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JDSR-244; No. of Pages 19 ARTICLE IN PRESS

Japanese Dental Science Review xxx (2020) xxx–xxx

Contents lists available at ScienceDirect

Japanese Dental Science Review

journal homepage: www.elsevier.com/locate/jdsr

Review Article

Current perspectives on dental adhesion: (1) Dentin adhesion – not

there yet
Jorge Perdigão
Professor, University of Minnesota, Department of Restorative Sciences, 515 SE Delaware St, 8-450 Moos Tower, Minneapolis, MN 55455, USA

a r t i c l e i n f o a b s t r a c t

Article history: The essential goal of any adhesive restoration is to achieve a tight and long-lasting adaptation of the
Received 5 June 2020 restorative material to enamel and dentin. The key challenge for new dental adhesives is to be simul-
Accepted 24 August 2020 taneously effective on two dental substrates of conflicting nature. Some barriers must be overcome to
accomplish this objective. While bonding to enamel by micromechanical interlocking of resin tags within
the array of microporosities in acid-etched enamel can be reliably achieved and can effectively seal the
restoration margins against leakage, bonding effectively and durably to organic and humid dentin is the
most puzzling task in adhesive dentistry.
Much of the research and development of dental adhesives has focused on making the clinical procedure
more user-friendly by reducing the number of bottles and/or steps. Although clinicians certainly prefer
less complicated and more versatile adhesive materials, there is a trade-off between simplification of
dental adhesives and clinical outcomes. Likewise, new materials are launched with claims of being novel
and having special properties without much supporting evidence.
This review article discusses dental adhesion acknowledging pioneer work in the field, highlights the
substrate as a major challenge to obtain durable adhesive restorations, as well as analyzes the three
adhesion strategies and their shortcomings. It also reviews the potential of chemical/ionic dental adhe-
sion, discusses the issue of extensively published laboratory research that does not translate to clinical
relevance, and leaves a few thoughts in regard to recent research that may have implications for future
adhesive materials.
© 2020 The Author. Published by Elsevier Ltd on behalf of The Japanese Association for Dental
Science. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/
licenses/by-nc-nd/4.0/).

1. Introduction When clinical studies are completed, often a new version of the
same material has already been made available on the market. In
Dental adhesion was responsible for a paradigm shift in den- fact, dental adhesives can be launched without proof of clinical
tistry (Table 1). Dental adhesives have become one of the most efficacy, as the FDA usually reviews “the Section 510(k) premar-
intriguing biomaterials in Health Sciences. Research efforts in the ket notification of intent to market the device and determines the
last 20 years have shifted from clinically-proven multi-step den- device to be substantially equivalent to legally marketed predicate
tal adhesives to simplified versions that do not perform adequately devices” used for the same indications [3–5].
in laboratory and clinical studies [1,2]. The ideal goals for clinical It is extremely difficult for practicing dentists to keep updated
effectiveness and durability of the restorations have been fre- as so many dental adhesives are constantly launched on the market
quently neglected in favor of fewer number of bottles and quicker and updated or relaunched within short periods of time. In addition,
application of newer dental adhesives. dentists do not have access to the latest evidence-based informa-
Several obstacles must be overcome to accomplish the objective tion. As a result, dentists rely on the information provided by the
of developing a dental adhesive that bonds effectively to enamel industry representatives or information disseminated in contin-
and dentin, and achieves durable restorations that seal the margins uing education courses and dental meetings, often without solid
and provide some form of resistance to recurrent caries lesions. evidence to support the claims [6].
The continuous development and frequent introduction of den- The objective of this review article is to summarize the current
tal adhesives render existing materials outdated within a few years. evidence on dental adhesion, from the challenging substrate to the
latest trends, many of which do not extrapolate to sound evidence
pertinent to clinical practice.

E-mail address: [email protected]

https://doi.org/10.1016/j.jdsr.2020.08.004
1882-7616/© 2020 The Author. Published by Elsevier Ltd on behalf of The Japanese Association for Dental Science. This is an open access article under the CC BY-NC-ND
license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

Please cite this article in press as: Perdigão J. Current perspectives on dental adhesion: (1) Dentin adhesion – not there yet. Japanese
Dental Science Review (2020), https://doi.org/10.1016/j.jdsr.2020.08.004
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Table 1
Changes that resulted from the introduction of adhesives in Dentistry.

Positive Negative

The use of dental adhesives has expanded across different dental disciplines Clinicians tend to rely solely on adhesion as the source of primary retention in
(Operative Dentistry, Orthodontics, Pediatric Dentistry, Periodontology, clinical situations without enamel margins or without enough residual tooth
Prosthodontics, Endodontics) structure, as in core build-up composite resin restorations
Dental adhesives are used to retain a wide range of restorative materials – Potential for marginal bacterial leakage when the cavo-surface margin is in
glass-matrix ceramics, oxide ceramics, pre-polymerized composite resins, dentin/cementum
direct composite resins, metal-based restorations, fiber posts, fiber splinting
materials
More conservative tooth preparations (lesion-specific preparations) Post-operative sensitivity in posterior adhesive restorations related to
polymerization shrinkage stress
Reliable micromechanical retention to etched enamel without Enamel cracks in posterior adhesive restorations related to polymerization
macro-retention features shrinkage stress
Reinforcement of residual tooth structure; undermined enamel does not need Moisture contamination of the operatory field may be more detrimental for
to be always removed adhesive than for non-adhesive restorations
Increased resistance to recurrent caries lesions when dentin is impregnated Small monomers, such as HEMA, may easily seep into the pulp space and cause
with dental adhesive pulp inflammation
Increased resistance to caries lesions in sealed fissure systems of posterior Frequent open contacts in posterior composite resin restorations (compared to
teeth amalgam restorations)
High efficacy to treat root sensitivity Adhesives may cause pulp necrosis if applied in preparations close to the pulp
Some adhesives have antibacterial properties, which may prevent recurrent Some of the monomers in dental adhesives may cause contact dermatitis
caries lesions
Stronger retention of glass-matrix ceramics restorations; adhesives increase
the resistance to fracture of glass-matrix ceramics
Stable chemical adhesion to hydroxyapatite for some adhesive materials when
dentin is not etched with phosphoric acid

2. Milestones in dental adhesion Etching enamel with phosphoric acid (Fig. 1) is still considered,
sixty-five years later, as the gold standard for bonding resin-based
In 1952, a manuscript published in the British Dental Jour- materials to tooth structure. The interlocking of resin tags (Fig. 1)
nal by Kramer and McLean described an in-situ study that was within the microsized porosities left by enamel chemical etch-
carried out in 124 preparations of 118 teeth scheduled to be ing can effectively seal the restoration margins in the long-term
extracted for orthodontic reasons [7]. The authors used 15 com- [13]. There is clinical evidence that dental adhesives result in more
binations of restorative materials. Tooth sections were stained reliable clinical behavior when enamel is etched prior to the appli-
with hematoxylin/eosin upon extraction, and observed blindly cation of the adhesive [14]. Nonetheless, new adhesives are still
under the optical microscope. The authors then matched the being launched without recommendations for etching enamel with
data with the experimental groups. Some of the sections dis- phosphoric acid.
played “an altered reaction observed as a narrow zone of material Another milestone in adhesive dentistry occurred in 1960.
staining deeply with hæmatoxylin immediately bordering the cav- Rafael Bowen (who retired from the ADA Foundation Research
ity. This zone averaged about 3 m in thickness and was seen to Center in 2018 after 62 years of continuous service) and Mario
be composed of dentine having an intense affinity for hæmatoxylin. Rodriguez presented a paper [15] at the IADR meeting in Chicago
This change was present in all of the 28 teeth filled with Sevriton- that reported the tensile strength of several materials, including
adhesive. Similar changes were absent from all of the 96 teeth filled a new silica-resin material that contained “about 70 per cent vinyl
with other materials.” The specific chemically-cured adhesive used silane-treated clear fused silica combined with about 30 per cent of an
in this study had been developed in 1949 by Oskar Hagger, a adduct of glycidyl methacrylate and bisphenol A”. It is worth under-
chemist who worked for DeTrey/Amalgamated Dental Company lining here the inclusion of a silane to bond the inorganic filler to the
[8]. The adhesive contained a phosphate monomer, later identi- new Bis-GMA resin. By 1963, the full composition of the new mate-
fied by Dr. Buonocore’s research group as glycerol phosphoric acid rial had been finalized [16]. Based on Bowen’s research with the
dimethacrylate [9], which is still used in a few dental adhesives Bis-GMA molecule, the first commercial composite resin (Addent,
as GPDM [10]. Remarkably, the findings of the 1952 manuscript 3 M) was introduced in 1964 as a chemically-cured paste-paste
[7] were the first reference to the concept currently known as material. Interestingly, since that time most changes in composite
the hybrid layer, elegantly illustrated with an image of dentin resin technology have been in the filler particle size and distribu-
altered by the adhesive [7]. In addition, the use of the phosphate tion rather than in the resin matrix, which is still based on Bis-GMA,
monomer GPDM as a dentin adhesive may now be part of history also known as Bowen’s resin.
as the first research report of a self-etch adhesive in the litera- Alan Wilson and Brian Kent, working at the Laboratory of the
ture. Government Chemist in the UK, invented in 1968 one the most
In 1955, a major advance for the history of dental adhesion was groundbreaking materials in dentistry, for which the patent was
published in the Journal of Dental Research [11]. Michael Buono- applied for in 1969 [17]. This self-adhesive material was widely
core used 85% phosphoric acid to change enamel surfaces and make known as glass-ionomer cement (GIC), although the correct ter-
them more suitable for mechanical adhesion, using an industrial minology is glass polyalkenoate cement [18]. The first report of
technique that improved the adhesion of paints to metal surfaces. their findings in the literature appeared in 1971 [19]. The commer-
Buonocore later expanded his acid-etch technique to clinical den- cial version was subsequently launched in Europe in 1975 under
tistry to seal pits and fissures, as reported in 1967 [12]. The authors the commercial name ASPA by Amalgamated Dental International,
used 50% phosphoric to etch pits and fissures, followed by the appli- DeTrey Division.
cation of a silica-filled methacrylate adhesive. This novel technique, Takao Fusayama, defying the general belief that etching dentin
which was not standard of care in 1967, resulted in a reduction of caused irreversible pulp damage, in 1979 reported that etching
caries incidence in pits and fissures by as much as 86.3% at 1 year dentin and enamel with 40% phosphoric acid for 60 sec substan-
[12]. tially improved the adhesion of Clearfil Bond System-F (Kuraray)

