E10.5 Cranial neural >3 embryos/ NA FACS At E8.5, 20,000– Smart-­seq2 PAGODA Sequential bifurcating fate
patterning of the et al. (2019) crest cells sample 1345; E9.5, 35,000 decisions in NCCs and
ectomesenchyme (Wnt1-­CreER) 1088; other CNCCs are biased toward
isolated from regions and the mesenchymal fate during
embryo heads timepoints, delamination
300–1400
Tatarakis Zebrafish 12; 14; 18; 20; Cranial NC cells 6–8 NA FACS Not reported Not reported 10X Seurat CNCC fate decisions are
et al. (2021) 24 and 30 h that contribute to embryos/ Genomics determined during
post-fertilization the first sample, 1 mid-­migration, first through
(from the onset pharyngeal arch sample/ a transitional state and then
to completion of (PA1) isolated timepoint through bifurcation
neural crest using tg
migration) sox10:nEOS after
photo-­conversion
Fabian et al. Zebrafish Embryonic (1.5 Cranial neural Multiple NA FACS scRNA-seq, scRNA-seq, 10X Seurat and Migrating CNCCs undergo
(2022) and 2 days crest-­derived cell embryos/ 58,075; 1,000,000; Genomics Signac progressive and
post-fertilization isolated using tg sample; 2 or snATAC-seq, snATAC-­seq, region-­specific chromatin
(dpf)), larval (3 sox10cre 3 samples/ 88,177 75,000/ organization changes to
and 5 dpf), timepoint nucleus acquire specific fates
juvenile (14 and
60 dpf), and
adult (150–210
dpf) stages
Williams Chicken 6–7 ss Citrine+ NC and Multiple NA FACS scRNA-seq, scRNA-seq, 10X Seurat In chicks, fate biases occur
et al. (2019) (somite-stage) surrounding embryos per 2359; 152,318; Genomics before migration and
citrine− non-NC sample snATAC-seq, snATAC-­seq, (both correspond to changes in
cells isolated 1259 5923/nucleus scRNA-seq chromatin accessibility
after and
electroporation of snATAC-seq)
the cranial
NC-specific
enhancer NC1
J. K. Hu and A. Sharir
 Xu et al. Mouse E10.5 Dissection of 5 mandibles/ NA Dissection 10,586 28,339 10X Seurat Complementary Shh and
19

(2019) mandibles sample; 1 Genomics Bmp4 signaling pathways

sample pattern the mandibular arch
sequenced along the oral-aboral axis
Yuan et al. Mouse E10.5, E12.5, Dissection of 2 embryos/ NA Dissection E10.5, 3058; 80,000 10X Seurat In the mandibular arch,
(2020) E14.5 mandibles sample; 1 E12.5, 4705; Genomics mesenchymal cell lineages
sample/ E14.5, 6788 arise through a stepwise
timepoint bifurcation process
Tooth Wang et al. Mouse E10.5, E11.5, E10 and E11, Multiple NA Dissection 4676–11,025 52,196 10X R, Python, Identified Cd24a++/Plac8+
development (2022) E12.5, E13.5, incisor and embryos/ (depending Genomics Seurat, coronal papilla cells as a
E14.5, E16.5 molars together; sample; 1 on stage and SCANPY group of odontogenetic
E12, E14, molars sample/ tooth) mesenchymal cells
and incisor timepoint
separately; E16,
also M1 and M2
Jing et al. Mouse E13.5, E14.5, Dissection of 2 embryos/ NA Dissection E13.5, Mean 80,000 10X Seurat Apical papilla cells are
(2022) E16.5, P3.5, teeth and sample; 1 21,416; Genomics bipotent progenitors that
P7.5 surrounding sample/ E14.5, give rise to the pulp cells
tissues timepoint 26,461; and odontoblasts
E16.5,
29,766;
P3.5, 19,134;
P7.5, 15,462
Ye et al. Mouse E9.5, E12.5 Epithelial tissue 6 embryos/ NA E9.5, E9.5, E9.5:43,421; 10X Seurat The dental epithelium is
(2022) from the sample; 1 Dissection; 13,081; E12.5:19,585 Genomics specified through a
mandible sample/ E12.5, E12.5, progressive regionalization
timepoint FACS 11,131 process

(continued)
Elucidating Tooth Development and Pulp Biology by Single-Cell Sequencing…
341
Table 19.1 (continued)
342

Study design Sequencing details

Age/
developmental Tooth/anatomic Sample Health Cell Sequencing Analyzing
Paper Species stage region numbers status isolation # Cells # Reads/cell platform platform Main findings
Post-eruption and Pagella et al. Human 18–35 years 3rd molar 5 teeth/1 Healthy Dissection Dental pulp, 50,000 10X Seurat Dental pulp MSCs contain
adult stages (2021) sample 32,378 Genomics three subpopulations; pulp
and periodontium progenitor
cells are quite similar
Shi et al. Human Two different 3rd molar 2 teeth/1 Healthy Dissection 9855 28,000 NovelBio Seurat Provided a cell interactome
(2021) developmental sample Bio-Pharm landscape for the postnatal
stages (A and Technology pulp and discovered
D) Co., Ltd signaling pathways
regulating the development
of various dental cells
Opasawatcha Human 21–36 years 3rd molar (1-#18, 4 teeth/1 1 healthy, 3 Dissection 6810 50,000 Hiseq system Seurat Inflammation, resolution,
et al. (2022) 3-#28) sample caries (Illumina, and regeneration may occur
(deep and USA) simultaneously in deep
superficial) caries; hematopoietic stem
cells could be a source of
pro-inflammatory cytokines
Krivanek Human 18–31 years 7 third molars, 6 7 adult teeth; Healthy Dissection 41,673 NA Smart-­seq2 PAGODA Growing and even fully
et al. (2021) apical papillae of 6 growing and caries or 10X developed human pulp
3 donors teeth Genomics contain cell populations with
regenerative transcriptomes
Mouse 2–4 months Lower jaw 78 incisors; Healthy Dissection 9164 NA 10X PAGODA Found a Foxd1+ multipotent
incisors, first 48 first Genomics population of mouse MSCs
molars molars and classified the
odontoblast and pulp cell
transcriptional states across
their differentiation
J. K. Hu and A. Sharir
19 Elucidating Tooth Development and Pulp Biology by Single-Cell Sequencing… 343

