Received: 2 May 2022 Accepted: 1 June 2022

DOI: 10.1002/cap.10211

C A S E S T U DY

PDGF-BB-enriched collagen matrix to treat multiple gingival

recessions with the tunneled coronally advanced flap
Shayan Barootchi1,2,3 William V. Giannobile4 Lorenzo Tavelli2,3,4

1
Department of Periodontics and Oral Medicine,
University of Michigan School of Dentistry, Ann Abstract
Arbor, Michigan, USA Background: With technological advancements in reconstructive periodontol-
2
Center for clinical Research and evidence ogy, traditional protocols for the treatment of gingival recessions (GRs) can be
synthesis In oral TissuE RegeneratION challenged. This manuscript presents preliminary findings of a novel minimally-
(CRITERION), Ann Arbor, Michigan, USA
invasive approach for the regenerative treatment of multiple adjacent GR defects.
3
Center for clinical Research and evidence Methods: Two healthy adults were treated as part of this study. Multiple adja-
synthesis In oral TissuE RegeneratION
(CRITERION), Boston, Massachusetts, USA cent GRs in both subjects (1 in the mandible, and 1 in the maxilla) were treated
4
Department of Oral Medicine, Infection, and
employing a tunneled coronally advanced flap (TCAF) design, with the applica-
Immunity, Division of Periodontology, Harvard tion of a cross-linked collagen matrix (CCM) that was enriched with recombinant
School of Dental Medicine, Boston, human platelet-derived growth factor-BB (PDGF-BB) that was also applied on the
Massachusetts, USA
prepared root surfaces. Clinical, ultrasonographic, esthetic, and patient-reported
outcomes were observed at approximately 6- and 18-month time points.
Correspondence
Shayan Barootchi, Department of Periodontics Results: All sites healed uneventfully after the treatments. Complete root cover-
and Oral Medicine, University of Michigan School age was achieved and maintained throughout the follow-up observations, from
of Dentistry, Ann Arbor, MI, USA. 6 to 18 months. Patients reported minimal discomfort and reduction of dentinal
Email: [email protected]
hypersensitivity at the augmented sites. The areas augmented with CCM + PDGF-
BB revealed an increased soft tissue thickness relative to baseline (pretreatment)
measures, as well as reduction in the level of the facial bone dehiscences.
Conclusion: This article describes the success of two cases of a novel minimally
invasive regenerative approach for the treatment of multiple adjacent GR defects
by the TCAF, using a CCM loaded with PDGF-BB. This approach offers potential as
a minimally-invasive method to repair multiple adjacent GRs.

KEYWORDS
gingival recession, platelet-derived growth factor, periodontics, regenerative medicine, tissue
engineering, tissue scaffolds

INTRODUCTION a direction of minimal invasiveness and optimized patient-

centered outcomes,5 many have recognized the drawbacks
The occurrence of a gingival recession (GR) is a common that are inherent, particularly the requirement of palatal
finding in clinical practice.1 When it comes to treatment, harvesting.6,7 Namely, in a recent study, we found that some
the scientific literature is in agreement that irrespective of patients, even after a decade had surpassed the date of
the outcome of therapy—whether root coverage, or mod- their original treatment, still remembered the pain they
ification of the soft tissue phenotype—the traditionally experienced after a palatal harvesting procedure, which
applied autogenous connective tissue graft (CTG) still ranks also negatively impacted their decision to accept a similar
as the “gold standard” approach.2–4 Nonetheless, with rou- therapy in current day.6
tine implementation of this technique, and with realization Thus, clinicians now strive to adopt minimally invasive
of the path of contemporary periodontics to be moving in techniques for challenging the status quo and finding

This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium,
provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.
© 2022 The Authors. Clinical Advances in Periodontics published by Wiley Periodicals LLC on behalf of American Academy of Periodontology.

224 wileyonlinelibrary.com/journal/cap Clin Adv Periodontics. 2022;12:224–232.