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Fig. 1. (a) SEM micrograph of human enamel etched with 35% phosphoric acid for 15 s. Original magnification = 5,000X. (b) SEM micrograph of a replica of an interface of
etched enamel with a dental adhesive. After curing the adhesive, the specimen was left in 6N HCl for 12 h to dissolve the enamel. The enamel prisms at the interface were
not dissolved because the etched enamel was impregnated with polymerized adhesive, creating a hybrid layer. H – hybrid layer; Ad – adhesive; E – residual enamel. Original
magnification = 5,000X.

[20]. For the first time, the concept of “total-etch” was associated interlocking of resin monomers into the array of microporosities
with improved dentin adhesion. left by the acid chemical dissolution of enamel (Fig. 1). Bonding to
Nobuo Nakabayashi’s research team was responsible for another enamel after etching with phosphoric acid is certainly the founda-
breakthrough in 1982, when they reported for the first time tion for the durability of adhesive restorative procedures.
a “demineralization-resistant zone” [21] in dentin after etching Dentin is a complex biocomposite structure, defined by some
dentin with 10% citric acid-3% ferric chloride (10:3 solution) for authors as a puzzle of different types of dentin and by other authors
30 sec and applying 4-META (methacryloxyethyltrimellitate anhy- as a bone-like nanocomposite built of carbonated hydroxyapatite
dride) cured with tri-n-butyl borane. This concept of hybrid layer mineral particles, protein, and water [24,25]. As opposed to enamel,
in etched dentin was identified using the scanning electron micro- dentin is a humid and more organic substrate. Dentin adhesion
scope (SEM). The same authors also highlighted the importance of has been one of the most challenging and less predictable tasks
monomers with both hydrophobic and hydrophilic groups to pro- in adhesive dentistry due to the dynamic compositional differences
mote adhesion with tooth substrates by penetration and infiltration and complex histology of dentin. The ability of adhering restorative
dentin as a new concept in biocompatible materials for dental use materials intimately to dentin is affected by many factors, includ-
[21]. ing biological and clinical factors. These factors include the patient’s
The most recent milestone was associated with the adhesion- age, location of the tooth in the mouth, dentin depth and perme-
decalcification concept (AD-concept) for adhesion to dentin ability, pulpal fluid flow, presence of sclerotic and/or carious dentin,
[22,23]. This concept was originally described for carboxylic acids. radicular versus coronal dentin, type of restorative material and
When these acids are applied on hydroxyapatite they first form procedure, isolation, parafunctional habits, dentist’s experience,
ionic bonds to calcium, which may be dependent on the pKa of among others [26–31].
each acid. While some of the carboxylic acids, such as oxalic acid, The mineral phase (hydroxyapatite) of dentin is on average
stay attached to calcium on the hydroxyapatite surface resulting 45 vol%, while the organic matrix is 33 vol%, the remainder being
in insignificant decalcification, other carboxylic acids result in a water [32]. Type I collagen is the most abundant protein in the
significant decalcification of hydroxyapatite with minimal or no organic phase. Dentin encloses a maze of inverted-cone shaped
chemical attachment. This adhesion-decalcification (AD) concept is tubules that traverse dentin, radially oriented with the larger diam-
still relevant. Etch-and-rinse (ER) adhesives follow the decalcifica- eter facing the pulp [26]. Garberoglio and Brännström in 1976 [33]
tion pathway derived from phosphoric acid etching, whereas mild measured the area occupied by the tubules and the tubular diam-
self-etch (SE) adhesives (pH ≈ 2), such as those that contain 10- eter in 30 extracted teeth. The number of tubules near the pulp
methacryloyloxydecyl dihydrogen phosphate or 10-MDP (MDP), was 45,000 per square millimeter and their diameter 2.5 ␮m. In
tend to follow the adhesion pathway. Nevertheless, mild SE adhe- middle dentin, the number of tubules was 29,500/mm2 and the
sives still cause minimal decalcification, which is still required for average diameter was 1.2 ␮m. In superficial dentin, the area occu-
calcium release and subsequent formation of stable MDP-Ca salts pied by tubules was 20,000/mm2 and the average tubule diameter
and respective nanolayering, as discussed later in this article. was 0.9 ␮m [33]. The contents of water increase 20-fold from super-
ficial to deep dentin. The mean tubule volume in coronal dentin is
10% of the entire dentin volume, while near the DEJ it is 4% and
3. The substrate increases to 28% near the pulp [33] (Fig. 2).
Dentin tubules are permeated with fluid under constant out-
Enamel and dentin are the dental substrates to which we bond ward pulpal pressure estimated to be 25 to 30 mm Hg [34]. In
our restorative materials. Cementum may also be involved when addition, there is fluid present within the intertubular dentin
the cavo-surface margin is located apically to the cementum- area, making dentin an intrinsically moist hard tissue throughout
enamel junction. its internal structure. Dentin contains extensions of the odonto-
Enamel is a dry substrate without vital structures containing blast (odontoblastic processes) and intra-tubular collagen fibers
92 vol% of mineral phase (hydroxyapatite), which makes enamel in deeper areas (Fig. 3), less frequently in middle and superficial
almost the ideal substrate to form a tight adhesive joint. The dentin. These characteristics, which we sometimes overlook as clin-
acid-etch technique [11] is still the gold standard for bonding icians, attest the greater challenge when an adhesive restoration is
resin-based materials to tooth structure. The micromechanical inserted in deep dentin compared to restorations placed in more
interaction of adhesives with enamel is a result of the diffusion and superficial dentin.

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Fig. 2. (a) SEM micrograph of fractured superficial dentin. Int – intertubular dentin; P – peritubular dentin; T – dentin tubule; Arrows – bacteria in the tubule lumen. Original
magnification = 10,000X. (b) SEM micrograph of fractured deep dentin 75 ␮m from the pulp of the same tooth in Fig. 2a. Original magnification = 10,000X.

Fig. 3. (a) SEM micrograph of fractured middle dentin showing an odontoblastic process extending from the tubule Int – intertubular dentin; P – peritubular dentin; T –
dentine tubule. Original magnification = 10,000X. (b) SEM micrograph of fractured deep dentin showing intratubular collagen (asterisk) with the characteristic 64 nm collagen
banding pattern. Int – intertubular dentin; P – peritubular dentin; T – dentin tubule. Original magnification = 25,000X.

Fig. 5. Non-carious cervical lesion (NCCL) with sclerotic dentin.