19.2 Formation and Patterning of the Ectomesenchyme

All tooth-related mesenchymal cells, including odontoblasts, pulp cells, periodontal

cells, and associated bones, are descendants of cranial neural crest-derived ectomes-
enchyme. Understanding the process by which neural crest cells give rise to such
diverse populations has therefore been an important quest in developmental biology.
One of the key questions is whether premigratory cranial neural crest cells are mul-
tipotent, i.e., have the ability to become different cell types, or prepatterned early on
to adopt a particular fate (Fig. 19.3). Cell labelling and lineage tracing studies in
various model organisms have produced contradictory results, in part because of
limitations to precisely label all neural crest cells [32–34]. Several recent studies
revisited this decades-old question using single-cell data to computationally deter-
mine the timeline of cell differentiation and lineage divergence, which were then
verified by in situ hybridization and labelling experiments.
Soldatov et al. [35] used Wnt1Cre to label both trunk and cranial neural crest
populations in E8.5–E10.5 mouse embryos and then sorted labelled cells for down-
stream high-coverage sequencing using Smart-seq2. Their results showed that pre-
migratory crest cells are not biased toward any specific fate. However, upon
delamination, neural crest at the cranial level begins to exhibit a mesenchymal bias,
while the trunk neural crest adopts a neuronal fate (Fig. 19.3). As scRNA-seq analy-
sis allows comparing transcript levels between grouped cell populations, differen-
tially expressed genes can be identified. In addition to marking the population, this
conveys information about the regulation and function of the cells. In this manner,

scRNA-seq studies reveal lineage bifurcations

Classical Model
Mouse Zebrafish Chick
Pre-migratory
NCCs NCCs CNCCs CNCCs
at PA1

Migrating
NCCs
Trunk

Postotic/ Cranial
Trunk

Lineage
Commitment Glia Neurons Pigment Sensory
Mesenchyme neurons
Pigment
Skeletal- cells Mesenchyme
Mesenchyme cells Autonomic (chondrocytes, & glia Neurons related Neurons
neurons osteoblasts, & Glia cells & Glia
& glia odontoblasts)

Fig. 19.3 Cranial neural crest cell differentiation in different species. Addressing an enduring
question in developmental biology, scRNA-seq analyses revealed that cranial neural crest cells
(CNCCs) are specified through different processes in different species. Whereas in mice and
zebrafish, specification takes place in migrating CNCCs, in chicks it is already underway in premi-
gratory CNCCs. In addition, while the traditional model posited a single progenitor type giving
rise to all differentiated cell types, scRNA-seq studies showed that CNCC differentiation is in fact
a series of bifurcation events
344 J. K. Hu and A. Sharir

the transcription factor TWIST1 was found to be specifically expressed in the

delaminating cranial neural crest. Functional studies showed that it drives the speci-
fication of a mesenchymal fate [35]. Fate determination thus takes place during
migration of neural crest cells and follows a series of binary bifurcation points,
where the initially coactivated transcriptional programs of competing cell fates give
way to one fate-specific and committed program (Fig. 19.3). Such a stepwise binary
process is also observed in the migrating cranial neural crest cells of zebrafish. By
combining scRNA-seq data from multiple developmental stages in zebrafish with
pseudotime analysis, which infers temporal lineage progression, transitional cells
with dual fate markers were detected at bifurcation points [36]. Specifically, migrat-
ing neural crest cells first adopted a transitional state, expressing both pigment and
skeletal cell markers, and then split into two distinct cell types. In the next bifurca-
tion point, skeletal precursors gave rise to neural/glial cell populations (Fig. 19.3).
The order and pattern of neural crest differentiation in zebrafish are thus distinct
from those observed in mice.
A second zebrafish study integrated scRNA-seq with single-nucleus assay for
transposase accessible chromatin sequencing (snATAC-seq), which interrogates
chromatin accessibility. This study revealed that progressive chromatin remodel-
ing underlies transcriptional changes and differentiation of migrating cranial
neural crest cells [37]. In chick embryos, changes in chromatin accessibility also
explain early fate decisions between neural and canonical/mesenchymal pro-
grams [38]. Surprisingly, unlike in mice and zebrafish, cell fate segregation
occurred in chick premigratory cells (Fig. 19.3). The discrepancies between
these studies may reflect differences among species, as well as between cells
from different stages and locations. It should also be noted that while zebrafish
do not form oral teeth, they develop pharyngeal teeth from mesenchymal cells of
the seventh arch. These cells begin to express tooth transcriptional signatures by
3 days post-fertilization, following placode formation from the endodermal epi-
thelium [37, 39]. On the contrary, mammalian dental mesenchyme is derived
from the first pharyngeal arch and induced by signals from the oral ectoderm. As
only early migrating cranial neural crest cells were examined in the mouse study
described here, tooth-specific transcriptional signatures were absent.
As ectomesenchymal cells populate the developing first pharyngeal arch, they
are patterned along different axes. For instance, as mentioned above, Fgf8 and
Bmp4 pattern the proximal-distal axis of the mandibular arch ectomesenchyme by
respectively activating the expression of transcription factors Barx1 in the proxi-
mal arch and Msx1/2 in the distal arch [40]. However, the mechanism that deter-
mines oral-aboral patterning remained elusive until recently, when a scRNA-seq
analysis of E10.5 mouse mandibular arch revealed complementary hedgehog and
BMP signaling events in the oral and aboral parts of the mandible [41]. Sequencing
results informed subsequent functional studies, which employed both genetic abla-
tion and ectopic activation of hedgehog signaling in postmigratory neural crest
cells. These experiments demonstrated that hedgehog acts by inducing the expres-
sion of transcription factors Foxf1 and Foxf2 in the oral ectomesenchyme, which in
turn delineate BMP signaling in the aboral region, thus patterning the mandibular
19 Elucidating Tooth Development and Pulp Biology by Single-Cell Sequencing… 345

arch along the oral-aboral axis. By integrating scRNA-seq results from E10.5–
E14.5 mandibular arches, a second study showed that mesenchymal cells from the
proximal arch either migrate to, or give rise to, cells in the more distal arch [42].
Concurrently, these cells undergo fate determination through a stepwise bifurca-
tion process, splitting first into a stromal cell lineage and a common progenitor
population, and then to separate odontogenic/osteogenic and chondrogenic/fibro-
blast lineages. This sequential lineage restriction manner produces the earliest
odontogenic populations.

19.3 Odontogenesis from Bud to Bell Stages

Odontogenesis, which encompasses tooth development through bud, cap, and bell
stages, is a well-coordinated process. Decades of research have revealed the complex
signaling and genetic interactions between the developing dental epithelium and
mesenchyme. However, many outstanding questions remain; for instance, how dif-
ferent cell lineages arise and how their specifications and functions are regulated
transcriptionally (Fig. 19.1b). Because tooth morphogenesis in mice is comparable
to that in humans, the mouse tooth has served as the primary model system for study-
ing odontogenesis [43]. It should be noted, however, that mice are monophyodont,
forming only one set of teeth, and only have incisors and molars, separated by a
toothless space called the diastema. In contrast, humans are diphyodont, display
sequential development of deciduous and permanent teeth, and form both canines
and premolars. Nonetheless, the expression and functions of key developmental
genes in teeth are largely conserved across different experimental models [44, 45].
Knowledge gained from recent single-cell transcriptomic explorations of developing
mouse teeth [46–48] should therefore be applicable to humans, especially regarding
the specification of dental field and cell fate decisions of dental mesenchyme.
Odontogenesis begins in the oral ectoderm with the establishment of the dental
placode at around E11 in mice, which is transcriptionally distinct from the rest of
the oral epithelium and expresses dental markers such as Pitx2, Irx1, and Shh. It is
therefore of interest to understand how the dental epithelium is specified and pat-
terned as a stripe in the dental field. By combining scRNA-seq and spatial mapping
of identified genes in the mandibular arch epithelium at E9.5 to E12.5, it was dem-
onstrated that the mandibular ectoderm is initially more homogeneous and broadly
expresses tooth-specific transcription factors. These dental-like precursor cells then
give rise to both the anterior and posterior non-dental epithelia, which progressively
expand and delineate the boundaries of the dental field [48]. The dental field there-
fore arises as the ectoderm becomes increasingly regionalized at the transcriptional
level and the tooth placode is defined by PITX2- and IRX1-­targeted gene regulatory
networks. Notably, suprabasal cells in the forming tooth bud express many regula-
tors of actin organization and cell motility, enabling epithelial cell rearrangement,
which was shown to mechanically power tooth invagination [49].
Although the epithelial signals Bmp4 and Fgf8 have been proposed to specify
the incisor and molar tooth types [16, 40], results from genetic perturbation studies
346 J. K. Hu and A. Sharir

