Twenty-five years of recombinant human growth factors rhPDGF-BB and rhBMP-2 in oral hard and soft tissue regeneration.

Contemporary oral tissue engineering strategies involve recombinant human growth factor approaches to stimulate diverse cellular processes including cell differentiation, migration, recruitment, and proliferation at grafted areas. Recombinant human growth factor applications in oral hard and soft tissue regeneration have been progressively researched over the last 25 years. Growth factor-mediated surgical approaches aim to accelerate healing, tissue reconstruction, and patient recovery. Thus, regenerative approaches involving growth factors such as recombinant human platelet-derived growth factor-BB (rhPDGF-BB) and recombinant human bone morphogenetic proteins (rhBMPs) have shown certain advantages over invasive traditional surgical approaches in severe hard and soft tissue defects. Several clinical studies assessed the outcomes of rhBMP-2 in diverse clinical applications for implant site development and bone augmentation. Current evidence regarding the clinical benefits of rhBMP-2 compared to conventional therapies is inconclusive. Nevertheless, it seems that rhBMP-2 can promote faster wound healing processes and enhance de novo bone formation, which may be particularly favorable in patients with compromised bone healing capacity or limited donor sites. rhPDGF-BB has been extensively applied for periodontal regenerative procedures and for the treatment of gingival recessions, showing consistent and positive outcomes. Nevertheless, current evidence regarding its benefits at implant and edentulous sites is limited. The present review explores and depicts the current applications, outcomes, and evidence-based clinical recommendations of rhPDGF-BB and rhBMPs for oral tissue regeneration.

Tooth Retention and Clinical and Radiographic Long-Term Results Among Patients Treated with the Full-Mouth Laser-Assisted New Attachment Procedure (LANAP): A Case Series.

There are limited long-term treatment results for patients who receive full-mouth laser-assisted new attachment procedure (LANAP). The present study examined cases of full-mouth LANAP therapy for tooth retention, including clinical and radiographic changes. Sixty-six generalized stage III/IV periodontitis patients aged 30 to 76 years were identified via consecutive retrospective chart reviews in a private practice limited to periodontics. Following treatment with the LANAP protocol, differences between baseline and the patient's most recent periodontal maintenance visit (mean: 6.7 years) were determined regarding interproximal probing depths (iPD) and interproximal bone loss (iBL) percentages. Factors affecting tooth loss were analyzed using Cox proportional hazard regression survival analysis. The average tooth loss for the study population was 0.11 teeth/patient/year. Premolars were more likely to be retained compared to the reference group of incisors (hazard ratio = 0.38; 95% CI = 0.16 to 0.90; P = .03), adjusting for canines, molars, and other potential confounding factors. Age at the time of LANAP treatment, gender, history of diabetes, and baseline iBL and iPD were all significantly associated with tooth loss after full-mouth LANAP treatment. Clinical changes in iPD were more significant among premolars and molars when followed up for a period of less than 7 years. Tooth retention after full-mouth LANAP treatment was favorable in this cohort of private practice patients. Int J Periodontics Restorative Dent 2023;43:181-191. doi: 10.11607/prd.6418.

American Academy of Periodontology best evidence consensus statement on the use of biologics in clinical practice.

A biologic is a therapeutic agent with biological activity that is administered to achieve an enhanced regenerative or reparative effect. The use of biologics has progressively become a core component of contemporary periodontal practice. However, some questions remain about their safety, indications, and effectiveness in specific clinical scenarios. Given their availability for routine clinical use and the existing amount of related evidence, the goal of this American Academy of Periodontology (AAP) best evidence consensus (BEC) was to provide a state-of-the-art, evidence-based perspective on the therapeutic application of autologous blood-derived products (ABPs), enamel matrix derivative (EMD), recombinant human platelet-derived growth factor BB (rhPDGF-BB), and recombinant human bone morphogenetic protein 2 (rhBMP-2). A panel of experts with extensive knowledge on the science and clinical application of biologics was convened. Three systematic reviews covering the areas of periodontal plastic surgery, treatment of infrabony defects, and alveolar ridge preservation/reconstruction and implant site development were conducted a priori and provided the foundation for the deliberations. The expert panel debated the merits of published data and exchanged experiential information to formulate evidence-based consensus statements and recommendations for clinical practice and future research. Based on an analysis of the current evidence and expert opinion, the panel concluded that the appropriate use of biologics in periodontal practice is generally safe and provides added benefits to conventional treatment approaches. However, therapeutic benefits and risks range based on the specific biologics used as well as patient-related local and systemic factors. Given the limited evidence available for some indications (e.g., gingival augmentation therapy, alveolar ridge preservation/reconstruction, and implant site development), future clinical studies that can expand the knowledge base on the clinical use of biologics in periodontal practice are warranted.