Fig. 4. SEM micrograph of fractured dentin-enamel junction (DEJ) area. Note the
morphological differences between enamel and dentin hydroxyapatite. Original
magnification = 5,000X. Arrows – DEJ; E – enamel; Int – intertubular dentin; T – ical bonding to dentin is facilitated by the smaller size and the
dentin tubule. crisscross orientation of the hydroxyapatite crystallites [35]. The
different crystallite size facilitates chemical bonding to dentin to
In addition to the compositional differences, there is a subtle the detriment of chemical bonding to enamel [35].
difference between the enamel and dentin hydroxyapatite crys- Physiological changes resulting from dentin aging or in response
tallites. Enamel crystallites are larger and have a more regular to carious lesions and other aggressive stimuli increase the degree
and parallel oriented arrangement, whereas dentin hydroxyapatite of mineralization of dentin, resulting in an increase in dentin thick-
crystals are smaller and arranged in a crisscross pattern within ness and a reduction of dentin permeability [28,29]. Reduction of
the organic matrix (Fig. 4), rendering it more difficult to establish permeability with age may have a direct effect on dentin bond
a micro-mechanical interlocking with dentin. Conversely, chem- strengths [36] as dentin permeability affects the adhesion process.

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Fig. 6. Sequence of SEM micrographs to illustrate the morphological characteristics of the bonding substrate in a NCCL of a recently extracted mandibular canine. (a) SEM
micrograph depicting a general view of the NCCL. The incisal aspect is on the right side (E-enamel), with the cervical aspect on the left side (R-root). The white arrows point
to the natural incisal cavo-surface margin. The dark arrows point to the natural cervical cavo-surface margin. Original magnification = 30X. (b) SEM micrograph of the area
included in the rectangle in Fig. 6a. The horizontal dotted line separates the unetched area (upper half) from the area that was etched with 35% phosphoric acid for 15 s
(lower half). Original magnification = 100X. (c) SEM micrograph of the area included in the rectangle of Fig. 6b (etched area). Note the sclerotic casts in the tubules (circles)
and, overall, hypermineralized dentin. Original magnification = 1,000X. (d) SEM micrograph of a sclerotic cast (asterisk) obliterating the tubule (T). Note how intertubular
dentin (Int) is densely mineralized. Original magnification = 15,000X. (e) SEM micrograph of bacteria (arrows) ‘fossilized’ into the mineralized area of intertubular dentin
(Int). Original magnification = 15,000X. (f) SEM micrograph of a longitudinal fracture of dentin in a NCCL. Note how the tubule is obliterated with rhombohedral mineral
crystals, which were elegantly described in 1989 [173]. Int – intertubular dentin; P – peritubular dentin; T – dentin tubule. Original magnification = 15,000X.

4. Relevance of in vitro testing for dental adhesion ious dentin area. Affected dentin is slightly decalcified but sill
amenable to recalcification, with odontoblastic processes, sound
Several peer-reviewed publications have covered this topic collagen fibers, and apatite crystals bound to the fibers [40,41].
very well [37–39]. It is still important to emphasize that labora- Continuous deposition of mineral within the tubules underneath
tory tests of dental adhesives usually employ extracted impacted a carious lesion process results in tubular obliteration and the
third molars and premolars extracted for orthodontic reasons. This formation of sclerosis, and potentially reducing bond strengths
‘laboratory-type’ (or unaffected dentin substrate) lacks clinical rel- [28].
evance, as clinicians place adhesive restorations in teeth that have Another type of clinically relevant dentin that may be found in
had carious lesions, failed restorations, or non-carious cervical deep caries lesions is reactionary tertiary dentin, which is formed by
lesions with sclerotic dentin continuously exposed to the oral envi- odontoblasts in the pulp chamber wall near the area corresponding
ronment. to the carious lesion or to the occlusal trauma. In case of a pulp expo-
The clinically relevant substrates for dentin adhesion include sure, newly differentiated odontoblast-like or odontoblastoid cells
affected dentin, which is located immediately underneath the car- replace the irreversibly injured odontoblasts at the exposure site

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Table 2
Classification of dental adhesives by adhesion strategy.

Etch-and-rinse (ER) 3-step ER

Ac + Pr + BR

2-step ER Ac + (Pr/BR)

Self-etch (SE) 2-step SE

No separate etchant (Ac/Pr) + BR

1-step SE Universal adhesives used

(Ac/Pr/BR) as SE adhesives

Self-adhesive (SA) Composite resin Adhesive and

No separate adhesive GICs, including RMGICs restorative are the
(pre-conditioning with PAA) same material

Ac – Phosphoric acid; Pr – Hydrophilic primer; BR – Non-solvated bonding resin; GIC– glass ionomer cement; PAA -polyacrylic acid.

and form a bridge of atubular dentin known as reparative tertiary ponents of the dental adhesive, i.e., etchant, primer and bonding
dentin [42]. resin.
Sclerotic dentin is common in areas where dentin has been
exposed to the oral environment, such as non-carious cervical II By adhesion strategy – with or without etching enamel and
lesions (NCCLs) (Fig. 5). These lesions contain a complex dentin dentin simultaneously with phosphoric acid (Table 2).
substrate with different ultrastructural layers [43], including a
hypermineralized layer on the surface with denatured collagen This classification is easier to understand for practicing den-
and bacteria (Fig. 6). The tubules appear obliterated by crystalline tists than the classification by generation, as adhesives are grouped
deposits. Etching sclerotic dentin in NCCLs is difficult to achieve according to their interaction with the tooth structure, more pre-
[43,44], as phosphoric acid does not etch underneath the hyper- cisely according to the way they interact with the smear layer
mineralized surface layer and is unable to dissolve the sclerotic (Fig. 7a). In addition, it is informative in regards to the differ-
casts in the tubules. Due to the intricacies of the substrate, restora- ent steps used in the adhesive procedure. This nomenclature will
tions of NCCLs have a higher tendency to fail than restorations in be used in this manuscript (Table 2). Adhesives that include a
other areas of the mouth [43,45]. Roughening the superficial area phosphoric acid-etching step are known as etch-and-rinse (ER)
of hypermineralized dentin (and enamel) in NCCLs improves the adhesives. They dissolve and remove the smear layer and smear
survival rate of restorations [46]. plugs (Fig. 7b). Adhesives that do not use a separate etching step
are known as self-etch (SE) adhesives, as they do not remove the
smear layer, but incorporate into the adhesive interface (Fig. 7c).
5. Current dental adhesives
Self-adhesive (SA) materials (dental adhesive and restorative com-
Dental adhesives are currently categorized using two different ponent all-in-one material), belong to another strategy for adhesion
classifications. to tooth structure, as either composite resins or GIC-based materi-
als. The latter use a separate polyalkenoic acid (often polyacrylic)
dentin conditioner that is rinsed off (Fig. 7d).
I By generation – from first to eighth generations. The basic components of a dental adhesive system are

It is used mostly by the dental industry to highlight the latest A) Etchant, currently phosphoric acid in a concentration between
trend. It is a confusing nomenclature, as the first dentin adhe- 30% and 40%. Most phosphoric acid gels are thickened with sil-
sives that used a phosphoric acid etchant on enamel and dentin ica microparticles, although there are a few that contain other
are known as the fourth generation. This classification is not very thickeners such as xanthan gum. A color dye is always included
informative either, especially when considering the missing com- to improve the application accuracy and ensure that all gel is

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Fig. 7. (a) SEM micrograph of a fractured human dentin specimen with smear layer and a smear plug created with diamond bur. Int – intertubular dentin; P – peritubular
dentin; T – dentin tubule; Sp – smear plug; Oc –occlusal surface; Dotted circle – another tubule plugged with smear layer. Original magnification = 10,000X. (b) SEM
micrograph of human dentin etched with liquid phosphoric acid for 15 sec. Int – intertubular dentin; P – peritubular dentin; T – dentin tubule; Oc – occlusal surface; Pc –
exposed peritubular collagen from dissolution of the peritubular dentin; Dd – dentin demineralized by the etching agent; arrows – other tubules. Original magnification =
10,000X. (c) SEM micrograph of human dentin treated with the Clearfil SE primer (Kuraray) from the 2-step SE adhesive Clearfil SE Bond. The asterisk marks the area of dentin
partially decalcified by the primer (pH = 1.8–2.0). Upon application of the respective hydrophobic bonding resin, this 0.5 ␮m deep area will become the hybrid layer. Int –
intertubular dentin; T – dentin tubule; Oc – occlusal surface; Sp – primer-infiltrated smear plug. Original magnification = 15,000X. (d) SEM micrograph of occlusal view of
human dentin treated with GC Cavity Conditioner (20% polyacrylic acid with 3% aluminum chloride hexahydrate) for 10 sec, and rinsed with water for 15 sec. Note residual
smear layer (ovals) and some patent tubules (T). The intertubular dentin does not have morphological characteristics of demineralization (no visible collagen fibers). Original
magnification = 5,000X.

Table 3
Etch-and-rinse adhesives.