 21630097, 2022, 4, Downloaded from https://aap.onlinelibrary.wiley.com/doi/10.1002/cap.10211 by CochraneArgentina, Wiley Online Library on [21/07/2024]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License
CLINICAL ADVANCES IN PERIODONTICS 225

alternatives to the use of the autogenous CTG.2,7,8 Among (pre-treatment), 6-month and 18-month follow-up. Gingival
them, has been more routine implementation of autoge- thickness (GT) and buccal bone dehiscence (BBD) were eval-
nous soft tissue graft substitutes to enhance their efficacy uated at the same time points using ultrasonography.16–18
using growth factors or bioactive agents, as well as employ- Briefly, this technology is commercially available as an
ment of less invasive and novel surgical designs.9 ultrasound imaging device (ZS3, Zonare/Mindray, Moun-
An example is the newer generation of a xenogeneic tain View, CA, USA) coupled with a 24 MHz (64 µm
collagen matrix, which has principally undergone chemi- axial image resolution) and miniature-sized (approximately
cal cross-linking to enhance its mechanical stability, which 30 mm long, x 18 mm wide x 12 mm thick) probe pro-
due to its porous structure, may also act as a viable car- totype (L30-8) to generate ultrasound images. The scans
rier for a biologic agent, and a scaffold for the ingrowth were taken at the midfacial aspect of each treated tooth
of cells, enabling a growth factor-mediated root coverage and were saved in the Digital Imaging and Communica-
procedure.10 In particular, an in vitro study reported an tions in Medicine (DICOM) format. A commercially available
increased cellular population and metabolic activity in this software (Horos, version 3.3.6, Horos Project) was utilized
matrix when utilized as a scaffold for one of the most com- for evaluating GT at reference points 1.5, and 3 mm from
monly utilized biologic agents, the recombinant human the gingival margin and for assessing the distance between
platelet-derived growth factor-BB (rhPDGF-BB).11 Thus, in the buccal bone and the cemento-enamel junction (CEJ)
the current manuscript, we describe a minimally invasive at the midfacial aspect of the treated sites (BBD).19 The
approach for the treatment of multiple adjacent GRs, by professional esthetic evaluation was performed using the
virtue of a biologic-mediated root coverage procedure with root coverage esthetic score (RES)20 at the 6- and 18-month
the application of the cross-linked collagen matrix (CCM) follow up.
incorporated with rhPDGF-BB. Patient-reported outcome measures (PROMs) were
assessed using a set of questionnaires with a visual ana-
logue scale (VAS) from 0 to 100 to assess treatment
MATERIALS AND METHODS satisfaction and esthetic outcomes at the final follow-up.