Human Clinical and Histologic Evaluations of Laser-Assisted Periodontal Therapy with a 9.3-µm CO² Laser System.

This investigation was designed to evaluate the healing response of 9.3-µm CO2 laser-assisted periodontal therapy. Five patients presenting with moderate to severe periodontitis, with an initial pocket depth (PD) ≥ 5 mm and with teeth predetermined to be surgically extracted, were enrolled and consented to treatment with full-mouth CO2 laser-assisted therapy. The laser treatment was carried out in the Ultraguide Mode at a setting of 0.25-mm spot size, with an average power of 0.65 to 1.15 watts and 20% mist. The laser tip was passed from the gingival margin and down apically to the base of the pocket with a sweeping L motion. The teeth were intensely scaled with piezoultrasonic instrumentation afterwards. A second pass of the laser tip was performed for the study teeth. At 9 months, all patients were clinically reevaluated. For sites with an initial pocket depth of ≥ 7 mm, a mean PD reduction of 3.97 ± 1.36 mm and a mean clinical attachment level gain of 3.54 ± 1.54 mm were achieved, resulting in a mean PD of 3.91 ± 0.77 mm. En bloc biopsy samples of four teeth were obtained and analyzed; two demonstrated histologic evidence of new bone formation while the other two healed with a long junctional epithelium with minimal inflammatory infiltrate. Further long-term clinical studies are needed to investigate the treatment stability obtained with a 9.3-µm CO2 laser compared to conventional surgical therapy. Nevertheless, the encouraging clinical results indicated that adjunctive use of the 9.3-µm CO2 laser-assisted periodontal therapy can be beneficial for treatment of periodontally compromised patients.

Prospective 1-Year Study of Immediately Loaded Implants: 8-Patient Case Series Report.

The goal of this case series report is to demonstrate the predictability of providing immediate restorations with an implant specifically designed to achieve high primary stability, and to report on 12-month survival outcomes. Twenty-nine implants were placed in eight patients with various tooth-replacement needs, from single teeth to partially edentulous spans to fully edentulous mandibles. A new tapered-implant system (The Marc Nevins, Little Implant) was utilized that incorporates a self-tapping thread design with a thread pitch and thread lead to improve primary stability at insertion. All implants were placed with a minimum insertion torque of 45 Ncm. Four immediate implants and two early placements at extraction sites were included in the cohort. Twenty-seven implants were clinically successful at 1 year. Two implants in a healed ridge were found to have failed at 6 weeks postoperative in one patient wearing an ill-fitting removable partial denture. The radiographic crestal marginal bone levels were recorded in millimeters from the top of the implant platform to the first bone-to-implant contact. The mean crestal marginal bone level change was -0.57 ± 0.82 mm. This case series report demonstrates the ability of an implant designed for high primary stability to achieve successful integration in the presence of an immediate restoration for various clinical presentations, including single-tooth, multi-unit, and edentulous cases.

Late Dental Implant Failures Associated with Retained Root Fragments: Case Reports with Histologic and SEM Analysis.

Interest has recently developed in the purposeful retention of root fragments with their periodontal apparatus to support bone and soft tissue at immediate implant sites in the esthetic zone. This methodology is designed to avoid bone grafting, connective tissue grafts, and the use of membranes and may have short-term benefits in terms of tissue preservation. However, it is not completely without long-term risks. At times, implants may be unintentionally placed into edentulous sites where root fragments remain. This report presents two cases of long-term failure postloading associated with unintentionally retained root fragments. Histologic evaluation evidenced retained root fragments in close association with dental implants and the surrounding bone. Scanning electron microscopic evaluation revealed that the failed implant surfaces were infiltrated by bacterial deposits and calculus. Clinicians should exercise caution when placing dental implants in sites with retained root fragments, as long-term risks may be associated with this therapy.

Minimally invasive esthetic ridge preservation with growth-factor enhanced bone matrix.