Advantages Disadvantages

Three-step ER adhesives have been available since the 1990s, therefore they Acetone-based adhesives need more applications than those recommended by
have a long-track record. the respective manufacturers [51].
High immediate dentin and enamel bond strengths in laboratory studies Over-etching decreases bond strengths [52].
Excellent bonding to enamel in vitro and durable restorations in clinical More technique sensitive than SE adhesives, as the potential for incomplete
studies. However, retention rates for 2-step ER adhesives are lower than for infiltration of the adhesive into the etched dentin depends on several
3-step ER adhesives [49]. contributing factors occurring simultaneously in a very short time.
Clinical studies over 5 years with excellent results for specific 3-step ER Hydrolytic degradation of the bonds occurs when margins are located in
adhesives. Optibond FL (Kerr) resulted in excellent retention at 13 years in dentin.
NCCLs [50]. Optibond FL is still the reference against which all ER adhesives
are compared.
As these adhesives contain organic solvents such as ethanol or acetone, minor The clinical and in vitro performance of 2-step ER adhesives undergo
dentin contamination with saliva does not always decrease bond strengths degradation faster than that of 3-step ER adhesives.
in vitro.
As opposed to 2-step ER adhesives, 3-step ER adhesives contain a hydrophobic Bond strengths may vary with the degree of moisture, depending on the
bonding resin that prevents or delays the degradation of the resin-dentin specific adhesive.
interface by making the interface impermeable and increasing the film
thickness. The lack of solvent increases the degree of conversion.
ER adhesives may result in mechanical interlocking with etched dentin Although clinical evidence demonstrates that ER adhesives do not cause more
provided that the dentin in not overetched, the primer/adhesive for 2-step post-operative sensitivity than SE adhesives [53,54], some clinicians claim that
ER adhesives is applied in an active scrubbing mode, and that there is not ER adhesives cause higher incidence of post-operative sensitivity with
excessive water within the interfibrillar spaces. posterior composite restorations.
Ability to bond composite, porcelain, fiber posts, etched or sandblasted metals, Solvent air-drying time recommended by the manufacturers is insufficient
or amalgam. [55] and must be extended.

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Table 4
Median intertubular dentin demineralization of current phosphoric acid gels [56].

Etching gel Intertubular dentin

demineralization (␮m)
Etching time =15 sec

Ultra-Etch 35% 1.155A

(Ultradent)
Scotchbond Universal Etchant 32% 1.675AB
(3 M Oral Care)
Tooth Conditioning Gel 34% 2.185B
(Dentsply Sirona)
Total Etch 37% 2.820C
(IvoclarVivadent)
Select HV Etch 35% 3.090C
(Bisco)
Scotchbond Etchant 35% 3.205C
3 M Oral Care)
Gel Etchant 37.5% 4.033D
(Kerr)
Liquid etchant 35% 4.636D
Fig. 8. TEM micrograph of the adhesive-dentin interface formed by the 3-step (prepared in laboratory)
ER adhesive OptiBond FL (Kerr). The particle-filled hydrophobic bonding adhesive
Three dentin disks per etching gel; 4 measurements in each half disk in identical
resulted in filled resin tags (Rt). Ad – adhesive; H – hybrid layer; D – dentin. Original
areas, 24 measurements per etching gel; measurements taken with image analysis
magnification = 6,000X.
software (ImageJ, NIH). Statistical analysis included Kruskal-Wallis and Median tests
at p < 0.05
washed off. Glycol is often added to improve wettability and
decrease viscosity. The etchant is always rinsed off from the
tooth surface.
B) Primer which is a hydrophilic solution of resin monomers, (Table 4) without reducing dentin bond strengths. However, their
organic solvent (alcohol or acetone), water, and stabilizers. The effect on enamel bonding durability needs to be further investi-
hydrophilic groups boost the wettability to the dentin surface, gated.
which is a humid environment. The role of primers in dentin Since the early 1990s, the concept of wet or moist dentin for ER
adhesives is comparable to that of primers in paints. The primer adhesives [60,61] has been widely advocated and taught in den-
adheres to surfaces and forms a binding layer that is better pre- tal schools. The collagen left in the area of demineralized dentin
pared to receive the paint, in this case, the bonding resin. Primers collapses when dentin is air-dried after rinsing off the etchant.
are not usually rinsed off nor cured once placed on the tooth This collapse results in incomplete infiltration of the adhesive into
surface; they are only air-dried.’ demineralized intertubular dentin [62] and lower bond strengths
C) The bonding resin is a solvent-free (hydrophobic) low-viscosity [63]. For this reason, keeping the dentin substrate moist (glis-
resin that is applied over the primer and then light-cured. The tening) after rinsing off the etching gel has been recommended
hydrophobic groups interact and copolymerize with the restora- based on in vitro testing. However, in vitro tests are carried out in
tive material and make dentin bonding more stable and more “laboratory-type” or unaffected dentin, as discussed above. When
durable by sealing the bonded interface against nanoleakage the degree of dentin moisture was tested in clinical trials with
[47,48]. The hydrophobic resin improves both the polymeriza- the same or similar ER adhesives, including a recent study with
tion rate of the primer and the mechanical properties of the a universal adhesive, moist dentin was not associated with bet-
adhesive and hybrid layer [48]. Adhesive systems that have this ter retention rate for ER adhesives when compared to dry dentin
separate bonding step result in better in vitro and clinical out- [64,65].
comes [49]. Leaving the dentin moist after etching and rinsing may not be so
crucial with current simplified adhesives, as agitation of the adhe-
Dental adhesives may involve three separate procedures or sive during application improves infiltration of the monomers into
steps, two of them merged in one, or all of them merged in one etched dentin. In fact, a clinical study in non-carious cervical lesions
(Table 2). (NCCLs) found that passive application of the adhesive resulted in
82.5% retention rate after 2 years compared to 92.5% retention rate
5.1. Etch-and-rinse (ER) adhesives of the restorations in which the adhesive was scrubbed vigorously
[66]. Furthermore, leaving dentin moist has been shown to cause
The advantages and disadvantages of ER adhesives ae summa- degradation of the resin dentin interfaces at 6 months [67]. Den-
rized in Table 3. The first ER adhesives were 3-step adhesives. They tists are advised to gently dry dentin after rinsing off the gel without
include an acid etchant applied to enamel and dentin simultane- inducing desiccation.
ously to remove the smear layer and demineralize the substrate. In addition, the residual water inside the resin-adhesive inter-
Phosphoric acid has been the standard etchant but other acids face reduces the degree of conversion of the monomers and may
have been unsuccessfully used, namely maleic, nitric and oxalic induce hydrolytic degradation of adhesive polymers, compromis-
acids [57–59]. The 3-step ER adhesives also include a primer ing their physical properties [68–70]. Once the resins that envelope
and a hydrophobic bonding resin that infiltrates the demineral- the collagen fibers are dissolved, the fibers become susceptible to
ized dentin (Dd in Fig. 7b) to form a hybrid layer of collagen further degradation [48]. A simple method to remove the extra
and resin (Fig. 8). Regarding the phosphoric acid etching agent, water from the adhesive interface is to extend the solvent drying
the current market tendency is for newer gels (Fig. 9a) being time. The 5 to 10 sec duration usually recommended by manufac-
less viscous (runnier) than older phosphoric acid gels (Fig. 9b), turers may be inadequate to obtain durable bonding to dentin. as
which is likely to be as a result of extra glycol added to the gel. discussed under universal adhesives [55,71]. Gently air drying for
Although this detail is often overlooked, newer gels are much at least 15 seconds is recommended for simplified adhesives with
less aggressive on enamel and dentin than their predecessors [56] water in their composition.

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Fig. 9. (a) SEM micrograph of human dentin etched with 32% phosphoric acid (Scotchbond Universal Etchant, 3M). Original magnification = 7,000X. (b) SEM micrograph
of human dentin etched with 35% phosphoric acid (Scotchbond Etchant, 3M). Original magnification = 7,000X. Int – intertubular dentin; P –peritubular dentin; T – dentin
tubule; Oc – Occlusal surface; Pc – exposed peritubular collagen from dissolution of the peritubular dentin; Dd – dentin demineralized by the etching agent; Circles – silica
thickening agent; Arrows – intertubular anastomoses.