did not yield a definitive evidence of tooth transformation, for example, of molars
into incisors [50–52]. The question of how tooth types are specified hence remain
open. A recent unbiased investigation of incisor and molar development, where
scRNA-seq data from E10.5–E16.5 dental epithelium and mesenchyme were inte-
grated, revealed that although they were identifiable by the respective expression of
Bmp4 and Fgf8 in epithelium and Msx1 and Barx1 in mesenchyme, incisor and
molar cells initially had similar transcriptional profiles [46]. However, from E12.5
onward, the incisor and molar mesenchymal cells begin to express unique markers,
in part due to changes in chromatin accessibility. Furthermore, computational infer-
ence of gene regulatory networks identified Hand1, Alx1/3, and Pax3 as potential
key transcription factors in the incisor and Tbx15, Lhx6, and Tfap2b as the molar
counterparts. Concurrently, transcriptional differences also separate the diastema
from the neighboring odontogenic regions [48, 53]. Future works will examine the
functional requirement as well as sufficiency of these genes in determining tooth
types and diastema fate, providing insight into the genetic regulation of cell popula-
tions in the dental field.
Another scRNA-seq study found that as tooth development proceeds, genes
important for each stage are upregulated in specific cell populations. Many of these
genes are components of signaling pathways, including Fgf, Wnt, Tgfβ, hedgehog,
Notch, and ectodysplasin (Eda), reflecting the complex signaling interactions
between cells during tooth development [45]. While these signals are essential for
tooth morphogenesis and for further development of the dental mesenchyme, how
dental mesenchyme gradually gives rise to diverse cell types in the tooth pulp and
periodontal tissues is largely unknown. To begin tackling this question, Jing et al.
performed scRNA-seq using cells from the mouse molar and surrounding tissues at
various developmental time points between E13.5 and postnatal day (P) 7.5 [47]. At
E13.5, the Tfap2b+/Lhx6+ postmigratory ectomesenchyme, which has just commit-
ted to the dental fate, appears as a homogeneous population with the potential of
giving rise to all dental mesenchymal lineages (Fig. 19.4). At E14.5, the mesenchy-
mal lineage bifurcated into two distinct populations; Crym+/Egr3+/Fgf3+ dental
papilla in the future pulp region and Epha3+/Fxyd7+/Foxf1+ dental follicle that
encapsulates the tooth germ. These fate decisions may be determined by the two
highly active gene regulatory networks detected at this stage, one governed by
Barx1 and the other by Foxf1, which were enriched, respectively, in the emerging
dental papilla and dental follicle [46].
By E16.5, these cells became more diversified, as the dental papilla split into
coronal (toward the future crown) and apical (adjacent to the future root) regions,
and the dental follicle divided into lateral and apical domains [47] (Fig. 19.4). At
P3.5, Phex+/Ifitm5+ odontoblasts were observed underneath the newly secreted
dentin, while the dental papilla consisted of the coronal, middle, and apical popula-
tions. Importantly, RNA velocity and pseudotime analyses predicted that apical
papilla contains bipotent progenitors that give rise to pulp and odontoblast lineages
(Fig. 19.4). Likewise, apical pulp cells were the most proliferative at this stage and
19 Elucidating Tooth Development and Pulp Biology by Single-Cell Sequencing… 347

Bud Cap Bell Late bell

CD24High
High odontogenic
+ potential
Kidney
Dental capsule
mesenchyme Low odontogenic
+ potential
CD24Low
Bipotent
progenitors Lateral follicle
Apical follicle
Apical papilla
Coronal papilla
Middle papilla
Odontoblast

Fig. 19.4 scRNA-seq reveals differentiation of the dental mesenchyme along different cell lin-
eages. Dental mesenchymal cells first give rise to follicle and papilla progenitor cells, which then
differentiate into various populations that occupy distinct anatomical positions. At the late bell
stage, cells in the apical papilla function as bipotent progenitors that can differentiate into either
papilla cells or odontoblasts. Cells in the coronal papilla are characterized by high CD24 expres-
sion and retain high odontogenic potential when recombined with dental epithelium and cultured
in kidney capsules. Cells with low CD24 expression are comparatively less odontogenic. Together,
these findings demonstrate the heterogeneous nature of the dental pulp

their capability to generate both cell types was confirmed by genetic lineage tracing
using Fgf3-CreERT2 to specifically label this population. Differentiation of the den-
tal mesenchyme is therefore a series of bifurcations or trifurcations that generate
increasingly diverse and regionalized cell types. Interestingly, several FOX (fork-
head box) transcription factors were highly enriched in odontoblasts and different
papilla populations at P3.5, such as Foxj3 in odontoblasts, Foxn3 in the coronal
papilla, and Foxp4 in the apical papilla. While Foxp4 is required for proper differen-
tiation of the periodontal ligament [47], it will be interesting to dissect the individ-
ual and combinatorial functions of FOX family members in the developing tooth
mesenchyme.
The notion that the coronal papilla is a separate mesenchymal population was
also demonstrated by Wang et al. (2022), who identified a group of Cd24a++/
Plac8+ cells. Using tissue recombination methods, where sorted or dissected
Cd24a++/Plac8+ cells were recombined, or packaged, with non-odontogenic epi-
thelium and then grown under kidney capsules, they showed that these cells are
odontogenic and capable of inducing formation of new teeth. Conversely, Cd24a+
cells from the apical/middle papilla and Cd24a- mesenchymal cells were signifi-
cantly less odontogenic. These findings imply that whereas cells in the apical pulp
function as bipotent progenitors that can form different mesenchymal lineages,
coronal papilla cells are odontogenic and can induce the developmental programs of
tooth formation (Fig. 19.4). These functional differences should be considered
when using pulp cells for regenerative purposes, either to produce an array of mes-
enchymal cell types or to induce de novo tooth development.
348 J. K. Hu and A. Sharir

