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.

Histologic Evidence of Oral and Periodontal Regeneration Using Recombinant Human Platelet-Derived Growth Factor.

Human histology provides critical information on the biological potential of various regenerative protocols and biomaterials, which is vital to advancing the field of periodontal regeneration, both in research and clinical practice. Outcomes of histologic studies are particularly valuable when interpreted considering additional evidence available from pre-clinical and clinical studies. One of the best-documented growth factors areproven to have positive effects on a myriad of oral regenerative procedures is recombinant human platelet-derived growth factor-BB (rhPDGF-BB). While a systematic review of clinical studies evaluating rhPDGF in oral regenerative procedures has been recently completed, a review article that focuses on the histologic outcomes is needed. Hence, this communication discusses the histologic effects of rhPDGF-BB on oral and periodontal regenerative procedures, including root coverage and soft tissue augmentation, intrabony defects, furcation defects, peri-implant bone augmentation, and guided bone regeneration. Studies from 1989 to 2022 have been included in this review.

Adaptive growth factor delivery from a polyelectrolyte coating promotes synergistic bone tissue repair and reconstruction.

Traumatic wounds and congenital defects that require large-scale bone tissue repair have few successful clinical therapies, particularly for craniomaxillofacial defects. Although bioactive materials have demonstrated alternative approaches to tissue repair, an optimized materials system for reproducible, safe, and targeted repair remains elusive. We hypothesized that controlled, rapid bone formation in large, critical-size defects could be induced by simultaneously delivering multiple biological growth factors to the site of the wound. Here, we report an approach for bone repair using a polyelectrolye multilayer coating carrying as little as 200 ng of bone morphogenetic protein-2 and platelet-derived growth factor-BB that were eluted over readily adapted time scales to induce rapid bone repair. Based on electrostatic interactions between the polymer multilayers and growth factors alone, we sustained mitogenic and osteogenic signals with these growth factors in an easily tunable and controlled manner to direct endogenous cell function. To prove the role of this adaptive release system, we applied the polyelectrolyte coating on a well-studied biodegradable poly(lactic-co-glycolic acid) support membrane. The released growth factors directed cellular processes to induce bone repair in a critical-size rat calvaria model. The released growth factors promoted local bone formation that bridged a critical-size defect in the calvaria as early as 2 wk after implantation. Mature, mechanically competent bone regenerated the native calvaria form. Such an approach could be clinically useful and has significant benefits as a synthetic, off-the-shelf, cell-free option for bone tissue repair and restoration.

Efficacy of growth factor in promoting early osseointegration.

A preclinical study was conducted to evaluate the feasibility of 2 different topical formulations of recombinant human platelet-derived growth factor-BB (rhPDGF-BB) to promote early osseointegration and enhanced bone-to-implant contact (BIC) for dental implants placed in an edentulous ridge. Six female beagle dogs were divided into 3 groups. The control group included 4 implants with no coating; test group A included 10 implants with commercially available rhPDGF-BB formulation coating; and second test group B included 10 implants with prototype viscous rhPDGF-BB coating. Three dogs were sacrificed at 3 weeks (12 implants) and the remaining 3 dogs at 6 weeks after implant placement (12 implants). The specimens were retrieved for histological evaluation, and revealed an uneventful healing of all implants without any sign of an inflammatory response at the different time intervals. Furthermore, the bone was in very close contact with the implants' surfaces with no evidence of intervening fibrous tissue layers. At 3 weeks, new bone formation between most implant threads on rhPDGF-BB coated implants was evident, whereas in the control group only a thin and sparse amount of new bone was noted. At 6 weeks, the commercially available rhPDGF-BB formulation coated implant group (Group A) showed more trabecular bone and higher BIC compared to the other 2 groups. Histologically, the results in this study showed that use of conventionally available rhPDGF-BB formulation as the implant surface treatment may accelerate the process of osseointegration and enhance BIC.

Osseointegration Foundation Charity Overdenture Program Study: Part 2.

This assessment evaluated the clinical feasibility of using narrow-diameter implants to support a mandibular overdenture. Twelve patients presenting with an edentulous mandible were recruited from nine dental offices. Each patient received two to four implants in the mandible. The implants were placed without additional bone augmentation, and a total of 36 implants were placed. All sites achieved satisfactory crestal bone stability and soft tissue maintenance 1 year after the final prosthetic restoration. This investigation was supported by the Osseointegration Foundation, working in conjunction with the Zest Anchors implant company. There are three basic valuable activities that emerge from a professional foundation, which were reflected in this case study. They include disseminating information to practitioners, persuading young clinicians to become research investigators, and reaching out to patients in need of treatment who cannot afford it without a charitable opportunity.