Fig. 10. (a) TEM micrograph of the adhesive-dentin interface formed by the 2-step SE adhesive OptiBond SE (Kerr). Hydroxyapatite crystals are visible inside the entire
length of the 1 ␮m-thick hybrid layer (dotted circle). Int – intertubular dentin; T – tubule; Ad – adhesive; Cr – composite resin; H – hybrid layer. Original magnification
= 12,000X. (b) TEM micrograph of the adhesive-dentin interface formed by the 1-step SE adhesive G-ænial Bond (GC), a HEMA-free adhesive. Hydroxyapatite crystals are
mixed with smear layer remnants in the 0.4 ␮m-thick hybrid layer. Int – intertubular dentin; T – tubule; Ad – adhesive; H – hybrid layer; SP – smear plug. Arrows – empty
areas corresponding to droplets in the transition between the adhesive layer and the hybrid layer. Original magnification = 40,000X.

5.2. Self-etch (SE) adhesives

The advantages and disadvantages of SE adhesives are sum-

marized in Table 5. The first SE adhesives were 2-step adhesives.
They included an acidic primer and a hydrophobic bonding resin
(Table 2). As SE adhesives do not require separate acid-etching and
rinsing steps, they condition and prime enamel and dentin simul-
taneously, relying on their ability to infiltrate through smear layers
(Fig. 7c) and partially dissolve hydroxyapatite to generate a hybrid
layer with residual hydroxyapatite crystals [1] (Fig. 10). One of the
positive features of SE adhesives is that they are considered more
user-friendly than ER adhesives because their application time is
somewhat reduced. A crucial shortcoming is their incapacity to
etch enamel adequately, as they result in a poorly-defined shal-
low enamel etching pattern. However, the enamel etching pattern
Fig. 11. Selective enamel etching with 35% phosphoric acid in an occlusal prepara-
produced by the SE adhesives depends on their acidity, applica-
tion of a mandibular molar.
tion time, and application mode [72,73]. The poor etching ability of
self-etch adhesives may result in debonding at the margins, leading
to marginal discoloration. A simple way to improve the bonding The pH of the SE adhesive priming solution is the basis for cate-
of SE adhesives is to etch enamel without etching dentin, which gorizing them as ultra-mild (pH ≥ 2.5), mild (pH ≈ 2), intermediately
is known as the “selective enamel etching” technique (Fig. 11). A strong (pH between 1 and 2) and strong (pH < 1) [2]. Mild self-etch
systematic review of clinical trials of up to 3 years showed that adhesives partially dissolve dentin to a depth under 1 ␮m, leav-
selective enamel etching resulted in less marginal discoloration, ing behind a significant amount of hydroxyapatite crystallites to
better marginal integrity, and increased retention rate of composite interact with functional monomers in the adhesive (Fig. 10). The
restorations bonded with SE adhesives [14]. adhesion mechanism in this case is two-fold: (A) Micromechanical

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Table 5
Self-etch adhesives.

Advantages Disadvantages

Extremely easy to apply, no etching, no rinsing. The acidic primer is not as acidic as phosphoric acid; therefore, SE adhesives
do not etch enamel to the same depth as phosphoric acid.
SE adhesives can be used with selective enamel etching to improve clinical Some 1-step SE adhesives need more applications than those recommended
performance. by the respective manufacturers [76,77]
At least one 2-step SE adhesive has been available since the late 1990s, Some 1-step SE adhesives result in clinical signs of enamel leakage at 1 year,
therefore they have a long-track record. and unacceptable marginal discoloration at 2 years [78]
Mild SE adhesives result in a sub-micrometric resin-infiltrated calcium-rich The acidity of 1-step SE adhesives inhibits the polymerization of
hybrid layer allowing for simultaneous micromechanical and chemical chemically-cured composites. Special attention may be required to the
bonding. utilization of self- or dual-cure cured composite buildup materials and self- or
dual-cured luting cements with 1-step SE adhesives.
Two-step SE adhesives (for example, Clearfil SE Bond, Kuraray Noritake) On dentin 1-step SE adhesives behave as permeable membranes after
contain a hydrophobic bonding resin that prevents or delays the degradation polymerization, allowing the permeation of fluids through the adhesive layer
of the resin-dentin interface. to the surface and subsequent degradation of the resin-dentin interface by
hydrolysis.
The inclusion in their composition of monomers capable of bonding On enamel, HEMA-free 1-step SE adhesives result in the formation of water
chemically to calcium, such as MDP, has been shown to be a major blisters or droplets on the surface of the adhesive, which may compromise
breakthrough for the durability of adhesive restorations. durability of enamel bonding.
Clearfil SE Bond (Kuraray Noritake) results in high dentin bond strengths One-step HEMA-free self-etch adhesives undergo phase separation in the form
in vitro [74] and excellent clinical results at 13 years [75]. Clearfil SE Bond is of droplets, while HEMA-rich 1-step adhesives may result in droplets in the
still the reference against which all other SE adhesives are compared. adhesive layer induced by osmosis.
One-step SE adhesives are available in unidose to help complying with stricter Residual water (from their composition) may become entrapped if not
infection control guidelines in some countries. properly evaporated, which results in nanoleakage.
Strong 1-step SE adhesives result in enamel bond strengths comparable to ER
adhesives, but cause a deep dentin decalcification similar to that of ER
adhesives, which results in poor bonding to dentin [77,79]. Nevertheless, a few
clinical studies up to 3 years have reported excellent retention in spite of the
marginal degradation [80,81].

entanglement of the adhesive with the partially decalcified dentin micromechanical retention [84]; (C) The presence of the hydropho-
to form a sub-micrometric hybrid layer; (B) Chemical/ionic inter- bic bonding resin, which prevents the degradation of the adhesive
action of functional monomers, such as phosphate or carboxylate, interface, as discussed above.
with calcium in hydroxyapatite.
The dentin and enamel etching pattern of strong SE adhesives
resembles that of ER adhesives (Fig. 12). While this is a posi- 5.3. Simplification versus effectiveness
tive feature for enamel bonding, it has the opposite effect on
dentin adhesion. Strong SE adhesives remove hydroxyapatite that The 3-step ER adhesives and 2-step self-etch adhesives (Table 2)
is potentially needed for chemical bonding of functional monomers have been shown to be clinically effective over time [49,75,85]. To
to dentin. In addition, 1-step SE adhesives contain at least 20% make the bonding procedure easier and faster, manufacturers have
water [82], which is required to ionize the respective monomers merged some of the three steps, i.e., etchant, hydrophilic primer and
and enable the monomers to interact with enamel and dentin. As hydrophobic bonding resin. There is strong clinical evidence that the
strong 1-step SE adhesives demineralize dentin as deep as some trend for simplification of the dentin bonding procedure results
phosphoric acid etchants (Fig. 12b), the complete evaporation of the in lower effectiveness and compromised durability. For example,
water from the adhesive inside the demineralized dentin is unlikely 2-step ER adhesives do not have a separate primer and bonding
to occur in a clinical setting. In addition, being SE adhesives, they resin. They have a solution that is a blend of both, therefore com-
do not include a rinsing step, which may lead to accumulation of bining hydrophilic and hydrophobic monomers in the same bottle.
precipitates from the dissolution of hydroxyapatite within or above Unfortunately, the lack of a separate hydrophobic bonding layer in
the hybrid layer. This was the case of Prompt L-Pop (pH ≈ 1), orig- 2-step ER adhesives makes the resin-dentin interfaces more sus-
inally marketed by ESPE and later introduced in different versions ceptible to in vitro and clinical degradation. As a result, the clinical
by 3 M ESPE. The shortcomings described above may have resulted outcomes of 2-step ER adhesives are worse than those of their pre-
in clinical failure rates of this specific adhesive of 35% at 1 year [83]. decessors, the 3-step-ER adhesives [49]. Another example is the
The difference between 1-step SE and 2-step SE adhesives is the simplification from 2-step SE to 1-step SE adhesives. The omission
extra hydrophobic bonding resin applied over the acidic primer for of the hydrophobic bonding resin in 1-step SE adhesives makes
2-step SE adhesives (Table 2). A 2-step SE adhesive is currently the them more vulnerable to in vitro degradation and poor clinical per-
gold standard for the SE strategy. Clearfil SE Bond (Kuraray Noritake) formance [47,49,78,86–89].
has resulted in excellent 13-year clinical retention rates in NCCLs Some simplified adhesives, including 2-step ER and 1-step SE,
[75], more specifically, 86% for SE and 93% for selective enamel etch. are advertised as being easy and quick to use. Yet, several of them
This adhesive was first launched in Japan in the late 1990s as Mega need more coats than those recommended by the respective manu-
Bond (Kuraray) therefore it has a long track record of over 20 years. facturer [51,76,77], making the respective clinical application more
Three factors may be responsible for the excellent clinical time-consuming than their less simplified counterparts. Clinicians
behavior of Clearfil SE Bond: (A) The presence of the molecule need to use extra caution with the solvent air-drying step of sim-
MDP to trigger chemical bonding to calcium in enamel and dentin plified adhesives, especially HEMA-free adhesives or adhesives
[26,27,84]. In fact, the same 13-year clinical study [75] found with very low HEMA content. These adhesives undergo phase-
that the enamel margins of restorations without previous enamel separation [90,91] forming droplets in the adhesive layer and the
etching had some minor issues with marginal integrity, but they transition between the adhesive layer and the hybrid layer (Fig. 13),
were still retained, most likely as a result of the chemical bond- which require a strong air-drying procedure to remove water and
ing from MDP; (B) The slight etching potential of MDP to provide facilitate the polymerization of the adhesive monomers. On the
other hand, HEMA-rich adhesives are prone to water sorption