19.4 Post-Eruption and Adult Stages

Tooth growth during the post-eruption phase involves highly coordinated processes,
such as alveolar bone resorption, root anchoring, and tissue mineralization. These
processes profoundly influence the internal architecture and composition, size and
shape of the tooth, and, thereby, its function. Understanding the detailed cellular
hierarchies, interactions, and cell type-specific signaling activities during tooth
growth is therefore necessary for advancing regenerative approaches. Here too,
scRNA-seq offers a unique opportunity to elucidate this process in an unbiased
manner and at high cellular resolution.
Based on their transcriptomic signatures, scRNA-seq analyses of growing third
molars harvested from human patients revealed all the known cell types of the pulp,
including odontoblasts, MSCs, and endothelial and immune cells. These studies
also revealed a multitude of novel genes that help classify each cell type within the
growing pulp. In many cases, these new markers separated cell types into subpopu-
lations, which could help elucidate cell type-specific functions in the growing pulp.
For example, based on differentially expressed markers, both Krivanek et al. [54]
and Pagella et al. [55] identified three main types of endothelial cells in the molar
pulp. However, the lists of markers slightly differed, likely due to differences in
study designs and bioinformatic tools used (see Table 19.1).
Like most biological processes, tooth growth is orchestrated by interactions
between cells and transcription factors, often through ligand-receptor complexes.
These communication networks could be inferred from the transcriptomic data [56].
For example, by measuring the expression levels of ligands and receptors within
each pulp cell type, Shi et al. [57] showed that ligands released from monocytes
(IL1B and IL1A), osteoblasts (BMP4, TGFB3, BMP5), and T cells (TGFB1) could
function as regulators of renewal genes in apical papilla stem cells. Their computa-
tional analysis further predicted that these ligands mainly act on FGFR1, which
regulates 28 downstream renewal genes, including Msx1, Ptch1, and Sox9. SCENIC,
a computational pipeline that infers gene regulatory networks, predicted Msx1 as
the key transcription factor.
A competent immune system is essential for the dental pulp to oppose microbial
infections inflicted by physical injuries to the tooth, gum, or other oral surfaces [58].
Recent scRNA-seq analyses uncovered the detailed composition and organization
of the immunocompetent cells within the growing pulp. Analysis of gene expression
in different populations enabled inference of their signaling interactions, shedding
light on how the immune system operates during tooth growth and development.
Interestingly, all analyses of the growing third molars showed that even in healthy
teeth, immune cells constitute a larger than expected portion of the pulp cells. This
could reflect a heightened state of immune activation during the eruption stage, such
as the presence of active macrophages and osteoclasts required to absorb the cover-
ing bone. The unexpected high numbers of immune cells may also result from the
increased sensitivity of scRNA-seq, as compared to methods such as marker-based
flow cytometry. T cells, neutrophils, macrophages, and dendritic cells were identi-
fied based on their transcriptomic profiles and, in many cases, further divided into
19 Elucidating Tooth Development and Pulp Biology by Single-Cell Sequencing… 349

subpopulations, revealing a previously underappreciated diversity of pulp immune

cells. Identifying these distinct cell types also provides clues as to specific immune
functions during the pulp growth period. For example, Shi et al. [57] split T cells
into eight subtypes and discovered that younger teeth contain more naïve T cells
(Th17) and less cytotoxic (CD8T) and memory cells, when compared to a more
developed tooth. Krivanek et al. [54] uncovered specific distributions of macro-
phage subtypes in different pulp domains. Macrophages expressing lymphatic ves-
sel endothelial hyaluronan receptor 1 (LYVE1+) resided away from odontoblast
layers, whereas LYVE− macrophages were scattered ubiquitously and occupied the
odontoblast layer as well. It will be interesting to investigate the potential associa-
tion of these macrophage subsets with specific immune cell homing factors, which
could be manipulated to protect teeth against infections.
Transcriptomic comparison between healthy and diseased teeth offers new per-
spectives on the function of the immune system during injury and subsequent recov-
ery. By comparing the transcriptomes of caries-affected and healthy human molars,
Opasawatchai et al. [59] found that immune cell composition in the dental pulp was
altered in response to deep, but not superficial, caries, as B cells and dendritic cells
were present only in pulp with deep caries. Other scRNA-seq studies also uncov-
ered alterations in the activity level of signaling pathways and predicted certain
cell-cell interactions that are likely essential to the pulpal defense mechanisms. For
example, based on differences in expression of ligands and receptors between
healthy and deep caries teeth, Shi et al. [57] showed that IL1B from monocytes and
TGFB1 from T cells regulate dozens of genes that are associated with tooth repair
and renewal.
In addition to differentiated pulp cells, recent scRNA-seq-based studies have
begun to uncover the diversity and hierarchy of stem cells residing within the dental
pulp, known as dental mesenchymal stem cells (DMSCs). Understanding how
DMSCs interact with other pulp cells to make cell-fate decisions during growth and
repair is key to our ability to use them in a clinical setting. For example, Krivanek
et al. [54] found in the apical pulp region of human teeth, where DMSCs reside, two
subpopulations of active progenitor-like cells and upstream stromal-like cells. By
comparing scRNA-seq data from growing third molars to those of adult non-grow-
ing teeth, they found certain apical-distal and growth-related genes in the growing
molar alone. Interestingly, an apical-like residual cell population is present also in
the adult tooth and could be targeted for reparative responses. Lastly, by assessing
gene expression dynamics during the cell cycle in the growing apical papilla region
of the third molar, Shi et al. [57] identified genes that may have a role in the apical
renewal process.

19.5 Summary

The ultimate goal of dental research today is to find a way to replace injured or
missing teeth with newly grown tissues. The dental pulp, which harbors a reservoir
of stem cells, holds great promise for realizing that goal. The integration of
350 J. K. Hu and A. Sharir

single-­cell technologies in dental research has considerably enhanced our ability to

identify the diverse cell types that populate the tissue, infer their trajectories, and
uncover principal genes and pathways that regulate pulp development and function.
This technology continues to mature and improve, benefitting from better methods
for sample preparation, workflow automation, and intuitive computational tools for
robust and informative analyses, as well as from decreasing sequencing costs. Thus,
single cell-based approaches are expected to become a basic and powerful tool in
both basic and clinical research, as well as in diagnostics and personalized medicine.

Acknowledgments We apologize sincerely to those authors whose work we are unable to cite
here owing to space constraints. Many of the scRNA-seq studies discussed here include excellent
analyses of cells beyond the dental pulp, which were unfortunately omitted due to the focus on
pulp development. The preparation of this book chapter was supported by the BSF grant 2021007
to J.K.H and A.S; NIH/NIDCR grants R03DE030205 and R01DE030471 to J.K.H; and the Israel
Science Foundation grant 604/21 to A.S.

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Biological Basis for Repair
and Regeneration in Modern 20
Endodontics and New Treatment
Considerations

Carolina Cucco and Jacques E. Nör

Contents
20.1 Introduction 354
20.2 Mechanisms of Pulpal Physiology and Repair 355
20.2.1 Reaction of Dentin and Pulp to Mild Injury: Healing, Regeneration, and
Repair 355
20.2.2 The Pulp-Dentin Complex and Conventional Root Canal Treatment 356
20.2.3 Regenerative Potential of the Dental Pulp and Periapical Tissues 357
20.3 Biological Basis of Regenerative Endodontic Procedures 358
20.3.1 Stem Cells in Repair and Regeneration 360
20.4 Stem Cell Homing for Dental Pulp Tissue Engineering 362
20.5 Stem Cell Transplantation for Dental Pulp Tissue Engineering 363
20.6 Conclusions 364
References 365

C. Cucco (*)
Division of Clinical Essentials and Simulation, School of Dentistry, University of Detroit
Mercy, Detroit, MI, USA
e-mail: [email protected]; [email protected]
J. E. Nör
Department of Cariology, Restorative Sciences, Endodontics, University of Michigan School
of Dentistry, Ann Arbor, MI, USA
Department of Biomedical Engineering, University of Michigan College of Engineering,
Ann Arbor, MI, USA
Department of Otolaryngology, University of Michigan School of Medicine,
Ann Arbor, MI, USA
e-mail: [email protected]; [email protected]

