E. Todd Scheyer

Growth Factor–Mediated Treatment of Recession Defects: A Randomized Controlled Trial and Histologic and Microcomputed Tomography Examination

BACKGROUND The primary aims of this two-part prospective study were: 1) to compare the safety and efficacy of beta-tricalcium phosphate (beta-TCP) + 0.3 mg/ml recombinant human platelet-derived growth factor-BB (rhPDGF-BB) with a bioabsorbable collagen wound-healing dressing and a coronally advanced flap (CAF) to a subepithelial connective tissue graft (CTG) in combination with a CAF in subjects with gingival recession defects using a randomized, controlled, split-mouth design; and 2) to compare, through histologic and microcomputed tomography (micro-CT) examination, the periodontal regenerative potential of these two therapies in surgically created gingival recession defects in restoring missing cementum, periodontal ligament (PDL), and supporting alveolar bone. METHODS In the randomized controlled trial (RCT), 30 patients with Miller Class II buccal gingival recession, > or = 3 mm deep and > or = 3 mm wide in contralateral quadrants of the same jaw were treated and followed for 6 months. Using a split-mouth design with similar bilateral recession defects, test sites were treated with 0.3 mg/ml rhPDGF-BB + beta-TCP + bioabsorbable collagen wound-healing dressing; contralateral control sites were treated with a CTG, each in combination with a CAF. In the histologic/micro-CT study segment, recession defects were created in six teeth, each requiring extraction for orthodontic therapy. These defects were created with a recession depth > or = 3 mm, the osseous crest 2 to 3 mm apical to the gingival margin, and with 2 to 3 mm of keratinized tissue. The defects were treated with a CTG (control) or rhPDGF-BB + beta-TCP + wound-healing dressing (test), plus CAF. Nine months after surgical correction, en bloc resections were obtained and examined histologically and with micro-CT. RESULTS In the RCT, test and control treatments demonstrated clinically significant improvements from baseline through month 6. Statistically significant results favoring the CTG were found in recession depth reduction (-2.9 + 0.5 mm, test; -3.3 + 0.6 mm, control; P = 0.009), root coverage (90.8%, test; 98.6%, control; P = 0.013), and -3.9 +/- 0.7 mm, control, -3.3 +/- 1.3 mm, test, recession width reduction (P = 0.035), whereas mid-buccal probing depth (PD) and PD reduction (PDR) reduction favored the test group (1.4 +/- 0.4 mm, test; 1.8 +/- 0.1 mm, control; P < 0.001 PD and -0.0 mm test; +0.4 mm control PDR). For all other parameters, the two treatments were statistically equivalent, including increases in keratinized tissue, esthetic results, and subject satisfaction. In the histologic/micro-CT portion, all four sites treated with rhPDGF-BB + beta-TCP showed evidence of regeneration of cementum, PDL with inserting connective tissue fibers, and supporting alveolar bone, whereas neither CTG-treated site exhibited any signs of periodontal regeneration. CONCLUSIONS CTG and rhPDGF-BB + beta-TCP + wound-healing dressing are effective treatment modalities for clinically correcting gingival recession defects. In addition, the current study demonstrated that regeneration of the periodontium in gingival recession defects was possible through a growth factor-mediated approach.

Evaluation of Human Recession Defects Treated With Coronally Advanced Flaps and Either Enamel Matrix Derivative or Connective Tissue: Comparison of Clinical Parameters at 10 Years