Design and objective of this feasibility study

Case 1: TCAF + CCM loaded with rhPDGF-BB
The present manuscript illustrates the combined applica- for multiple maxillary GRs
tion of CCM + rhPDGF-BB with the tunneled coronally
advanced flap (TCAF)12,13 for the treatment of multiple GRs A 42-year-old healthy female patient presented with
in two nonsmoking systemically and periodontally healthy esthetic concerns for generalized RT1 and RT2 GRs in
individuals. Both patients were recruited and treated at the the maxillary region. She also reported substantial dental
Department of Periodontics and Oral Medicine, School of hypersensitivity on the right canine, which was also associ-
Dentistry, University of Michigan between November 2019 ated with a noncarious cervical lesion (NCCL). The GRs were
and January 2020, and provided their informed consents. characterized by the presence of at least 1.5 mm of KTW
The study is in accordance with Declaration of Helsinki of (Figure 1A–C).
1975, as revised in Fortaleza in 2013 and the manuscript It was decided to perform a minimally invasive approach,
has been prepared according to the CARE guidelines for involving a combination of coronally advanced flap
improving research reporting in case reports.14 (CAF) and tunnel (TUN) technique (TCAF, as previously
To be considered, the selected patients must have had: described)12,13 with site-specific application of a CCM
(i) an esthetic concern or hypersensitivity associated with loaded with rhPDGF-BB for the maxillary right canine. The
GR, (ii) age ≥ 18 years, (iii) presence of RT1 or RT2 multi- rationale for this approach was to open the flap only at the
ple adjacent GRs,15 (iv) at least 1.5 mm of keratinized tissue right premolar and canine area to gain access for the inser-
width (KTW) around the included teeth. tion and stabilization of the CCM soaked with the growth
The following were considered as exclusion criteria: factor, aiming for root coverage and simultaneous gingival
(i) subjects with an uncontrolled systemic disease (e.g., dia- phenotype modification (Figure 1D). The presence of the
betes, etc.), (ii) smokers, (iii) presence of active periodontal NCCL was address by performing a bilaminar approach,
disease, (iv) previous surgical procedure at the site to be with the biomaterial positioned over the NCCL to prevent
treated, (v) individuals taking medications, which could the collapse of the flap.21,22
interfere with the healing of the soft tissues, and (vi) known The other areas were tunneled and coronally advanced
allergy to any of the biomaterials to be used. without receiving any graft materials, as previously
described by Rasperini and coworkers.23 The papillae
at the level of the right premolars and the canine were
Outcome measures incised using a miniblade (Salvin Dental Specialties, Char-
lotte, NC, USA), and a vertical incision was placed distal to
The clinical parameters of recession depth (REC), clinical the second right premolar. These areas were then raised
attachment level (CAL) and KTW were assessed at baseline split thickness interproximally and full thickness at the
 21630097, 2022, 4, Downloaded from https://aap.onlinelibrary.wiley.com/doi/10.1002/cap.10211 by CochraneArgentina, Wiley Online Library on [21/07/2024]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License
226 BAROOTCHI ET AL.

F I G U R E 1 Tunneled coronally advanced flap with a cross-linked collagen matrix loaded with recombinant human platelet-derived growth factor-BB
(tunneled coronally advanced flap [TCAF] + cross-linked collagen matrix [CCM] + rhPDGF-BB) for the treatment of multiple maxillary gingival recessions.
(A–C) Baseline. (D) Flap design involving the incision and opening of the papillae of the right premolars and canine only. The remaining areas were
tunneled. (E) Cross-link collagen matrix. (F) Collagen matrix saturated with rhPDGF-BB. (G) Chemical root planing with 24% EDTA for 2 min. (H–J)
Stabilization of the collagen matrix to the right premolars and canine. (K) The flap was coronally advanced and sutured approximately 2 mm coronally to
the cemento-enamel junction. Note that the left quadrant until the right lateral incisor was tunneled and coronally advanced without receiving any
grafts, given the overall thick gingival phenotype. (L) 2-week postop. (M–O) Outcomes at the 18-month follow-up

midfacial aspect of the premolars and canine until exposing and then saturated with rhPDGF-BB (GEM21, Lynch Bio-
2 mm of bone. logics, Franklin, TN, USA) using a micro-injection needle
The region distal to the right incisor and the left hemi- (Figure 1E,F). The CCM were then left in the dappen dish for
maxilla were tunneled using straight and angulated tun- 15 min24 The root surfaces were scaled, planed and chem-
neling miniblades (Butterfly, Cavenago di Brianza, Italy). ically conditioned using 24% of EDTA for 2 min. rhPDGF-BB
Careful attention was made to maintain the integrity of was also applied onto the dried root surfaces before stabi-
the papillae. After removal of muscular insertions from the lizing the CCM (Figure 1G). Simple interrupted sutures (6/0
flap, the papillae were detached from the bone using tun- and 7/0 PGA) (Butterfly, Cavenago di Brianza, Italy) engag-
neling miniblades (Butterfly, Cavenago di Brianza, Italy) ing the matrix and the de-epithelialized anatomical papillae
and a papilla elevator (American Dental Systems, Vaterstet- were performed to stabilize the CCM on the recipient bed,
ten, Germany). The incised anatomical papillae were de- approximately at the level of the cemento-enamel junc-
epithelialized with a miniblade (Salvin Dental Specialties, tion (CEJ) or 1 mm apical (Figure 1H–J). The TCAF was then
Charlotte, NC, USA). A CCM (Geistlich Fibro-Gide, Geistlich coronally advanced and stabilized approximately 2 mm
Pharma North America, Princeton, NJ, USA) was trimmed above the CEJ with sling sutures and simple interrupted
 21630097, 2022, 4, Downloaded from https://aap.onlinelibrary.wiley.com/doi/10.1002/cap.10211 by CochraneArgentina, Wiley Online Library on [21/07/2024]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License
CLINICAL ADVANCES IN PERIODONTICS 227