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.

Effect of Selective Serotonin Reuptake Inhibitor (Paroxetine) on Newly Formed Bone Volume: Real-Time In Vivo Micro-computed Tomographic Analysis.

INTRODUCTION: Selective serotonin reuptake inhibitors (SSRIs) are commonly used to treat depression and anxiety. The purpose of this study was to assess in real time the effect of paroxetine, an SSRI, on newly formed bone volume (NFBV) in standardized calvarial defects (SCDs) in rats. METHODS: Fourteen Wistar albino female rats with a mean age of 7.5 months and a mean weight of 275 g were used. The animals were randomly divided into 2 groups. The experimental group was given paroxetine 8 weeks before the surgical procedure and throughout the experiment, and the control group was given a placebo 8 weeks before the surgical procedure and throughout the experiment. In each group, 14 SCDs measuring 4.6 mm in diameter were created on the parietal bone. In both groups, a Bio-Oss + collagen membrane was placed. All defects showed primary closure. The volume of the newly formed bone (NFBV) was measured using in vivo micro-computed tomographic imaging. Measurements were taken at days 0, 14, 28, 42, and 56 after surgery using real-time assessment with micro-computed tomographic imaging. RESULTS: The mean NFBV was 17.12 ± 4.52 mm3 and 12.52 ± 4.78 mm3 for the control and experimental groups, respectively, at day 56. The differences between the 2 groups were statistically significant (P < .05) at all time intervals. CONCLUSIONS: Paroxetine intake significantly reduced the amount of regenerated NFBV and the rate of new bone formation.

Gas Plasma Treatment Improves Titanium Dental Implant Osseointegration-A Preclinical In Vivo Experimental Study.

Recent technological advancements led to the development of various plasma-based technologies for post-packaging modifications. The purpose of the present preclinical in vivo study was to assess the safety and efficacy of a novel chairside nonthermal gas plasma treatment for enhancing osseointegration of titanium implants. Six male mixed foxhounds underwent extraction of mandibular premolars and first molars, and the sockets healed for 42 days. Canine mandibles were randomized to receive either plasma-treated (test) or non-plasma-treated (control) dental implants. A total of 36 implants were placed in six animals, and they were sacrificed at 2 weeks (two animals), 4 weeks (two animals), and 6 weeks (two animals) after the implant surgery. When the radiographic analysis was performed, the changes in bone level were not statistically significant between the two groups at 2 weeks and 4 weeks. The difference became significant at 6 weeks (p = 0.016), indicating more bone loss from baseline to 6 weeks for the control group. The bone-to-implant contact (BIC) appeared to be higher for the test groups at all time points, and the BIC was significantly higher for the test group at 4 weeks (p = 0.046). In conclusion, this study underscored the potential of nonthermal plasma treatment in enhancing implant osseointegration.

Evaluation of a New Porcine Collagen Matrix for the Treatment of Buccal Gingival Recessions: A 12-Month Pilot Prospective Human Study Model.

A 12-month prospective consecutive case series study was conducted to evaluate the effectiveness of a novel porcine collagen matrix to correct moderate to severe buccogingival recession defects. A total of 10 healthy patients (8 women and 2 men; age range: 30 to 68 years) with 26 maxillary and mandibular recession gingival defects > 4 mm deep were included. Healthy maturation of gingival tissues with natural color and texture matching the adjacent soft tissue areas were observed at all reevaluation visits. Complete root coverage was not achieved in all cases, possibly due to severe buccal bone loss in most of the selected cases, which negatively impacted the results. Nevertheless, when a novel porcine collagen matrix was used, a mean root coverage of 63.15% was achieved, and gains in clinical attachment level and keratinized tissue height were seen. Future randomized clinical trials are needed to further explore the potential of porcine collagen matrix for treatment of localized gingival recession defects.

A Prospective Clinical Assessment of BioHorizons Tissue-Level Implants.