BACKGROUND The effective treatment of gingival recession (GR) defects is crucial for predictable outcomes. The most common treatment is the subepithelial connective tissue graft (CTG), but good outcomes have also been obtained using enamel matrix derivative (EMD). A split-mouth, randomized controlled trial was previously performed during a 12-month period to evaluate primary and secondary outcomes in Miller Class I and II GR defects treated with CTG or EMD, both in combination with coronally advanced flap (CAF). The purpose of the current study is to examine the major qualitative and quantitative parameters of this study after a 10-year follow-up. METHODS Nine of 17 original patients were available for follow-up evaluation 10 years after the original surgery. The parameters measured were: (1) GR depth; (2) probing depth (PD); (3) clinical attachment level; (4) width of keratinized tissue (wKT); (5) percentage of root coverage; (6) root dentin hypersensitivity; (7) color, texture, and contour of treatment sites; and (8) patient satisfaction at 10 years. Results at 1 and 10 years of these nine patients (nine test and nine control teeth) were compared to original baseline values. In addition, results within treatment groups between 1 and 10 years and between treatment groups (i.e., EMD versus CTG) at the same time points were examined. RESULTS At 10 years, all quantitative parameters except PD for both treatment protocols showed statistically significant improvements from baseline values, including wKT in the EMD group, which at 1 year was not significantly improved compared with baseline wKT. In addition, at 10 years, there were no statistically significant differences between EMD + CAF and CTG + CAF for any measured parameter. The only statistically significant finding in this study was the difference in wKT found at 1 year (EMD, 3.00 mm; CTG, 3.89 mm; P = 0.031). Qualitative parameters at 10 years demonstrated similar stability. The only major qualitative difference was the marginal tissue contour, which was similar to adjacent tissues at EMD-treated sites but greater than adjacent tissues at all CTG sites except one. Esthetically, both EMD- and CTG-mediated treatments were similar at 10 years. However, given the choice, six of nine patients would choose EMD over CTG treatment to avoid a secondary harvesting procedure. CONCLUSIONS This paper highlights the importance of long-term data as it relates to procedural effectiveness in selecting optimally effective protocols to treat gingival recession. Based on the results of this 10-year follow-up investigation, treatment with either EMD + CAF or CTG + CAF for Miller Class I and II GR defects appears stable, clinically effective, and similar to each other on all measured parameters.

Living Cellular Construct for Increasing the Width of Keratinized Gingiva: Results From a Randomized, Within-Patient, Controlled Trial

BACKGROUND The standard of care for increasing keratinized gingiva adjacent to teeth that do not require root coverage is the free gingival graft (FGG). A pilot study indicated that the use of a living cellular construct (LCC) could be effective in this clinical scenario. METHODS A pivotal, multicenter, randomized, within-patient, controlled, open-label trial was conducted (N = 96 patients). After removing the mucosa and keratinized gingiva from the test site, either an LCC or FGG was applied. The primary efficacy endpoint was the ability of the LCC to regenerate ≥2 mm keratinized gingiva at 6 months. Secondary measures were the same color and texture as the adjacent tissue, a 1-mm width of keratinized gingiva at 6 months, patient treatment preference, surgical site sensitivity at 1 week, and patient-reported pain after 3 days. Safety was assessed by reports of adverse events. RESULTS At 6 months, the LCC regenerated ≥2 mm of keratinized gingiva in 95.3% of patients (81 of 85 patients; P <0.001 versus a 50% predefined standard). As expected, the FGG generated more keratinized gingiva than the LCC (4.57 ± 1.0 mm versus 3.2 ± 1.1 mm, respectively). The gingiva regenerated with the LCC matched the color and texture of the adjacent gingiva. All patients achieved ≥1 mm keratinized gingiva with the LCC treatment by 6 months, and more patients preferred treatment with the LCC than with the FGG. No difference in sensitivity or pain was noted between the treatments. The treatments were well tolerated, and reported adverse events were typical for this type of periodontal surgery. CONCLUSION The use of an LCC may provide a safe and effective therapy for augmenting the zone of keratinized gingiva.

Randomized, Controlled Clinical Trial to Evaluate a Xenogeneic Collagen Matrix as an Alternative to Free Gingival Grafting for Oral Soft Tissue Augmentation

BACKGROUND The standard of care for increasing keratinized tissue (KT) and vestibular area is an autogenous free gingival graft (FGG) and vestibuloplasty; however, there is morbidity associated with the harvest of autogenous tissue, and supply is limited. The purpose of this study is to determine if a xenogeneic collagen matrix (CM) might be as effective as FGG. METHODS This study is a single-masked, randomized, controlled, split-mouth study of 30 patients with insufficient zones of KT (<2 mm). It uses a within-patient treatment-comparison design to establish non-inferiority of the test (CM) versus control (FGG) therapy. The primary efficacy endpoint was change in KT width (∆KT) from surgery to 6 months post-surgery. Secondary endpoints included traditional periodontal measures, such as clinical attachment level, recession, and bleeding on probing. Patient-reported pain, discomfort, and esthetic satisfaction were also recorded. Biopsies were obtained at 6 months. RESULTS Surgery and postoperative sequelae were uneventful, with normal healing observed at both test and control sites. The primary outcome, ∆KT width at 6 months, did not establish non-inferiority of CM compared to FGG (P = 0.9992), with the FGG sites averaging 1.5 mm more KT width than CM sites. However, the amount of new KT generated for both therapies averaged ≥2 mm. Secondary outcomes were not significantly different between test and control sites. All site biopsies appeared as normal mucoperiosteum with keratinized epithelium. CM sites achieved better texture and color matches, and more than two-thirds of patients preferred the appearance of their CM sites. CONCLUSION With the proviso of sufficient KT (≈2 mm in width) and study goals of lower morbidity, unlimited supply, and patient satisfaction, CM appears to be a suitable substitute for FGG in vestibuloplasty procedures designed to increase KT around teeth.