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Fig. 12. (a) SEM micrograph of human enamel conditioned with the 1-step SE adhesive Prompt L-Pop (3M ESPE). The adhesive was not light cured. It was dissolved in acetone
for 12 h in a rotator. Note that the etching pattern resembles that of phosphoric acid as a result of the low pH of this adhesive (pH ≈ 1). Original magnification = 5,000X. (b)
TEM micrograph the adhesive-dentin interface formed by the ‘strong’ 1-step SE adhesive Prompt L-Pop (3M). Int – intertubular dentin; T – tubule; Ad – adhesive; H – hybrid
layer; R – Sp-adhesive mixed with residual smear plug; C – composite resin. Original magnification = 20,000X.

Fig. 13. (a) SEM micrograph of a replica of human enamel conditioned with G-Bond Plus (GC). The adhesive was dissolved in acetone for 12 h in a rotator. The replica of
droplets is depicted throughout the surface. Original magnification = 10,000X. (b) SEM micrograph of the adhesive-dentin interface formed with G-Bond Plus (GC) in self-etch
mode. This particular area corresponds to the top of the hybrid layer below the adhesive layer. The asterisks depict residual droplets. Original magnification = 10,000X. (c)
TEM micrograph of the adhesive-dentin interface formed with the G-Bond Plus (GC) in self-etch mode. H – hybrid layer; Int – intertubular dentin; Arrows – residual droplets
The dotted lines mark the hybrid layer thickness; Ovals – hydroxyapatite crystallites visible inside the hybrid layer denoting mild decalcification; Asterisks – residual smear
layer.

from the substrate via osmosis, forming droplets at the adhesive- clinical procedures, including direct composite restorations, indi-
composite interface, especially when the light polymerization of rect restorations, zirconia primers and silane coupling agent for
the composite resin is delayed or when a chemically-cured com- glass-matrix ceramics, as some universal adhesives also contain a
posite resin is used over the adhesive [92,93]. silane in their composition. They may be used with the ER or SE
strategy as relevant for the individual clinical situation. The advan-
tages and disadvantages of universal adhesives ae summarized in
5.4. Universal adhesives Table 6.
In the past, dentists have used dentin adhesives following
A new family of dental adhesives was launched in 2011. This new one specific adhesion strategy, ER or SE. However, clinicians now
generation of 1-bottle dental adhesives is known as universal adhe- demand more versatile materials. As a result, manufacturers have
sives (Table 2). They have become extremely popular in Restorative developed dental adhesives that are more user-friendly while
Dentistry [94]. Universal adhesives are indicated for a variety of

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Table 6
Advantages and disadvantages of universal adhesives.

Advantages Disadvantages

Extremely versatile, as they are recommended as ER and SE adhesives in Since etching dentin is not recommended with universal adhesives, a separate enamel
addition to selective enamel etching. acid-etching step is necessary, which increases the clinical application time.
Potential for chemical bonding to hydroxyapatite when used in SE mode. Clinical studies have reported that the SE strategy results in poor retention rate
compared to ER and selective enamel etching.
Seal dentin margins against nanoleakage when used in SE mode. Most universal adhesives require mixing with the respective dual-cure activator when
used with self- or dual-cure composite materials, such as build-up materials and resin
cements with aromatic tertiary amines in the initiator system.
Application of the adhesive in SE mode with a scrubbing movement They do not seal dentin margins well when dentin is etched with phosphoric acid.
increases enamel bond strengths.
No need to leave dentin moist when used in ER mode. Similar to classical 1-step SE adhesives, universal adhesives may behave as permeable
membranes after polymerization, allowing the permeation of fluids through the
adhesive layer to the surface and subsequent degradation of the resin-dentin interface
by hydrolysis.
Indicated for a wider variety of restorative procedures. Solvent evaporation time is a critical issue and must be extended, as water in their
composition may become entrapped if not properly evaporated, which results in
nanoleakage.
Indicated as zirconia primers. The incorporation of a silane in the adhesive solution does not improve bond strengths
to glass-matrix ceramics. A separate silane solution must be used.
Solvent evaporation time must be extended to remove the residual water that is in the
composition of the adhesive [71].

providing dentists with the possibility of selecting the adhesion tive and durable. It is still unclear whether the presence of MDP
strategy. With the advent of these universal adhesives, dentists in current universal adhesives improves their long-term clinical
can use the same adhesive tailored to a specific clinical situation behavior.
by selecting one of the adhesion strategies recommended by the Calcium is depleted from the dentin surface when dentin is
respective manufacturers. Besides the ER and SE strategies, uni- etched with phosphoric acid. Without calcium it is unclear how
versal adhesives may be applied as SE adhesives on dentin and ER MDP-containing adhesives are able to bond ionically to etched
adhesives on enamel, i.e. the selective enamel etching technique dentin through nanolayering. The lack of calcium may be respon-
previously mentioned. sible for the lower bond strengths and increase in nanoleakage
A few years after Fusayama’s total-etch technique in 1979 observed when Scotchbond Universal Adhesive (3 M) was applied
(simultaneous etching of enamel and dentin with phosphoric acid), as an ER adhesive in comparison with the SE strategy up to 1-year
Kuraray introduced a new self-cured dental adhesive in 1984 water storage [103–105]. Therefore, MDP-containing SE adhesives
specifically indicated for the total-etch technique. This adhesive, may need to be applied only on unetched dentin, while ER adhesives
Clearfil New Bond, included HEMA and, for the first time, included are more effective on enamel. The only option is to use the selec-
the molecule MDP [34,95,96]. The MDP monomer has been used in tive enamel etching technique, in which only enamel is etched with
the composition of the 2-step SE adhesive Clearfil SE Bond (Kuraray phosphoric acid [106]. In fact, etching enamel may not only enable
Noritake) since the late 1990s, when it was launched in Japan as the characteristic micromechanical interlocking into the enamel
Mega Bond (Kuraray). MDP includes a methacrylate polymerizable microporosities, but also potentiates the chemical bonding of MDP
end, a long hydrophobic 10-carbon chain, and a short hydrophilic around the enamel crystallites in etched enamel resulting in higher
phosphate component. It is currently widely used in dental adhe- bond strengths than other adhesives without MDP [107].
sives. In 2006, it was reported that calcium ions were leached from Universal adhesives do not include the hydrophobic bonding
hydroxyapatite to form an MDP-calcium salt layered structure on resin as the last step of the adhesive procedure, which may ren-
the hydroxyapatite surface [97]. der these adhesives more prone to interfacial degradation than
The addition of acidic functional monomers to universal adhe- 2-step SE adhesives such as Clearfil SE Bond. With this in mind, the
sives, such as MDP, distinguishes them from the classical 1-step addition of a non-solvated hydrophobic resin to universal adhe-
SE adhesives. The molecule MDP has been shown to interact with sives has been tested in vitro with favorable results up to 6 months
hydroxyapatite through a dual adhesion mechanism: (1) stable of aging in water [47,108,109]. However, this improvement does
ionic bonding to calcium is formed through a nanolayered struc- not seem to extrapolate to clinical behavior. A recent randomized
ture of MDP-Ca salts at the interface with hydroxyapatite [98–100]. clinical trial [110] resulted in lower retention rates in NCCLs when
Such hydrophobic nanolayering is deemed to improve the long- the hydrophobic bond resin was used with Scotchbond Universal
term durability of dentin and enamel bonding [93]; and (2) greater Adhesive (3 M). This clinical outcome was unexpected, as the addi-
enamel etching potential for MDP compared to other acidic func- tion of a hydrophobic bonding resin to classical 1-step SE adhesives
tional monomers [84]. improved their clinical behavior in a clinical study at two years [88].
In spite of the excellent adhesion capability of MDP as a func- When universal adhesives are applied as 1-step SE adhesives
tional monomer, it has been known for some time that adhesive they result in significantly lower enamel bond strengths than when
monomers with pH between 1.5 and 2.5, such as HEMA and MDP, used as 2-step ER adhesives [111,112]. In case dentists prefer to use
are susceptible to hydrolytic degradation [82]. This may be the these adhesives in the SE mode on enamel, it has been shown that
reason why the presence of HEMA and MDP in the same solution scrubbing the adhesive solution improves enamel bond strengths
inhibits nanolayering at the adhesive interface of a commercial uni- for specific universal adhesives [113]. This may be particularly rel-
versal adhesive [101]. In addition, many universal adhesives that evant for pediatric dentists to shorten the clinical procedure in
contain MDP do not seem to result in significant nanolayering [102]. children. However, etching enamel with phosphoric acid results in
It is the author’s view that, while the potential for MDP to bond significantly improved outcomes of universal adhesives even when
chemically to dentin via nanolayering exists in universal adhesives, the bonds are challenged with artificial aging [111,114]. Clinically,
there must be an ideal combination of adhesive components, pH, the use of phosphoric acid etching on enamel has also improved
and concentration of MDP, to make this adhesion mechanism effec- the performance of universal adhesives [65].