F I G U R E 2 Tunneled coronally advanced flap with a cross-linked collagen matrix loaded with recombinant human platelet-derived growth factor-BB
for the treatment of multiple mandibular gingival recessions. (A) Baseline. (B–C) Tunneled coronally advanced flap (TCAF) design, showing the different
flap preparation areas. (D) De-epithelialization of the anatomical papillae of the canine after flap elevation. Note that the access provided by the selective
flap preparation typical of the TCAF allowed for a better access at the level of the mental foramen region, facilitating flap releasing without damaging the
mental nerve. (E) Cross-link collagen matrix saturated with rhPDGF-BB. (F–G) Stabilization of the collagen matrix on the recipient site. Note that there are
two simple interrupted sutures stabilizing the matrix to the de-epithelialized papillae and an anchoring periosteal suture for further stabilize and
compress the graft. (H) Flap colure. (I) 18-month follow-up

sutures (6/0 and/or 7/0 polypropylene) (Ethicon, Johnson substitutes compared to autogenous CTG, it was decided
& Johnson, Somerville, NJ, USA) at the level of the papillae, to use a CCM soaked with rhPDGF-BB.
completely covering the graft. Simple interrupted sutures A TCAF with one vertical incision on the mesial aspect
were performed at the level of the vertical incision, (7/0 of the canine was performed.12,13 The papilla between the
polypropylene) (Ethicon, Johnson & Johnson, Somerville, canine and the first premolar was also incised, with an
NJ, USA) (Figure 1K). oblique incision anticipating the rotation of the flap when
coronally advanced (Figure 2B,C). Miniblades (Salvin Den-
tal Specialties, Charlotte, NC, USA) were used to elevate the
Case 2: TCAF + CCM loaded with rhPDGF-BB two papillae of the canine in a split-thickness manner, while
for multiple mandibular GRs the elevation of the midfacial portion of the flap at the level
of the canine proceeded full-thickness until exposing 2 mm
A 49-year-old periodontally and systemically healthy of labial bone. The other papillae, from the distal papilla
female presented with multiple GRs in the lower right of the first premolar to the distal papilla of the first molar
quadrant associated with esthetic concern and mild dental (dental implant), were preserved in integrity, and detached
hypersensitivity at the level of the canine (Figure 2A). The from the underlying bone using tunneling miniblades (But-
patient reported that she had been previously treated with terfly, Cavenago di Brianza, Italy) and a papilla elevator
a graft from the palate in other areas of the mouth and, (American Dental Systems, Vaterstetten, Germany). The flap
given the postoperative pain that she had experienced, she was tunneled until the distal aspect of the first molar,
asked whether it was possible to address her concern with in order to achieve adequate release and advancement
alternative techniques. After a discussion of advantages, of the flap (Figure 2C). The access provided by the inci-
disadvantages and expected outcomes of soft tissue graft sion of the papillae at the level of the canine allowed for
 21630097, 2022, 4, Downloaded from https://aap.onlinelibrary.wiley.com/doi/10.1002/cap.10211 by CochraneArgentina, Wiley Online Library on [21/07/2024]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License
228 BAROOTCHI ET AL.