Commentary: Incorporating Patient-Reported Outcomes in Periodontal Clinical Trials

The authors review patient-reported outcome (PRO) metrics for dentistry, and in particular, periodontics. The PRO commentary for periodontics includes a review of split-mouth, randomized, controlled clinical trial results that specifically tracked pain at different sites over time after intervention and provided guidelines for peak pain time points and evidence for referred pain assessment when studying soft tissue augmentation procedures. Both the questions that are asked of patients and the timing of those questions are important study design considerations. The authors suggest PRO methodology for periodontal clinical trials that can be used to identify information important to patients and clinicians.

Evaluation of Recession Defects Treated With Coronally Advanced Flaps and Either Recombinant Human Platelet-Derived Growth Factor-BB Plus β-Tricalcium Phosphate or Connective Tissue: Comparison of Clinical Parameters at 5 Years

BACKGROUND In a previously reported split-mouth, randomized controlled trial, Miller Class II gingival recession defects were treated with either a connective tissue graft (CTG) (control) or recombinant human platelet-derived growth factor-BB + β-tricalcium phosphate (test), both in combination with a coronally advanced flap (CAF). At 6 months, multiple outcome measures were examined. The purpose of the current study is to examine the major efficacy parameters at 5 years. METHODS Twenty of the original 30 patients were available for follow-up 5 years after the original surgery. Outcomes examined were recession depth, probing depth, clinical attachment level (CAL), height of keratinized tissue (wKT), and percentage of root coverage. Within- and across-treatment group results at 6 months and 5 years were compared with original baseline values. RESULTS At 5 years, all quantitative parameters for both treatment protocols showed statistically significant improvements over baseline. The primary outcome parameter, change in recession depth at 5 years, demonstrated statistically significant improvements in recession over baseline, although intergroup comparisons favored the control group at both 6 months and 5 years. At 5 years, intergroup comparisons also favored the test group for percentage root coverage and change in wKT, whereas no statistically significant intergroup differences were seen for 100% root coverage and changes to CAL. CONCLUSIONS In the present 5-year investigation, treatment with either test or control treatments for Miller Class II recession defects appear to lead to stable, clinically effective results, although CTG + CAF resulted in greater reductions in recession, greater percentage of root coverage, and increased wKT.

Generation of Site-Appropriate Tissue by a Living Cellular Sheet in the Treatment of Mucogingival Defects

BACKGROUND Generation of site-appropriate tissue in the oral cavity includes the restoration of the correct anatomic type, amount, and distribution of the tissue. This study is a post hoc analysis of data collected during previously published results from two randomized clinical trials of a living cellular sheet (LCS; allogenic cultured keratinocytes and fibroblasts in bovine collagen) versus a free gingival graft (FGG), evaluating their ability to augment keratinized tissue or gingiva. METHODS Post hoc histologic and clinical (photographic) comparisons of the outcomes of treatment were performed on histologic and photographic data gathered in the two randomized clinical trials. RESULTS Histologic findings showed that LCS-treated sites resembled gingiva rather than alveolar mucosa. Photographic analysis indicated that LCS treatment resulted in more site-appropriate tissue than FGG in terms of tissue color, with adjacent untreated tissue, absence of scar formation or keloid-like appearance, and mucogingival junction alignment. CONCLUSION Treatment of mucogingival defects with LCS resulted in the generation of tissue that is more site appropriate than tissue transplanted from the palate.

American Academy of Periodontology Best Evidence Consensus Statement on Selected Oral Applications for Cone-Beam Computed Tomography

BACKGROUND The American Academy of Periodontology (AAP) recently embarked on a Best Evidence Consensus (BEC) model of scientific inquiry to address questions of clinical importance in periodontology for which there is insufficient evidence to arrive at a definitive conclusion. This review addresses oral indications for use of cone-beam computed tomography (CBCT). METHODS To develop the BEC, the AAP convened a panel of experts with knowledge of CBCT and substantial experience in applying CBCT to a broad range of clinical scenarios that involve critical structures in the oral cavity. The panel examined a clinical scenario or treatment decision that would likely benefit from additional evidence and interpretation of evidence, performed a systematic review on the individual, debated the merits of published data and experiential information, developed a consensus report, and provided a clinical bottom line based on the best evidence available. RESULTS This BEC addressed the potential value and limitations of CBCT relative to specific applications in the management of patients requiring or being considered for the following clinical therapies: 1) placement of dental implants; 2) interdisciplinary dentofacial therapy involving orthodontic tooth movement in the management of malocclusion with associated risk on the supporting periodontal tissues (namely, dentoalveolar bone); and 3) management of periodontitis. CONCLUSION For each specific question addressed, there is a critical mass of evidence, but insufficient evidence to support broad conclusions or definitive clinical practice guidelines.