© The Author(s), under exclusive license to Springer Nature Switzerland AG 2023 353
A. B. Fuks et al. (eds.), Contemporary Endodontics for Children and
Adolescents, https://doi.org/10.1007/978-3-031-23980-9_20
354 C. Cucco and J. E. Nör

20.1 Introduction

Achieving long-lasting and complete pulp regeneration in teeth with deep caries or
severe trauma remains a significant clinical challenge. In teeth with immature api-
ces and exposed vital pulp tissue, partial or complete pulpotomy is typically indi-
cated to preserve pulp function and allow for continued root development. In cases
where injury caused pulp necrosis and arrested root development, teeth may remain
with poor crown-to-root ratio, a root with very thin dentin walls, and an open apex.
The ideal treatment in such cases is to regenerate a functional dentin-pulp complex
that would enable completion of root development and thickening of dentinal walls.
Emerging evidence suggests that this can be achieved with the recruitment of apical
stem cells toward the root canal and/or the transplantation of stem cells using a tis-
sue engineering-based approach. In this chapter, we will discuss the evidence that
provides the rationale for stem cell-based regenerative approaches for treatment of
pulp injury or pulp necrosis.
Conservative pulp therapies have been used for many years in an attempt to
maintain pulp vitality in teeth with injury. However, with the discovery of the func-
tion of stem cells in dental pulp tissue [1, 2], the search for biological approaches
that exploit these cells for pulp regeneration has intensified exponentially. It is well
known that the dental pulp is vulnerable to insults, such as caries, infection, and
trauma. While current approaches for treatment of these conditions focus primarily
on the maintenance of the compromised tooth structure, future approaches have as
ultimate goal the complete regeneration of dental tissues (i.e., dentin and pulp),
even in cases of pulp necrosis in young teeth [3, 4]. With the emphasis on tissue
regeneration and maintenance of tooth viability, these new concepts of regenerative
endodontic procedures aim at enhancing the strength of the tooth and sustain (or
recover) pulp vitality [3–5].
With the isolation of postnatal stem cells from various sources in the oral cavity
and the development of biocompatible materials for cell and/or growth factor deliv-
ery, possibilities for alternative, cell-based treatments are becoming more feasible.
Interdisciplinary approaches will be needed to move from replacement to regenera-
tion, involving clinicians as well as cell biologists and material scientists. In this
chapter, we will first discuss mechanisms physiology and repair of the pulp-dentin
complex, which can be applied to recreate signaling events to inspire dental tissue
engineering. Then, we will briefly discuss the biological basis for regenerative end-
odontics, as well as the potential of the pulp and periapical tissues to regenerate. We
will focus on the role of stem cells in repair and regeneration. Finally, we discuss
two of the most current pulp regeneration approaches that use stem cells and tissue
engineering principles. In projecting future directions, we conclude with a brief
discussion of key components necessary to develop effective strategies for dental
pulp regeneration, which might enable us to implement novel regenerative strate-
gies in clinical practice in the near future.
20 Biological Basis for Repair and Regeneration in Modern Endodontics and New… 355

20.2 Mechanisms of Pulpal Physiology and Repair

20.2.1 Reaction of Dentin and Pulp to Mild Injury: Healing,

Regeneration, and Repair

The ability of odontoblasts to respond to injury (e.g., caries, cavity preparation) and
upregulate their secretory activity resulting in deposition of reactionary dentin is
well-established [3]. A critical feature of this response is that the odontoblasts have
to survive the injury. This is in contrast to reparative dentinogenesis, where the
intensity of the injury is of a magnitude that results in odontoblast death and cell
replacement by a new generation of odontoblast-like cells [3, 4]. The process of
reactionary dentinogenesis involves upregulation of odontoblast activity, often in
quiescent cells at the stage of physiological secondary dentinogenesis in response to
the injury stimulus. The nature of the signaling process from this stimulus may be
rather variable and has been hypothesized to result from the release of growth fac-
tors and other bioactive molecules from the dentin matrix during injury [5].
Consequently, the induction of signaling events in these cells are not identical to
those observed in primary dentinogenesis and lead to differences in composition
and structure of the resulting mineralized tissue. By definition, reactionary dentin is
secreted by surviving odontoblasts, and thus other pulp cells are not involved in its
synthesis. A variety of bioactive molecules may participate in the signaling of reac-
tionary dentinogenesis, although relatively few have been characterized. Members
of the TGF-family, including TGF-1, TGF-3, and BMP-7, are capable of upregula-
tion of matrix secretion [6–8] although there may be other molecules that are capa-
ble of participation in these signaling processes.
The relationship between the degree of injury that an odontoblast can withstand
and still survive is unclear. Correlation of caries lesion progression and reactionary/
reparative dentinogenic events is hampered by lack of chronological information on
tissue changes that would distinguish odontoblast survival and renewal [9].
Morphological changes in odontoblasts beneath caries lesions have been reported
[10]. In very active lesions, tertiary dentinogenic processes may be absent alto-
gether [11]. However, these data do not allow for discrimination of reactionary from
reparative dentinogenesis. Similar problems can exist in the study of pulpal
responses beneath cavity preparations where surgical procedures can cause odonto-
blast cell death [12]. Nevertheless, examination of the relationship among depth of
cavity preparation, odontoblast numbers, and the tertiary dentinogenic response
beneath the cavity indicates that if the cavity is prepared carefully enough, extensive
odontoblast loss is seen only when pulpal exposure is approached [13, 14]. Cooper
and colleagues (2011) demonstrated that the depth of the carious lesion is a critical
factor, where a full host response is observed in lesions where the remaining dentin
layer is less than 0.5 mm. Furthermore, the caries progression rate plays an impor-
tant role, where rapidly spreading lesions are characterized not only by a different
consistency and color but also by a differing microbiota [15]. In slowly progressing
lesions, mineral deposition can detain invading bacteria and restrict tissue damage
[16]. Pathogen removal by therapeutic intervention can result in the resolution of
356 C. Cucco and J. E. Nör

inflammation, the elimination of remaining toxins, the secretion of anti-­inflammatory

signals, and the production of tertiary dentin. However, there is a close link between
inflammation and repair, and many proinflammatory mediators in pulpal inflamma-
tion can have differential effects [17] depending on their concentration. Compounds,
such as TGF-® and TNF-〈, but also bacterial components can promote processes of
repair at low concentrations, whereas they can cause detrimental effects at higher
levels. In addition, stem cell differentiation may be controlled by various proinflam-
matory mediators [18]. Not only the initial inflammatory response but also the
reparative phase is characterized by the migration of various immune cells.
Furthermore, nerve fiber sprouting beneath the site of injury [19, 20] is guided by
pulp fibroblasts by means of complement activation and secretion of brain-derived
neurotrophic factor (BDNF), which enhances the outgrowth of neurites [21]. Other
neurotrophic factors such as substance P (SP), calcitonin gene-related peptide
(CGRP), and neuropeptide Y (NPY) may also play a role during regenerative pro-
cesses as they promote angiogenesis and stimulate the deposition of tertiary dentin
[22, 23]. Both nerve growth factor (NGF) and BDNF are expressed in pulp cells and
have been implicated in odontoblast differentiation and thus dentinogenesis [24–26].