inserting a miniblade (Salvin Dental Specialties, Char- a buccal bone level gain of 2.107 mm from baseline to 18
lotte, NC, USA) and releasing the muscular insertion, as months.
well as identifying and protecting the mental nerve. The In the case 2, complete root coverage was obtained at
incised anatomical papillae were de-epithelialized using a the canine and first premolar after 18 months, while the sec-
miniblade and the root surfaces were chemically (24% of ond premolar showed a residual recession of 1 mm, which
EDTA for 2 min) and mechanically treated (Figure 2D). A was anticipated due to the interproximal attachment loss
CCM (Geistlich Fibro-Gide, Geistlich Pharma North Amer- on the distal aspect of the tooth. The patient rated her treat-
ica, Princeton, NJ, USA) was trimmed and saturated with ment satisfaction and esthetic assessment 100 and 92.97.
rhPDGF-BB (GEM21, Lynch Biologics, Franklin, TN, USA) as The professional esthetic score was 7.67 ± 2.31. In terms of
described above (Figure 2E). The CCM was inserted into the ultrasonographic outcomes, a GT gain (from baseline to 18
flap from the canine area until reaching the second pre- months) of 0.458 mm and 0.671 mm was found when the
molar. The CCM was then sutured to the de-epithelialized soft tissue thickness was measured 1.5 and 3 mm below the
anatomical papillae of the canine with two simple inter- gingival margin, respectively. The BBD at baseline was 4.492
rupted sutures and a suture anchoring to the periosteum mm (which was also confirmed intraoperatively), while at
apical to the graft (7/0 PGA) (Butterfly, Cavenago di Brianza, the last visit a BBD of 3.041 mm was noted on the ultrasound
Italy) (Figure 2F,G). The TCAF was then coronally advanced scan, indicating a reduction of BBD of 1.451 mm (Figure 4).
and stabilized approximately 2 mm above the CEJ with sling
and simple interrupted sutures at the level of the papil-
lae, and simple interrupted sutures for the vertical incision DISCUSSION
(6/0 and 7/0 polypropylene) (Ethicon, Johnson & Johnson,
Somerville, NJ, USA) (Figure 2H). With development of novel technologies, and the emer-
Both patients received similar oral and written postoper- gence of biomaterials and bioactive agents, the field of
ative instructions and were prescribed Ibuprofen (600 mg regenerative periodontal medicine is progressively moving
every 4–6 h for the first 3 days, followed by its prescription as in a direction of highlighting patient-centered outcomes
needed), Amoxicillin (500 mg 3 times a day for 7 days), and and increasing treatment efficiency by reducing intra-
a chlorhexidine mouth rinse (0.12% twice daily for 1 min for surgical time, postoperative morbidity, and complications.
14 days). The sutures were removed 2 weeks after the surgi- Conceivably, the impact of patients’ own perception of our
cal procedure, at which point the subjects were instructed treatments, including intra- and postoperative discomfort,
to resume mechanical tooth brushing at the operated area surgical chair time (also for clinicians) and the possibility of
using an extra-soft bristle toothbrush for approximately 4 adverse events, will likely soon determine even more of the
weeks, prior to switch to a soft bristle toothbrush. selection of our therapeutic approaches.
Appropriately, the concept of biologic factor-mediated
root coverage, and the application of CTG-substitutes have
RESULTS been more so highlighted recently. As a result, several
combination therapies involving biologic agents and CTG
The healing was uneventful and limited postoperative substitutes have been explored over the years to further
morbidity was reported by both patients. enhance the properties of dermal or collagen scaffolds and
In the case 1, complete root coverage was observed at matrices. Conceptually, the utilization of “enriched” and
the treated sites at 6 and 18 months (Figures 1 and 3). The “enhanced” graft substitutes in the treatment of GRs can be
patient reported reduced but mild residual dental hyper- a fundamental change in patient care, given the possibility
sensitivity when using the air-spray test at the 6-month to avoid a secondary surgical site for the CTG harvesting.
visit that however, disappeared at the 18-month follow- Nonetheless, the literature has yet to support this notion,
up. Patient’s reported treatment satisfaction and esthetic particularly as it relates to a generalized recommendation
assessment at the last visit were both 100. The professional as a substitute to the gold standard autogenous graft.
esthetic evaluation using the RES was 9.13 ± 0.64, respec- In these two cases, we present the step-by-step proto-
tively. Ultrasonographic assessment of tooth #6 revealed col of treating multiple adjacent GRs with a collagen matrix
that the GT at baseline was 0.756 and 0.692 mm, when that incorporated rhPDGF-BB, through a surgical design
measured 1.5-mm and 3-mm apical to the gingival margin that was specifically used for this application, namely the
respectively. The corresponding GT at 18 months was 1.541 TCAF.12,13 Indeed, most of the stated advantages of the
and 1.306 mm, indicating that the increase in GT 1.5 mm TCAF (stabilization of the matrix, avoiding vertical incisions,
below the gingival margin was 0.785 mm, and the GT gain etc.) are inherent with the CAF or TUN, which tradition-
3 mm apical to the gingival margin was 0.614 mm. The BBD ally have been denoted distinct from one another.25,26 The
at baseline was 5.982 mm, as also confirmed intraopera- proposed TCAF combines the advantages of the individual
tively using a periodontal probe. A BBD of 3.411 mm and techniques of CAF and TUN, according to site-specific crite-
3.875 mm was observed on the ultrasonographic scans at ria and indications, such as reducing the number of vertical
the 6- and 18-month follow-up a, respectively, indicating releasing incisions when possible (e.g., in the esthetic zone
 21630097, 2022, 4, Downloaded from https://aap.onlinelibrary.wiley.com/doi/10.1002/cap.10211 by CochraneArgentina, Wiley Online Library on [21/07/2024]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License
CLINICAL ADVANCES IN PERIODONTICS 229