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Fig. 14. (a) SEM micrograph (backscattered mode) of the adhesive-dentin interface formed between the universal adhesive Single Bond Universal (3M) and dentin. This
specimen was part of a nanoleakage study using ammoniacal silver nitrate as the tracer. Note the deposition of silver ions as water-trees in the adhesive layer denoting
residual water. AD – adhesive; D – Dentin. Original magnification = 2,500X. (b) SEM micrograph in backscattered mode of the adhesive-dentin interface formed between the
universal adhesive Prime & Bond Elect (Dentsply) and dentin. This specimen was part of a nanoleakage study using ammoniacal silver nitrate as the tracer. Note the intense
deposition of silver ions in the hybrid layer and into the wall of the dentin tubules. This universal adhesive has acetone as the organic solvent. Acetone-based adhesives
usually need more applications than the number recommended by the respective manufacturer. This may explain the absence of an adhesive layer at the entrance of the
tubules, allowing the penetration of the composite resin (C) into the tubules. C – composite resin; H – hybrid layer; D – dentin. Original magnification = 5,000X.

Fig. 15. (a) SEM micrograph of the adhesive-dentin interface formed between a universal adhesive applied in etch-and-rinse mode and dentin. Dentin was partially dissolved
with 6N HCl for 30 sec and deproteinized with 5%NaOCl for 5 min. Note that the typical reticulation from the presence of collagen in the hybrid layer is only observed in
a <1 ␮m deep area (H). The characteristic reticular pattern on the hybrid layer is absent (asterisks) below this area. The collagen is dissolved by the deproteinizing agent
NaOCl when the collagen fibers are not fully enveloped by the resin from the adhesive. This phenomenon is known as hybridoid layer and ghost hybrid layer [62,104,174]. C
– composite resin; Rt – resin tag. Original magnification = 10,000X. (b) SEM micrograph in backscattered mode of the adhesive-dentin interface formed between a universal
adhesive applied in etch-and-rinse mode and dentin. Dentin was partially dissolved with 6N HCL for 30 sec and deproteinized with 5%NaOCl for 5 min. Note that reticulation
from the presence of collagen in the hybrid layer is only observed in a 1 ␮m deep area (H). Below this area, the characteristic reticular pattern on the hybrid layer is absent
(asterisks), for the same reason explained in Fig. 15a. C – composite resin; Rt – resin tag. Original magnification = 10,000X.

The 5-year data of the first clinical trial of a universal adhesive have incorporated silane into their universal adhesive [94,106] and
in 200 restorations in NCCLs has recently been released. This spe- do not recommend the application of a separate silane solution.
cific adhesive, Scotchbond Universal Adhesive, resulted in excellent However, the efficacy of the combined adhesive/silane solution for
retention rate when the adhesive was used in ER mode, regardless luting glass-matrix ceramic restorations is questionable [116], as
of the degree of dentin moisture (moist or dry). However, when the silane may not be stable in the adhesive solution [117,118].
used in the SE mode, it resulted in statistically lower retention rate The low pH of universal adhesives decreases the effectiveness of
and worse marginal staining [115]. the incorporated silane [118]. For this reason, the application of a
Dentists must keep in mind that universal adhesives are origi- separate silane solution is still recommended.
nally 1-step SE adhesives. Therefore, they contain up to 20% water
to enable the respective monomers to ionize as described above 5.5. Self-adhesive (SA) materials
for classical SE adhesives. Hence, the issue of leaving residual water
inside the adhesive-dentin interface also applies to universal adhe- A. Glass-ionomer cements (GICs):
sives, as observed with nanoleakage studies (Fig. 14). The solvent A summary of the advantages and disadvantages is laid out in
evaporation time is therefore a crucial issue for universal adhe- Table 7. GICs have been used as SA materials for over 50 years.
sives [55,71] as most manufacturers only recommend 5 sec. For They result from an acid-base reaction between aluminosili-
this reason, we currently teach extending the evaporation time cate glass and a polyalkenoic acid, commonly polyacrylic acid.
to 15 sec using gentle air drying from a dental air syringe. Our Although GICs have been described in the literature as the only
analyses with FESEM show that several universal adhesives do not restorative material able to truly self-adhere to tooth structure,
infiltrate etched dentin completely when used as per manufactur- they ‘borrowed’ the self-adhesive property from zinc polycar-
ers’ directions. They leave behind collagen fibers not enveloped by boxylate cement, which also has self-adhesive properties. These
the polymerized adhesive, which are easily dissolved in in vitro two materials share the same liquid, polyacrylic acid, one of sev-
experiments using sodium hypochlorite, a deproteinizing agent, to eral polyalkenoic acids used in current GICs. In fact, the first
challenge the dentin-adhesive interfaces (Fig. 15). commercial GIC had the term ‘polyacrylate’ in its name ASPA
Regarding the use of universal adhesives as part of the luting or alumino-silicate polyacrylate (Amalgamated Dental Company
procedure for glass-matrix restorations, four dental manufacturers DeTrey Division).

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Table 7
Self-adhesive materials (Type II GIC-based materials).

Advantages Disadvantages

Stable chemical bonding to calcium in the tooth structure without any Clinical studies have shown that the surface becomes rough rapidly.
intermediary adhesive.
Excellent sealing of dentinal margins, ideal restorative materials for root caries RMGICs contain small monomers, such as HEMA, therefore there is potential
lesions. for release of uncured monomers.
Fluoride release, potential for recharging. Surface degradation with moisture prior to full setting especially for classical
GICs.
No monomer release, no shrinkage (for classical GICs). The relevant initial fluoride release only lasts a few weeks.
Coefficient of thermal expansion identical to that of dentin; can be used as Water expansion of RMGICs may be an issue, especially in encased
dentin replacement in deep and wide preparations. environments such as the root canal.
Increase resistance to fatigue and reduce the deleterious effects of composite Not as esthetic nor mechanically strong as composite resins.
polymerization stress (cusp flexural and resulting enamel cracks) when used
underneath deep and wide posterior composite restorations [119].
Restorative GICs are able to increase the F release in acidic, cariogenic pH, More porous than composite resins, susceptible to surface staining.
when F is most needed to inhibit caries lesions.
Restorative GICs are a great resource for Pediatric Dentists, especially the More difficult to use clinically than composite resins.
reinforced type.