20.2.2 The Pulp-Dentin Complex and Conventional Root

Canal Treatment

Teeth are complex organs comprising several mineralized matrices, which enclose
a soft tissue termed the dental pulp. A healthy dental pulp fulfills a number of dif-
ferent tasks, namely, formation of dentin, perception of pain, and transmission of
sensory stimuli from the pulp-dentin complex [27], immunoresponse and cellular
clearance of pathogens, as well as formation of dentin as active defense mechanisms
against invading toxins and bacteria [28, 29]. In young patients, a functional pulp
tissue is essential for the completion of root formation [30]. Irritation caused by
caries or trauma induces an inflammatory tissue response termed pulpitis. Initially,
this inflammatory reaction may be fully reversible, and healing is possible. However,
without therapeutic intervention and with increasing intensity of the stimulus, the
inflammation will likely progress to an irreversible state. Traditionally, the thera-
peutic consequence is to sacrifice the pulp tissue and initiate root canal treatment to
prevent further bacterial spreading into the periapical tissues. The procedure
includes the removal of vital or necrotic pulp tissue, preparation, enlargement, and
disinfection of the root canal system and finally filling with a synthetic material.
Root canal treatment offers high success rates, which are influenced negatively by
the presence of bacteria in the root canal system and existence of periapical lesions
prior to treatment [31]. A common complication that entails retreatment or extrac-
tion of the tooth is repopulation of the root canal system with microorganisms due
to remaining bacteria in inaccessible areas or due to permeable root fillings or coro-
nal restorations [32]. Additionally, dentin is suspected to undergo mechanical alter-
ation after root canal treatment, which makes root-filled teeth more prone to fracture
[33]. Another cause for premature extraction of teeth with root fillings is the
20 Biological Basis for Repair and Regeneration in Modern Endodontics and New… 357

development of caries. The presence of a vital pulp could provide biological defense
mechanisms such as maintenance of interstitial pulp pressure [34] and tertiary den-
tin formation to counteract bacterial invasion, as well as maintenance of nociception
to sense damage [27] and enabling timely therapeutic intervention upon progression
of caries lesion in close proximity to the pulp tissue.
Regenerative approaches have gained increasing interest in the field of endodon-
tics in recent years. Vital pulp therapy is widely advocated for teeth diagnosed with
reversible pulpitis. However, traditional diagnostic schemes are still up for discus-
sion, and preservation of the healthy parts of the pulp rather than complete extirpa-
tion is under consideration even for selected teeth diagnosed with irreversible
pulpitis [35, 36]. The maintenance of pulp vitality is particularly critical in young
patients with incomplete root formation. Bacterial infection and subsequent degen-
eration of pulpal tissue in children and adolescents is mainly due to traumatic
impact. Trauma affects mostly central and lateral maxillary incisors, an aestheti-
cally highly relevant area, with a prevalence of 20–30% in young patients [37].
Immature teeth have large root canals, wide apical foramina, and thin, fracture-­
prone dentin walls, which make root canal preparation and filling difficult. Cvek
(1992) reported on the incidence of cervical root fractures in immature root-filled
teeth, which ranges between 28 and 77% depending on the stage of root develop-
ment and is significantly higher than in mature teeth. The loss of permanent anterior
teeth in young patients due to trauma causes major esthetic, functional, and social
consequences until dental implants can be considered after growth is complete in
adults. Even then, as shown in dental implant studies, facial growth might not be
finalized leading to a progressing infraposition of implants over the years and aes-
thetically unfavorable results [38]. Infection, collapse, and growth arrest of the
alveolar bone after premature tooth loss make aesthetically appealing and func-
tional reconstruction a complex and challenging task. These facts emphasize that
revitalization or guided endodontic tissue repair has been established as a treatment
alternative to traditional root canal therapy or apexification [39]. As such, advan-
tages of pulp regeneration over conventional root canal treatment can be considered
as (1) maintenance or restoration of pulp vitality; (2) immune response and intersti-
tial tissue pressure against invading bacteria and toxins; (3) pain perception as a
warning system; (4) moist, less fracture-prone dentin; (5) formation of reactionary
or reparative dentin to separate the pulp from the site of injury; (6) completion of
root formation in young patients to strengthen thin dentin walls and prevent long-­
term complications; and (7) restoration of healthy periradicular tissues.

20.2.3 Regenerative Potential of the Dental Pulp

and Periapical Tissues

The dental pulp is a complex tissue containing odontoblasts, fibroblasts, macro-

phages, endothelial cells, dendritic cells, lymphocytes, Schwann cells, and progeni-
tor/stem cells [40]. Fibroblasts, macrophages, lymphocytes, and Schwann cells
have a limited lifespan and limited capacity for cell division [41]. Odontoblasts are
358 C. Cucco and J. E. Nör

post-mitotic cells incapable of cell division [40, 42]. Differentiation of primary

odontoblasts during embryonic tooth development requires crosstalk between the
epithelial cells of the inner enamel epithelium and neural crest-derived ectomesen-
chymal cells in the dental papilla [40, 42, 43]. During crown dentinogenesis, the
ectomesenchymal cells in the dental papilla, which are aligned adjacent to the inner
enamel epithelium, receive inductive signaling molecules sequestered in the base
membrane from the epithelial cells and differentiate into primary odontoblasts [42,
44–46]. They subsequently produce crown dentin [45]. In teeth with complete
crown formation, the inner enamel epithelium disintegrates. Similar to primary
odontoblast differentiation in crown dentinogenesis, the primary odontoblast dif-
ferentiation in root dentinogenesis also requires crosstalk between the inner epithe-
lial cells of Hertwig’s epithelial root sheath (HERS) and ectomesenchymal cells of
the apical papilla [47]. When primary odontoblasts are destroyed by caries, trauma,
mechanical insult, or chemical cytotoxicity, progenitor/stem cells in the dental pulp
are capable of differentiating into odontoblasts upon stimulation by appropriate
inductive signaling molecules [1, 48]. The periapical tissues consist of cementum,
periodontal ligament, and alveolar bone. Fibroblasts, epithelial cells, cementoblasts,
osteoblasts, macrophages, endothelial cells, Schwann cells, and progenitor/stem
cells are resident cells of the periodontal ligament [40]. Except for progenitor/stem
cells, other resident cells in the periodontal ligament have a limited lifespan and a
limited capability for cell division. Differentiation of primary cementoblasts
requires crosstalk between HERS cells and neural crest-derived ectomesenchymal
cells in the dental follicle. The ectomesenchymal cells receive inductive signaling
molecules from the epithelial cells of HERS and differentiate into cementoblasts
[40, 42, 43]. Therefore, HERS cells play crucial roles in root development and root
dentin and cementum formation [49, 50]. In mature teeth, the HERS cells break
down into nests of epithelial cell rests of Malassez in the periodontal ligament [40,
50]. When primary cementoblasts are destroyed by trauma or periodontal disease,
progenitor/stem cells in the periodontal ligament are capable of differentiating into
cementoblasts, adipocytes, and collagen-forming cells upon stimulation by appro-
priate inductive signaling molecules [51]. Bone marrow-derived mesenchymal stem
cells in the alveolar bone are also capable of differentiating into osteoblasts, chon-
drocytes, and adipocytes upon stimulation by appropriate inductive signaling mol-
ecules [52, 53].