OBJECTIVES: Extraction socket preservation procedures are critical to successful esthetic implant therapy. Conventional surgical approaches are technique sensitive and often result in alteration of the soft tissue architecture, which then requires additional corrective surgical procedures. This case series report presents the ability of flapless surgical techniques combined with a growth factor-enhanced bone matrix to provide esthetic ridge preservation at the time of extraction for compromised sockets. CLINICAL CONSIDERATIONS: When considering esthetic dental implant therapy, preservation, or further enhancement of the available tissue support at the time of tooth extraction may provide an improved esthetic outcome with reduced postoperative sequelae and decreased treatment duration. Advances in minimally invasive surgical techniques combined with recombinant growth factor technology offer an alternative for bone reconstruction while maintaining the gingival architecture for enhanced esthetic outcome. The combination of freeze-dried bone allograft (FDBA) and rhPDGF-BB (platelet-derived growth factor-BB) provides a growth-factor enhanced matrix to induce bone and soft tissue healing. CONCLUSIONS: The use of a growth-factor enhanced matrix is an option for minimally invasive ridge preservation procedures for sites with advanced bone loss. Further studies including randomized clinical trials are needed to better understand the extent and limits of these procedures. CLINICAL SIGNIFICANCE: The use of minimally invasive techniques with growth factors for esthetic ridge preservation reduces patient morbidity associated with more invasive approaches and increases the predictability for enhanced patient outcomes. By reducing the need for autogenous bone grafts the use of this technology is favorable for patient acceptance and ease of treatment process for esthetic dental implant therapy.

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 randomized, controlled, multicentre clinical trial of post-extraction alveolar ridge preservation.

AIM: To compare the effectiveness of two-ridge preservation treatments. MATERIALS AND METHODS: Forty subjects with extraction sockets exhibiting substantial buccal dehiscences were enrolled and randomized across 10 standardized centres. Treatments were demineralized allograft plus reconstituted and cross-linked collagen membrane (DFDBA + RECXC) or deproteinized bovine bone mineral with collagen plus native, bilayer collagen membrane (DBBMC + NBCM). Socket dimensions were recorded at baseline and 6 months. Wound closure and soft tissue inflammation were followed post-operatively, and biopsies were retrieved for histomorphometric analysis at 6 months. RESULTS: Primary endpoint: at 6 months, extraction socket horizontal measures were significantly greater for DBBMC + NBCM (average 1.76 mm greater, p = 0.0256). Secondary and Exploratory endpoints: (1) lingual and buccal vertical bone changes were not significantly different between the two treatment modalities, (2) histomorphometric % new bone and % new bone + graft were not significantly different, but significantly more graft remnants remained for DBBMC; (3) at 1 month, incision line gaps were significantly greater and more incision lines remained open for DFDBA + RECXC; (4) higher inflammation at 1 week tended to correlate with lower ridge preservation results; and (5) deeper socket morphologies with thinner bony walls correlated with better ridge preservation. Thirty-seven of 40 sites had sufficient ridge dimension for implant placement at 6 months; the remainder were DFDBA + RECXC sites. CONCLUSION: DBBMC + NBCM provided better soft tissue healing and ridge preservation for implant placement. Deeper extraction sockets with higher and more intact bony walls responded more favourably to ridge preservation therapy.

Surgical Management of Significant Maxillary Anterior Vertical Ridge Defects.

Severe vertical ridge deficiency in the anterior maxilla represents one of the most challenging scenarios in bone regeneration. Under ideal circumstances, guided bone regeneration in combination with soft tissue management has shown predictable esthetic and functional outcomes. Success largely relies on primary wound closure during and after the surgical procedure. Surgical sites present different challenges that need to be considered when designing the flap. The goal of this article is to propose a classification of flap designs that considers vestibular depth and scar formation around the periosteum when performing vertical ridge augmentation in the atrophic anterior maxilla. The four clinical conditions proposed under this classification are (1) shallow vestibule with healthy periosteum, (2) deep vestibule with healthy periosteum, (3) shallow vestibule with scarred periosteum, and (4) deep vestibule with scarred periosteum. The classification will allow clinicians to achieve tension-free closure and more predictable vertical bone gain.

Periodontal regeneration - intrabony defects: a consensus report from the AAP Regeneration Workshop.