The in vitro and clinical outcomes of self-adhesive compos-

ite resins as direct restoratives and as pit-and-fissure-sealants
are not very favorable [126–129] and therefore their use is not
encouraged. A pit-and-fissure sealant, Vertise Flow, resulted in
62.9% retention rate at 2 years versus 95.7% for a traditional flow-
able composite applied with a separate dental adhesive [128].
As a restorative material in NCCLs, Fusio Liquid Dentin resulted
in a retention rate of only 33% at 6 months with 27 out of 40
restorations lost [129].
2) “Bioactive” restorative materials:
These materials have become very popular in recent years.
The commercial name that stands out is ACTIVA BioACTIVE-
RESTORATIVE (Pulpdent) [130]. According to the manufacturer
in 2013 [131], this material has properties such as “moisture
friendly, triple cure, fluoride releasing and radiopaque, no Bisphe-
nol A, no Bis-GMA, no BPA derivatives”. In addition, “strong,
Fig. 16. TEM micrograph of the adhesive-dentin interface formed by Fuji II LC (GC) durable, ionic restorative resins that release and recharge more
with dentin. G – glass particle; M – matrix; IZ – interaction zone; D – dentin. Original
magnification = 40,000X.
calcium, phosphate and fluoride than glass ionomers and tradi-
tional RMGIs, and have the physical properties and esthetics of
composites. They stimulate mineral apatite formation that seals the
material/tooth interface against microleakage, and they are the first
Research on GICs has confirmed that the bonding mechanism
dental restoratives with a bioactive resin matrix, shock-absorbing
involves carboxylic groups of the GIC that replace phosphate
resin component, and reactive ionomer glass fillers designed to
ions of the substrate and establish ionic bonds with calcium ions
mimic the physical and chemical properties of natural teeth”. In
of hydroxyapatite [120], slowly forming an ion-exchange layer
2015 [132], the properties claimed by the manufacturer were
between the tooth and the cement [121,122]. It is simultaneously
almost identical except that ‘triple-cure’ changed to ‘dual-cure’
an ionic bonding mechanism and a self-etching interdiffusion
and the materials ‘have a greater potential to recharge these min-
nanomechanical interaction, also known as surface interaction
erals than glass ionomers and traditional RMGls’.
zone or surface intermediate layer [123] (Fig. 16).
The reason the present author decided to include GICs in this
review is that they are often overlooked as adhesive materials.
One important change from 2013 to 2015 was in the instruc-
Yet, systematic reviews have produced enough evidence for type
tions for use. Whereas in the 2013 instructions [131], a bonding
II GICs to be considered as the best dentin adhesive/restorative
agent was only recommended in non-retentive restorations such
material in non-carious cervical lesions [49,85,124]. Resin-
as class V lesions, the 2015 instructions [132] specifically stated
modified GICs have also been used as a separate adhesive layer
‘apply a bonding agent of your choice’. This change may actually
underneath composite resin restorations. Fuji Bond LC is a liner
be a very relevant change and may lead to improved clinical out-
version of the restorative resin-modified GIC (RMGIC), Fuji II LC
comes. When this restorative material was inserted in class I and
(GC) [89]. The retention rate of Fuji Bond LC at 3 years was found
class II preparations without a separate adhesive, the failure rate at
to be 94% when used in conjunction with Silux Plus (3 M), and
1 year was 24.1% [133]. The authors stated that the study had to be
100% with Estio LC (GC) [125] in NCCLs, which is certainly a better
discontinued due to the high failure rate.
outcome than with many resin-based dental adhesives.
Regarding the composition [134], this restorative material con-
B. Resin-based self-adhesive (SA) materials:
tains a blend of diurethane and other methacrylates with modified
polyacrylic acid (44.6%), amorphous silica (6.7%), and sodium flu-
1) Flowable composite resins with (claimed) self-adhesion to tooth oride (0.75%) according to the relevant SDS information. However,
structure, including Constic (DMG), Fusio Liquid Dentin (Pen- the SDS information only includes components that are hazards.
tron/Kerr), Vertise Flow (Kerr), and Surefil One (Dentsply). The The terminology used to characterize these materials, i.e., ‘bioac-
respective compositions are available online in the respective tive’ and ‘biomineralization’, has been questioned recently in a
manufacturer’s Safety Sata Sheets (SDS) documents.: paper in which the authors suggested to limit these terms only

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5.7. What does the future hold for dental adhesives?

There have been several different new molecules and techniques

within the last 10-15 years intended to improve dentin adhesion,
but most were solely doable in the laboratory and not applicable to
clinical dentistry. Others, such as new analogues of MDP (different
carbon chain size, maintaining the methacrylate and the phosphate
groups), were tested 6-7 years ago without further known devel-
opments.
Adhesives with antibacterial properties by incorporation of an
antibacterial agent were first described over 25 years ago, but
problems may result from the leaching of the inhibitory agent
to the oral environment and to the pulp, in addition to degra-
dation of the physical properties of the composite resin or the
adhesive. The synthesis of the antibacterial quaternary ammo-
nium methacrylate MDPB (12 methacryloyloxydodecylpyridinium
bromide) resulted in the first successful antibacterial composite
Fig. 17. TEM micrograph of Fuji II LC (GC) after setting. G – glass particle; M – matrix;
Asterisk – silica gel around the glass particles. Original magnification = 100,000X. resin [151] and dentin primer [152]. This antibacterial monomer
combines a quaternary ammonium compound, dodecylpyridinium
bromide, with a methacryloyl group. MDPB covalently bonds to the
resin matrix becoming immobilized to provide long-term contact-
to scientifically proven dental materials that release substantial inhibition against oral bacteria. It possesses potent antibacterial
quantities of ions for specific biomineralization in the clinical activity against several bacteria, including S. mutans, and is able
environment [135]. In a review article published in 2015 in Pedi- to eliminate bacterial inside dentinal tubules of tooth prepara-
atric Dentistry [136], the authors questioned if these materials are tions. Furthermore, the cured resin does not undergo decline in
resin-based composites with RMGI properties or a RMGI that has mechanical properties, retaining its inhibitory effects against bacte-
resin-based composite physical strengths. In fact, a similar material rial growth. MDPB is incorporated in a commercial dental adhesive,
has been approved by the FDA as a RMGIC [137]. Clearfil SE Protect (Kuraray Noritake), formerly Clearfil Protect
The same issue, i.e., whether a material is a true GIC or a com- Bond. In fact, this 2-step SE adhesive is basically Clearfil SE Bond
posite resin, is not new. The comparative analysis of the relevant with MDPB and fluoride added to its composition.
physical properties, the absence of an acid-base reaction and silica Other recent experimental adhesives with antibacterial prop-
gel layer around the glass particles characteristic of true GIC mate- erties have been tested, including adhesives with another quater-
rials (Fig. 17), as well as the fact that some of these supposedly nary ammonium monomer, dimethylaminododecyl methacrylate
GIC-based materials do not set in the dark, have been reported by (DMADDM), which has been recently used in several research
several authors. It is still unclear if the nomenclature used for some projects with encouraging results [153,154].
materials marketed as GICs and RMGICs is accurate [18,138–142]. Chlorhexidine has been used as an antibacterial agent in Peri-
odontology for over 30 years [48]. More recently it has been added
to phosphoric acid etchants, experimental primers and, at least, one
5.6. Dentin matrix metalloproteinase-inhibitors commercial dental adhesive [48]. There are a few chlorhexidine-
containing scrubbing solutions to be applied prior to the dentin
Dentin collagen fibrils contain inactive forms of proteolytic adhesive. However, it is not clear if there is a clinical advantage by
enzymes called matrix metalloproteinases (MMPs) [48]. These using chlorhexidine during the adhesive procedure.
enzymes, which are found in odontoblasts and mineralized or dem- Silver nanoparticles have also been used in several studies with
ineralized human dentin, may play a role on the degrADAtion of promising results regarding toxicity and preservation of the bonds
resin-dentin bonds in vitro [143,144] and in situ [145,146]. [155,156]. Dentin adhesives and resin cements containing nano-
Dentin MMPs are activated by SE or by ER adhesives during tubes loaded with different active substances have also been used
adhesive procedures in vitro [48,145]. MMPs may degrade the colla- in vitro within the last 10 years with very encouraging outcomes
gen within deficiently resin-infiltrated hybrid layers, reducing the [157–160].
longevity of adhesive restorations in vitro [147]. Another avenue of research includes antimicrobial peptides
The use of exogenous MMP inhibitors, such as chlorhexidine, incorporated in dental adhesives [161–163]. A peptide derived from
has been advocated to help improve the longevity of adhesive a salivary protein [164] with amphipathic and antimicrobial prop-
restorations [48]. Despite the publication of over 200 in vitro and erties has the potential to achieve hydrophobicity and antibiofilm
in situ studies within the last 15 years demonstrating the benefits properties underneath adhesive restorations [161,165]. The ability
of applying potential MMP inhibitors as an adjunct to dentin bond- to form hydrophobic coatings on dentin with intrinsic antibacte-
ing, only a few clinical studies with follow-up over 2 years have rial properties would forever change the way we currently struggle
been published [148,149]. These clinical studies have not reported with the clinical challenges related to dentin adhesion.
any benefit from using chlorhexidine as an MMP inhibitor, which
contradicts the findings of most in vitro and in situ studies. In fact,
a meta-analysis concluded that there is insufficient evidence to 6. Conclusions
recommend or refute the degrADAtion inhibitory effect of MMP
inhibitors used for cavity pretreatment prior to inserting adhesive 1) Dentin in NCCLs is still the most challenging and unpredictable
restorations [150]. The conclusion of this review’s author is that coronal substrate for adhesion.
the relevance of the use of MMP inhibitors with dentin adhesives is 2) In vitro results cannot be directly extrapolated to clinical prac-
merely academic, as no clinical validation has been found after all tice.
these years. In fact, it is basically an extra step added to the clinical 3) Leaving dentin moist after rinsing the etchant may leave too
procedure without clear clinical benefit. much water inside the dentin surface. Scrubbing the primer

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