20.3 Biological Basis of Regenerative Endodontic Procedures

During tooth development, ectomesenchymal cells differentiate into dentin-forming

odontoblasts to produce the dentin matrix and to form the pulp-dentin complex. As
root formation progresses, epithelial cells of Hertwig’s root sheath (HERS) instruct
the underlying mesenchymal cells in the dental papilla to form dentin and pulp tis-
sue of the root [54]. Root formation is completed approximately 3 years after the
20 Biological Basis for Repair and Regeneration in Modern Endodontics and New… 359

crown has entered the oral cavity. The formation of root dentin and pulp happens by
differentiation of cells from a specific stem cell niche, the apical papilla. Both the
apical papilla and HERS are present only until root formation is complete, and epi-
thelial rests of HERS remain as cells of Malassez and may contribute to repair and
maintenance of cementum [55]. A study by Lovelace and colleagues (2011) demon-
strated that the provocation of bleeding into the root canal during a regenerative
endodontic procedure leads to an enrichment of stem cells from the apical papilla in
the root canal, as they are flushed in with the bloodstream. Our understanding is that
these cells drive the process of pulpal tissue formation and differentiate to generate
new dentin to increase the length and thickness, close an open apex, and complete
root formation. The presence of HERS and apical papilla appears to be necessary
for true regeneration to take place. Another source of stem cells is the dental pulp
itself. Even in teeth with complete root formation, the dental pulp harbors a small
percentage of stem cells localized around blood vessels in the perivascular niche
[56]. It has been shown that stem cells from inflamed pulp retain their regeneration
potential [57]. Likewise, it can be assumed that stem cells of the apical papilla can
survive and retain their regeneration potential for prolonged periods of time even in
the presence of peri-radicular lesions. Considerations to extend regenerative end-
odontic procedures to permanent teeth are ongoing [58, 59].
It was recently shown that even in teeth with complete root formation, the provo-
cation of bleeding into the canal results in an influx of mesenchymal stem cells
(MSC) [60]. These cells expressed MSC markers, showed a distinct differentiation
potential, and were found compartmentalized in perivascular niches in peri-­radicular
lesions. This interesting finding opens new perspectives and offers a biological basis
for such procedures in permanent teeth. However, from a biological and develop-
ment point of view, it appears more likely to achieve repair rather than regeneration
in these cases. Any manipulation inside the root canal, such as the use of irrigants
and intracanal medicaments, should be considered under the premise to create the
best possible environment for these cells to exert their regenerative potential. In
conventional root canal treatment, the contact area with the surrounding tissues is
comparably small. The implementation of regenerative procedures requires the
practitioners understanding of the biological basis, and how procedural steps of the
therapeutic intervention will influence cell survival, migration, angiogenesis, prolif-
eration, and differentiation. This will require sufficient disinfection of the root canal
system is as important as to prevent harm to the target cells [61], while at the same
time maintaining dentin-derived signaling molecules that are required for pulp tis-
sue regeneration [62]. Thus, pulp regenerative techniques require procedures (e.g.,
irrigation) that cause minimum damage to cells and dentin-derived morphogenic
signals while allowing for efficient disinfection.
360 C. Cucco and J. E. Nör

20.3.1 Stem Cells in Repair and Regeneration

An important cell source during regular tissue turnover, but also during repair, is the
pool of resident stem cells within the dental pulp. Mesenchymal dental pulp stem
cells can be harvested from permanent teeth [1], deciduous teeth [2], and the apical
papilla of immature teeth with incomplete root formation [47]. Stem cells in the
dental pulp located in the perivascular niche [63] remain quiescent until they are
recruited to the site of injury upon chemotactic signaling and differentiate into
odontoblast-like cells [64]. However, pulp stem cells also express toll-like receptors
(TLRs) and are capable of pathogen recognition [65] and may also be recruited after
activation by macrophages [66].
Whereas carious lesions are the most common cause for inflammatory reactions,
traumatic impact, for example, after crown fractures, may also expose the pulp to
the oral cavity and thus enable microorganisms to access the pulp chamber. In the
latter case, a healthy pulp can withstand bacterial invasion for several days. Animal
studies in monkeys demonstrated that the inflammatory zone did not extend more
than 2 mm into the pulp tissue even after 1 week of exposure to the oral cavity [67],
which highlights once more the remarkable ability of this tissue to withstand a bac-
terial attack.
Revitalization or regenerative treatment approaches in teeth with incomplete root
formation and pulp necrosis have become part of the therapeutic endodontic spec-
trum and should be considered as an alternative to conventional apexification.
Ideally, regenerative endodontic procedures allow not only for a resolution of pain,
inflammation, and periapical lesions, but also for the formation of an immunocom-
petent tissue inside the root canal which can reconstitute the original biological
structure and function of dental pulp and thus lead to an increase in root length and
thickness and strength of previously thin, fracture-prone dentin walls. Common fea-
tures of regenerative procedures performed in immature teeth with pulp necrosis
include (1) minimal or no instrumentation of the dentinal walls, (2) disinfection
with irrigant solutions, (3) application of an intracanal medicament, (4) provocation
of bleeding into the canal and creation of a blood clot, (5) capping with calcium sili-
cate, and (6) coronal seal. Next, we will discuss two strategies that have received
much attention recently for revitalization of necrotic young permanent teeth, i.e.,
stem cell homing and stem cell transplantation for dental pulp tissue engineering
(Fig. 20.1).
20 Biological Basis for Repair and Regeneration in Modern Endodontics and New… 361

Stem Cell Homing

Injection od Scaffold
+ Exogenous
Growth Factors
Composite
Restoration
Bioactive
Cement

Regenerated
Pulp

Stem Cells Stem Cells

Stem Cell Transplantation

Injection od Scaffold
+ Stem Cells
Composite
Restoration
Bioactive
Cement

Regenerated
Pulp

Stem Cells Stem Cells

Fig. 20.1 Schematic representation of two strategies for dental pulp tissue engineering. Stem cell
homing involves the injection of a cell-friendly scaffold and exogenous growth factors that induce
a chemotactic gradient for stem cells from the apical papilla to migrate toward the interior of the
pulp chamber and regenerate the dental pulp tissue. Alternatively, stem cells can be mixed in a
biodegradable scaffold and injected in the interior of the root canal. In this case, most of the regen-
erated pulp will be formed by the cells transplanted with more modest participation (if any) of the
stem cells from the apical papilla on the regeneration of the dental pulp
362 C. Cucco and J. E. Nör