F I G U R E 3 Clinical and ultrasonographic outcomes of case 1. (A) Baseline. (B) Ultrasonographic scan of the midfacial aspect of tooth #6, where the
clinical crown (“Cr”), the root (“R”), the crestal bone “CB,” the cemento-enamel junction (“CEJ”) and the soft tissue (“St”) are pointed out. Note that the CEJ,
CB, and the soft tissue are highlighted in the second scan. (C) Clinical presentation of the canine at baseline. (D) 6-month outcomes. (E) Ultrasonographic
scan of the midfacial aspect of tooth #6 at 6 months. Note the reduction of buccal bone dehiscence (distance between CEJ and CB) compared to the
baseline. (F) Clinical presentation of the canine at 6 months. (G) 18-month outcomes. (H) Ultrasonographic scan of the midfacial aspect of tooth #6 at 18
months. Note the reduction of buccal bone dehiscence (distance between CEJ and CB) compared to the baseline. (I) Clinical presentation of the canine at
18 months

or a posterior region), increasing visibility for a particular treated with the original soft tissues inherent. This con-
site and enhanced ability for graft stabilization (particularly cept of selective and site-specific gingival phenotype
important as it relates to a biologic factor-soaked matrix), modification has been recently suggested in the
as well as maintenance of the integrity of weaker papillae literature,23,27 and in line with these recommendations,
such as those with interproximal attachment loss (result- we based our approach on presurgical clinical and ultra-
ing in a more favorable environment for early nutrition and sonographic evaluation of periodontal structures of the
integration of the graft).12,13 teeth to be treated, in terms of KTW and GT. In addition, in
Indeed, the scope of minimal invasiveness in root light of the present findings of our pilot report, BBD could
coverage procedures does not only include avoiding be another factor to consider in the scope of site-specific
palatal harvesting and vertical releasing incisions. It also treatment recommendations, relative to the use of grafting
encompasses the concept of site-specificity in rendering materials and biologic agents. Indeed, an interesting find-
treatments,5 which can translate into the avoidance of ing from our pilot analysis, was the decrease in the level of
any additional biomaterials or grafts when applicable, the BBD that we noticed as a result of the treatments, at
through assessment of the local soft tissue phenotype. follow-up time points.
As we illustrated in this report, some of the treated sites It is well known that rhPDGF-BB is a potent mitogen
did not receive any graft or biomaterials and were merely for fibroblasts and periodontal ligament cells.28,29 When
 21630097, 2022, 4, Downloaded from https://aap.onlinelibrary.wiley.com/doi/10.1002/cap.10211 by CochraneArgentina, Wiley Online Library on [21/07/2024]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License
230 BAROOTCHI ET AL.

F I G U R E 4 Clinical and ultrasonographic outcomes of case 2. (A) Baseline. (B) Ultrasonographic scan of the midfacial aspect of tooth #27, where the
crestal bone “CB,” the cemento-enamel junction (“CEJ”) and the soft tissue (“St”) are pointed out. (C) 18 months. (D) Note that the distance between the
CEJ and the CB appeared to be reduced from baseline to 18 months

combined with beta-tricalcium phosphate for the treat- been suggested that a greater increase in soft tissue thick-