BACKGROUND: Treatment of intrabony defects is an important therapeutic goal of periodontal therapy. The goal of this consensus report was to critically appraise the evidence for the available approaches for promoting periodontal regeneration in intrabony defects. In addition to evaluating the effectiveness of new regenerative approaches for intrabony defects, recommendations for future research were defined for this area. METHODS: A systematic review was conducted using computerized searches of PubMed and Cochrane databases, supplemented with screening of references in original reports, review articles, and a hand search in selected journals. All searches were focused on regenerative approaches with histologic evidence of periodontal regeneration (proof of principle), clinical trials, and case reports. For purposes of analysis, change in intrabony defect fill was considered the primary outcome variable, with change in clinical attachment as a secondary outcome. The SORT (Strength of Recommendation Taxonomy) grade was used to evaluate the quality and strength of the evidence. During the consensus meeting, the group agreed on the outcomes of the systematic review, pertinent sources of evidence, clinical recommendations, and areas requiring future research. RESULTS: The systematic review, which was conducted for the consensus conference, evaluated the effectiveness of the use of biologics for the treatment of intrabony defects. Enamel matrix derivative (EMD) and recombinant human platelet-derived growth factor-BB (rhPDGF-BB) with ß-tricalcium phosphate were shown to be efficacious in regenerating intrabony defects. The level of evidence is supported by multiple studies documenting effectiveness. The clinical application of biologics supports improvements in clinical parameters comparable with selected bone replacement grafts and guided tissue regeneration (GTR). Factors negatively affecting regeneration included smoking and excessive tooth mobility. CONCLUSIONS: Periodontal regeneration in intrabony defects is possible on previously diseased root surfaces, as evidenced by a gain in clinical attachment, decreased pocket probing depth, gain in radiographic bone height, and overall improvement in periodontal health. These clinical findings are consistent with available histologic evidence. Clinical improvements can be maintained over long periods (>10 years). Although bone replacement grafts have been the most commonly investigated modality, GTR, biologics, and combination therapies have also been shown to be effective. Future research should emphasize patient-reported outcomes, individual response differences, and emerging technologies to enhance treatment results. CLINICAL RECOMMENDATIONS: Early management of intrabony defects with regenerative therapies offers the greatest potential for successful periodontal regeneration. The clinical selection and application of a regenerative therapy or combination of therapies for periodontal regeneration should be based on the clinician's experiences and understanding of the regenerative biology and technology. This decision-making process should take into consideration the potential adverse influence of factors, such as smoking, poor oral hygiene, tooth mobility, and defect morphology, on regeneration. Management should be coupled with an effective maintenance program for long-term success.

Periodontal Regeneration - Intrabony Defects: Practical Applications From the AAP Regeneration Workshop.

Focused Clinical Question: What are important considerations for selecting a predictable regenerative surgical approach for intrabony defects? Summary: The predictable regeneration of intrabony defects remains an important goal in the management of periodontitis. Clinical and histologic evidence of periodontal regeneration has been shown for multiple regenerative therapies, including bone replacement grafts, guided tissue regeneration, and biologics, when used alone or in combination. Regenerative therapies improve periodontal health, as evidenced by gains in clinical attachment level, reductions in probing depth, and gains in radiographic bone fill. Important patient-related factors (e.g., smoking) and defect/site-related factors (e.g., defect morphology and gingival biotype) can influence the potential to achieve periodontal regeneration. The regeneration of intrabony defects generally becomes more challenging with increasing loss of height, proximity, and number of bony walls. Therefore, combination therapies may be necessary to achieve predictable regeneration. Clinical improvements after regenerative therapy can be maintained over extended periods (≥10 years) with professional maintenance at appropriate intervals and adequate home care. Conclusions: Periodontal regeneration of intrabony defects is possible using a variety of regenerative strategies. Management should be coupled with an effective oral hygiene and supportive periodontal maintenance program for long-term success.

Use of Er:YAG laser to decontaminate infected dental implant surface in preparation for reestablishment of bone-to-implant contact.

The prevalence of peri-implantitis is of concern to all clinicians participating in implant dentistry. Peri-implant inflammation results in the loss of supporting bone for the implant that may or may not be accompanied by bleeding on probing and suppuration. Early diagnosis and intervention are mandated, but there is a paucity of evidence leading to the most effective therapy. There is agreement that one of the challenges in surgically treating peri-implant defects is the process of cleaning and decontaminating the implant surface, which may be contaminated by bacterial aggregates. This preclinical canine study investigates the erbium:yttrium-aluminum-garnet laser to decontaminate the complex rough surface of the implant by stripping the contaminated oxide layer for induction of hard and soft tissue adaptation to a compromised or failing implant. The results provide evidence of new bone-to-implant contact established at a level representative of the size of the defects. The soft tissues contain little or no evidence of inflammation, which can be interpreted as an arrest of the disease progression process. The results can be translated to a treatment goal of stabilizing the prognosis of an implant that has been compromised.