A Prospective, Case-Controlled Study Evaluating the Use of Enamel Matrix Derivative on Human Buccal Recession Defects: A Human Histologic Examination

BACKGROUND Connective tissue grafts (CTGs) and coronally advanced flaps (CAFs) do not regenerate periodontal attachment apparatus when used to treat gingival recessions (GRs). Instead of generating new bone, cementum, and inserting periodontal ligament fibers, CTG+CAF repairs through a long epithelial junction and connective tissue attachment. Enamel matrix derivatives (EMDs) have demonstrated proof-of-principle that periodontal regeneration can be achieved, although data are limited. METHODS Three patients, each requiring extraction of four premolars before orthodontic treatment, were enrolled in a randomized, open-label study. Two months after induction of Miller Class I and II GR, each patient received EMD+CAF for three teeth and CTG+CAF for one tooth for root coverage. Nine months after root coverage, all four premolars from each of the three patients were surgically extracted en bloc for histologic and microcomputed tomography (micro-CT) analysis, looking for evidence of periodontal regeneration. Standard clinical measurements, radiographs, and intraoral photographs were taken over prescribed time points. RESULTS Seven of the nine teeth treated with EMD+CAF demonstrated varying degrees of periodontal regeneration, detailed through histology with new bone, cementum, and inserting fibers. Micro-CT corroborated these findings. None of the three teeth treated with CTG+CAF showed periodontal regeneration. Clinical measurements were comparable for both treatments. One instance of root resorption and ankylosis was noted with EMD+CAF. CONCLUSIONS EMD+CAF continues to show histologic evidence of periodontal regeneration via human histology, this being the largest study (nine teeth) examining its effect when treating GR. The mechanism of action, ideal patient profile, and criteria leading to predictable regeneration are in need of further exploration.

Esthetic outcomes in relation to implant-abutment interface design following a standardized treatment protocol in a multicenter randomized controlled trial--a cohort of 12 cases at 1-year follow-up.

The design of an implant-abutment interface may have an impact on the peri-implant soft tissue esthetics. In an ongoing randomized controlled trial (RCT) with 141 participants, the authors evaluated the peri-implant tissue responses around three different implant-abutment interface designs used to replace single teeth in the esthetic zone. The aim of this report is to describe the treatment protocol utilized in this ongoing RCT by (1) demonstrating in detail a clinical case treated under this protocol and (2) reporting peri-implant soft tissue responses in a cohort of 12 representative cases from the RCT at 1-year follow-up. Male and female adults requiring single implants in the anterior maxilla were enrolled in the RCT according to the study protocol. Five months following any required extraction and/or socket bone grafting/ridge augmentation, one of the following three implant-abutment interfaces was placed and immediately provisionalized: (1) conical interface (CI; OsseoSpeed, Dentsply Implants), n = 4; (2) flat-to-flat interface (FI; NobelSpeedy Replace, Nobel Biocare), n = 4; or (3) platform-switch interface (PS; NanoTite Certain Prevail, Biomet 3i), n = 4. Twelve weeks later, definitive crowns were delivered. Throughout the treatment, peri-implant buccal gingival zenith height and mesial/distal papilla height were measured on stereotactic device photographs, and pink esthetic scores (PES) were determined. The demographics of the participants in each of the three implant-abutment interface groups were very similar. All 12 study sites had ideal ridge form with a minimum width of 5.5 mm following implant site development performed according to the described treatment protocol. Using this treatment protocol for single-tooth replacement in the anterior maxilla, the clinicians were able to obtain esthetic peri-implant soft tissue outcomes with all three types of implant-abutment interface designs at 1-year follow-up as shown by the Canfield data and PES. The proposed treatment protocol for single-tooth replacement in the esthetic zone provides a reliable method to obtain and assess the esthetic outcome as a function of implant-abutment interface design and is now in its fifth year of follow-up.