ment of isolated GRs in humans, rhPDGF-BB was found ness may be expected following soft tissue grafting at sites
to promote regeneration of Sharpey’s fibers, new cemen- with NCCLs compared to sites without these defects, due
tum, and new bone.30 The regenerative outcomes of to the fact that the graft material is positioned on an unre-
rhPDGF-BB have also been showed clinically via re-entry stored concavity that may further enhance its properties
procedures.30,31 In our assessment of the two treated cases of space maintenance resulting in an increased soft tissue
in this report, we observed a reduction of BBD of approx- thickness gain.40
imately 2 mm in an upper canine and 1.5 mm in a lower It is important to bear in mind the limitations of this
canine that received the CCM with rhPDGF-BB. Although report. Indeed, the demonstration of two successfully
the ultrasonographic nature of this finding does not allow treated cases does not stand alone as “evidence”for a gener-
for drawing conclusions in regard to periodontal regen- alized treatment recommendation or guideline, and neither
eration, speculations can be made from this view. Firstly, was this the intent of this report. Adequately-designed and
readers should be aware that several studies have demon- sufficiently powered randomized clinical trials, preferably
strated ultrasonography to be a reliable and reproducible with extended follow-up times are needed to validate our
method for assessing oral and periodontal tissues,32,33 with findings, as it pertains to the growth factor (rhPDGF-BB), the
comparable outcomes to cone-beam computed tomogra- scaffolding matrix (CCM), and the benefits of the proposed
phy, in particular for assessment of BBD.33–35 In line with a TCAF approach. The intention of this paper is to describe the
recent animal study showing that this novel CCM alone can feasibility of a minimally invasive approach when attempt-
promote periodontal regeneration when used in infrabony ing root coverage and inspire future application of such
defects,36 it can be assumed that the CCM could serve as combination therapies with different growth factors and
an appropriate carrier for the sustained and progressive bioactive agents, in the common aim of enhancing patient-
release of rhPDGF-BB, resulting in BBD reduction and possi- oriented outcomes. The concept of growth factor-mediated
ble periodontal regeneration. The sponge-like composition root coverage to substitute standard treatments, while cer-
of the CCM which carried the rhPDGF-BB may have also tainly appealing, requires further validation through solid
contributed to the chemotaxis of cells from the periodon- scientific evidence. In particular, noninferiority studies with
tal ligament and alveolar bone,36,37 that are characterized adequate designs are required for challenging this sta-
by the presence of receptors for PDGF on their surface.38,39 tus quo. Nonetheless, as we embark upon a new era in
Ultrasonography also revealed a substantial gingival contemporary periodontal treatments and individualized
thickness gain at sites grafted with CCM + rhPDGF-BB. It has approaches for our patients, such therapies, if validated
 21630097, 2022, 4, Downloaded from https://aap.onlinelibrary.wiley.com/doi/10.1002/cap.10211 by CochraneArgentina, Wiley Online Library on [21/07/2024]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License
CLINICAL ADVANCES IN PERIODONTICS 231