Platform switching versus conventional technique: a randomized controlled clinical trial.

In this controlled prospective study, 53 patients treated at four study centers were randomly assigned to receive either (test) implants with platform switching built into their design or similar nonplatform-switched controls (same manufacturer, surface treatment, etc) for treatment of single and multiple edentulous sites in all four quadrants. Radiographs taken at the time of implant placement, definitive restoration delivery, and 1-year follow-up found significantly less crestal bone loss around the test implants (0.25 mm) compared to the controls (0.65 mm). Notably, bone loss around the control implants had declined by the 1-year follow-up point.

Recombinant human platelet-derived growth factor BB for reconstruction of human large extraction site defects.

This study investigated the ability of growth factor-enhanced matrices combined with a tenting screw scaffolding system and resorbable membrane to regenerate large alveolar extraction site defects. Eight patients were randomized to treatment either with a bovine or equine matrix mixed in a ratio of 1.0 mL (0.3 mg/mL) recombinant human platelet-derived growth factor BB (rh-PDGF-BB) per gram of xenograft and allowed to absorb for 10 minutes. Tenting screws were used to provide additional support, and the growth factor-enhanced particulate matrix was incrementally placed and condensed into the defect and covered by a resorbable membrane. Reentry surgery after 5 months allowed for trephine core biopsies and implant placement. All sites healed well with evidence of bonelike hard tissue that was confirmed histologically as vital bone around the remaining graft particulate in both treatment groups. The results of this study demonstrate the capability of growth factor-enhanced matrices combined with tenting screws and a resorbable membrane to support the reconstruction of large extraction site defects.

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.

A prospective, randomized controlled preclinical trial to evaluate different formulations of biphasic calcium phosphate in combination with a hydroxyapatite collagen membrane to reconstruct deficient alveolar ridges.

Many patients and clinicians would prefer a synthetic particulate bone replacement graft, but most available alloplastic biomaterials have limited osteogenic potential. An alloplast with increased regenerative capacity would be advantageous for the treatment of localized alveolar ridge defects. This prospective, randomized controlled preclinical trial utilized 6 female foxhounds to analyze the osteogenic impact of different formulations of biphasic calcium phosphate (BCP) in combination with an hydroxyapatite-collagen membrane and their ability to reconstruct deficient alveolar ridges for future implant placement. The grafted sites were allowed to heal 3 months, and then trephine biopsies were obtained to perform light microscopic and histomorphometric analyses. All treated sites healed well with no early membrane exposure or adverse soft tissue responses during the healing period. The grafted sites exhibited greater radiopacity than the surrounding native bone with BCP particles seen as radiopaque granules. The graft particles appeared to be well-integrated and no areas of loose particles were observed. Histologic evaluation demonstrated BCP particles embedded in woven bone with dense connective tissue/marrow space. New bone growth was observed around the graft particles as well as within the structure of the graft particulate. There was intimate contact between the graft particles and newly formed bone, and graft particles were bridged by the newly formed bone in all biopsies from the tested groups. The present study results support the potential of these BCP graft particulates to stimulate new bone formation. Clinical studies are recommended to confirm these preclinical findings.

The clinical and histologic outcome of dental implant in large ridge defect regenerated with alloplast: a randomized controlled preclinical trial.

A basic tenet of successful osseointegration is that the implant resides in a sufficient quality and quantity of bone to ensure bone contact and thus stabilization. A prospective, randomized controlled preclinical trial was conducted to evaluate the bone-to-implant contact (BIC) when placing implants in bone regenerated by 3 different combinations of biphasic calcium phosphate (BCP). Dental implants were placed into the regenerated ridges of 6 female foxhounds; the ridges were reconstructed with different formulations of BCP in combination with an hydroxyapatite collagen membrane. They were retrieved after 3 months to perform light microscopic and histomorphometric analyses. Implants in each group appeared to be stable and osseointegrated. Light microscopic evaluation revealed tight contacts between the implant threads with the surrounding bone for all 4 groups. The mean BIC ranged from 64.7% to 73.7%. This preclinical trial provided clinical and histologic evidence to support the efficacy of all 3 formulations of BCP to treat large alveolar ridge defects to receive osseointegrated dental implants.