20.4 Stem Cell Homing for Dental Pulp Tissue Engineering

Pulp vitality preservation is a major objective in endodontics, as devitalized teeth

are more vulnerable and prone to tooth loss later in life [68]. An adequate revascu-
larization is a determining element of success for dental pulp tissue engineering.
This is especially relevant when considering that the dental pulp tissue regeneration
takes place in a confined space with a sole access for nerve and vasculature supply
via the apical foramen. Application of the classic principles of tissue engineering
might allow us to better control the involved cells and tissues and lead to more pre-
dictable outcomes. Accordingly, the formation of new pulp in empty root canals was
shown in animal models by the insertion of scaffolds, cells, and growth factors [69].
This approach is challenged by several obstacles concerning translation and chair-
side application, namely, the availability of methods for isolation, storage, and
expansion of stem cells that follow good manufacturing practice guidelines.
Hence, cell homing (or in situ tissue engineering), i.e., the process in which a
primarily cell-free scaffold delivers bioactive cues to recruit resident stem cells and
induce their differentiation, has gained increasing attention recently [70]. In situ
tissue engineering has been investigated for various possible applications including
vascular grafts and nerve and hard tissue regeneration [71]. For in situ tissue engi-
neering (cell homing), the classic tissue engineering triad can be modified to resi-
dent stem cells, customized biodegradable scaffold that will promote timely
vascularization [72], and endogenous growth factors. Resident cell sources include
mesenchymal stem cells from dental pulp [1], apical papilla in immature teeth [47],
and the periapical area of teeth with complete root formation [60].
After disinfection, induction of bleeding into the root canal can lead to an influx
of stem cells from the apical papilla [73] and new tissue formation. Blood coagula-
tion results in the formation of a three-dimensional fibrin network containing not
only blood cells but also cytokines and growth factors that initiate wound healing
[57]. Those signaling molecules can promote chemotaxis, proliferation, and differ-
entiation of the stem cells inside the root canal and lead to generation of new tissue.
An extension of the respective protocol to mature teeth has been debated [74]. In
cases of immature and mature teeth, patients might benefit from less invasive and
regenerative-based treatment approaches in which tissue function is restored to
exert an immune response and generate a mineralized tissue barrier. Although cur-
rent clinical protocols show high success rates for this treatment [75, 76], histologic
analysis in animal studies [77] and occasional patient cases [78] show that pulp
tissue may not regenerate to its original architecture and function but rather repair
by the formation of fibrous tissue, cementum, or bone.
A recent study from Widbiller et al. (2018) demonstrated that fibrin-based mate-
rials enriched with endogenous, dentin-derived growth factors appear suitable for in
situ tissue engineering because they allow for cell ingrowth and pulp like tissue
formation. Currently used dental materials can also affect cell homing either indi-
rectly by stimulating the secretion of bioactive molecules by residual pulp cells or
directly by their chemical composition. For instance, conditioned medium of DPSCs
exposed to mineral trioxide aggregate and growth hormone induced endothelial
20 Biological Basis for Repair and Regeneration in Modern Endodontics and New… 363

tube-like formation and migration [79]. Furthermore, mineral trioxide aggregate

was shown to augment angiopoietin 1 and von Willebrand factor expression in
DPSCs [80].
Despite the developments of the last few years, dental pulp regeneration via cell
homing needs to be further understood and improved. Several aspects need to be
clarified to make it achievable and predictable in dental practices [81]. On the
whole, the comprehensive knowledge on cell homing for dental pulp regeneration
based on the most current literature considers the following:

• The importance of the scaffolds employed; further improvements are in progress,

such as nanofibrous technology and antibiotic addition [82].
• The efficacy of growth factors, especially when dentin-derived, as reported in the
latest update [69].
• The feasibility and safety of cell homing strategies in mature teeth with vital
pulps from animals and subsequently from humans, although better characteriza-
tion and standardization of the procedures are required [83].

20.5 Stem Cell Transplantation for Dental Pulp

Tissue Engineering

When the lost pulp tissue exceeds a critical size, cell homing may not be sufficient
to regenerate dentin-pulp tissue, and cell-based treatments may represent a more
desirable alternative approach. Considering the relatively ease of isolating dental
pulp stem cells (DPSCs) and their multipotential ability, most of the studies use
these cells for dental pulp regeneration purposes. Early studies in animal models
demonstrated that regeneration of pulp-like tissue was possible after stem cell trans-
plantation in tooth slices, dentin cylinders, and even whole tooth roots using a tissue
engineering concept [84–87]. Furthermore, animal models showed new tissue for-
mation in pulpotomies and in pulpectomies after stem cell transplantation [86, 88].
In another study, implantation of DPSCs and platelet-rich fibrin constructs in root
fragments in nude mice and in endodontically treated canine root canals led to more
pulp-like tissue generation with better vascularization as compared with DPSCs or
platelet-rich fibrin alone. This may be attributed to the slow release of growth fac-
tors from platelet-rich fibrin acting on the DPSCs [89]. Additionally, a study from
Li and colleagues (2016) demonstrated the benefit of combining DPSCs with a
VEGF-loaded microsphere-based scaffolding system for full-length human tooth
regeneration. The addition of DPSCs was necessary to regenerate blood vessels
throughout the entire root canal, which could be explained by DPSC-induced endo-
thelial cell migration and increased growth factor expression. Most recently, a mile-
stone was reached using autologous dental pulp stem cells transplanted into
permanent teeth with irreversible pulpitis [90]. In this study, a functional recovery
of pulp tissue was shown by detection of a new lateral mineralized tissue by cone-­
beam computed tomography. In a different study, autologous dental pulp stem cells
from deciduous canines were transplanted into permanent immature incisors in
364 C. Cucco and J. E. Nör

cases of pulp necrosis after dental trauma [91]. In this study, completion of root
formation was observed in the treatment group, which was not observed in the con-
trol group, where an apical plug was placed.
Animal and human studies provide some proof of principle that pulp tissue
regeneration can be achieved by the cell-based approach. However, in clinical prac-
tice several challenges have to be overcome, such as availability and isolation of
autologous stem cells, storage, expansion, culture, handling, maintenance of sterile
conditions, good manufacturing practice facilities, government regulatory policies,
and the clinician’s knowledge and skill.

20.6 Conclusions

Contemporary dentistry relies heavily on biomaterials to replace lost tissues in the

oral cavity. Such strategies restore shape and form but do not necessarily regener-
ate the physiological architecture and function of the lost tissue. Our understanding
of the biology of the pulp has improved significantly in recent years, and this has
allowed us to present more robust hypotheses regarding the molecular and cellular
processes responsible for dental regeneration. Thus, advances in the field of mate-
rial sciences, stem cell biology, and dental tissue engineering have raised the pos-
sibility of using biology-based treatment strategies developed to regenerate
functional dental tissues. Dental pulp stem cells are highly proliferative and have
the potential to differentiate into all the different cell types necessary to generate a
functional dental pulp. The high proliferation rates, self-renewal, multipotency,
and relative ease of access to tissues make the dental pulp an attractive source of
mesenchymal stem cells for tissue engineering. Compelling evidence pinpoints
that pulp tissue engineering after the transplantation of stem cells is possible.
However, severe problems regarding clinical feasibility remain. With that said, cell
homing is a potentially suitable alternative that may overcome those challenges.
However, the clinicians need to take into consideration that the success of pulp
regeneration relies on the clinical and biological conditions of the teeth. Hence,
cell homing strategies will not be consistently successful in every condition, such
as irreversible pulpitis and pulp necrosis. Root canal treatment remains the stan-
dard of care for mature teeth with necrotic pulps and closed apices. Despite such
issues, cell homing currently represents a path for dental pulp regeneration because
it recruits the patient’s own stem/progenitor cells through biological cues to restore
the lost and damaged pulp tissue. Stem cell homing and stem cell transplantation
for dental pulp tissue engineering might become clinically relevant strategies to
enable dental pulp regeneration in the future. However, the broad use of these tech-
niques will require more extensive clinical trials that demonstrate unequivocally
their safety and efficacy.
20 Biological Basis for Repair and Regeneration in Modern Endodontics and New… 365

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