and generalized can lead to a paradigm shift in our daily 9. Stefanini M, Mounssif I, Barootchi S, Tavelli L, Wang HL, Zucchelli G.
practice. An exploratory clinical study evaluating safety and performance of a
volume-stable collagen matrix with coronally advanced flap for single
gingival recession treatment. Clin Oral Investig. 2020;24:3181-3191.
10. Asparuhova MB, Stahli A, Guldener K, Sculean A. A novel volume-
CONCLUSIONS stable collagen matrix induces changes in the behavior of primary
human oral fibroblasts, periodontal ligament, and endothelial cells.
The present report describes a novel minimally invasive Int J Mol Sci. 2021;22:4051.
11. Agis H, Collins A, Taut AD, et al. Cell population kinetics of collagen
reconstructive approach for the treatment of multiple adja-
scaffolds in ex vivo oral wound repair. PLoS One. 2014;9:e112680.
cent GRs (TCAF), with the application of a CCM, enriched 12. Barootchi S, Tavelli L. Tunneled coronally advanced flap for the treat-
with rhPDGF-BB. The described technique is based upon ment of isolated gingival recessions with deficient papilla. Int J Esthet
site-specific application of incisions on the papillary region Dent. 2022;17:14-26.
or for the vertical release, as well as presurgical consider- 13. Tavelli L, Barootchi S. A minimally invasive approach for the treat-
ment of multiple adjacent gingival recessions with a volume-stable
ations of KTW, GT and BBD, which are assumed to be key
collagen matrix: a case series. Int J Periodontics Restorative Dent.
factors for a minimally invasive root coverage approach. 2022;42:155-162.
14. Gagnier JJ, Kienle G, Altman DG, et al. The CARE guidelines:
ACKNOWLEDGMENTS consensus-based clinical case report guideline development. J Clin
The article was self-supported. Dr. Lorenzo Tavelli has previ- Epidemiol. 2014;67:46-51.
15. Cairo F, Nieri M, Cincinelli S, Mervelt J, Pagliaro U. The interproximal
ously provided lectures sponsored by Geistlich Pharma AG,
clinical attachment level to classify gingival recessions and predict
Wolhusen, Switzerland and Lynch Biologics, Franklin, TN, root coverage outcomes: an explorative and reliability study. J Clin
USA. The collagen matrix and the growth factor utilized in Periodontol. 2011;38:661-666.
this study were kindly donated by Geistlich Pharma North 16. Barootchi S, Chan HL, Namazi SS, Wang HL, Kripfgans OD. Ultra-
America, Princeton, NJ, USA and Lynch Biologics, Franklin, sonographic characterization of lingual structures pertinent to oral,
periodontal, and implant surgery. Clin Oral Implants Res. 2020;31:352-
TN, USA, respectively. Neither company was involved in the
359.
study at any stages. 17. Tavelli L, Barootchi S, Majzoub J, et al. Ultrasonographic tissue perfu-
sion analysis at implant and palatal donor sites following soft tissue
CONFLIC TS OF INTEREST augmentation: a clinical pilot study. J Clin Periodontol. 2021;48:602-
The authors do not have any conflicts of interest pertaining 614.
18. Barootchi S, Tavelli L, Majzoub J, Chan HL, Wang HL, Kripfgans OD.
to this article.
Ultrasonographic tissue perfusion in peri-implant health and disease.
J Dent Res. 2022;101:278-285.
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