This investigation was designed to evaluate crestal bone stability and soft tissue maintenance to Laser-Lok tapered tissue-level implants. Twelve patients presenting with an edentulous site adequate for the placement of two implants were recruited from four dental offices (2 to 4 patients per office). Each patient received two Laser-Lok tissue-level implants placed with a 3-mm interimplant distance according to a surgical stent. The implants were placed so that the Laser-Lok zone sat at the junction between hard and soft tissues. A total of 24 implants were placed, and all achieved satisfactory crestal bone stability and soft tissue maintenance 1 year after receiving the final prosthetic restoration.

Human histologic evaluation of the use of the dental putty for bone formation in the maxillary sinus: case series.

A proof-of-principle study was conducted to assess the safety and efficacy of dental putty as an alternative sinus augmentation biomaterial. Six healthy patients requiring a total of 10 sinus augmentations received sinus augmentations. All patients volunteered and signed an informed consent based on the Helsinki declaration of 1975, as revised in 2000. The sinus augmentation was performed under local anesthesia with a mucoperiosteal flap elevated to expose the buccal wall of the maxillary sinus. The space was then filled with the dental putty in several increments, and the window was covered with an absorbable collagen membrane. Biopsies were harvested from all 10 treated sinuses using a 3-mm trephine bur at the time of implant placement at either 6 or at 9 months after sinus augmentation. All patients completed the study without complications, except for 1 patient who reported fistulas at 1 and 2 months after the surgery. Clinical reentry revealed that regenerated bone on the osteotomy site was soft and immature. The ground sections of the biopsied cores revealed minimum amounts of trabeculation surrounded by an abundant array of irregular-shaped residual alloplastic particles embedded in loose connective tissue. The present study's findings revealed inadequate bone formation, although the material appears to be bioinert as there is no elicitation of inflammatory response.

Osseoconduction of an Airborne Particle-Abraded and Etched Titanium Alloy Surface in Type IV Bone: A Human Histologic and Micro-CT Evaluation.

The present study aimed to evaluate the osseoconduction ability of an airborne particle-abraded and etched (SAE) titanium alloy surface when placed in humans with poor bone quality. Four patients scheduled to receive an implant-supported full-arch prosthesis received two additional reduced-diameter implants to be harvested after 6 months of submerged healing. Undecalcified vestibulopalatal/vestibulolingual histologic sections were prepared after the micro-computerized tomography (µCT) examination. Six implant sides from four biopsied implants displayed a type IV bone environment and were included in the present study. Bone-to-implant contact (BIC) was first measured on each implant side. The estimated initial BIC (E-iBIC) was evaluated by superimposing the implant profile 0.25 mm away from its actual position. The µCT provided information about the local and adjacent bony architecture. The mean BIC was 62.5% ± 10.6%, while the mean E-iBIC was 33.1% ± 4.4%. The E-iBIC/BIC ratio was 1.81 ± 0.38. The 3D µCT sections showed the thin bone trabeculae covering the implant surface; although they seemed to be separated from the rest of the bony scaffold, they were much more interconnected than what appeared to be on the 2D histologic preparations. This limited number of human histologic samples document, for the first time, that the SAE titanium alloy implant surface is apparently osseoconductive when placed in poor human bone quality. The average BIC was 1.81 times higher than the E-iBIC. This high osseoconductivity may explain the predictable clinical behavior of implants with this type of SAE textured surface in type IV bone.

Paradigm Shifts in the Evolution of Implant Therapy.

Making treatment decisions in dental implantology has evolved over the last five decades. These decisions and the clinical management of sites thereafter are selected based on recent changes, including the achievement of osseointegration, reestablishment of biologic width bone remodeling, the peri-implant soft tissue phenotype, the way peri-implantitis is defined, and advancements in digital technology. This article discusses these key aspects and their effects and influence on implant therapy.

Incidence of Sinus Membrane Perforation Using Two Types of Implant Drills: An Ex Vivo Animal Study.

This ex vivo study evaluates the incidence of sinus membrane perforation during implant site osteotomy with two different types of drills and drilling techniques. Fifty goat heads with 50 sinus pairs (100 sinus sides) were assigned to two groups (osseodensification bur [OB] group and inverse conical shape bur [ICSB] group) to simulate transcrestal sinus elevation (50 sinus sides per group). An osteotomy was performed to pass through the lateral sinus wall no more than 3 mm. The integrity of the sinus membranes was examined and confirmed under a microscope. Of the 50 sinuses per group, the OB group presented with 14 (28%) perforated sinuses, while the ICSB group presented with 2 (4%) perforated sinuses. Of the 14 perforations from the OB group, 6 (42.9%) showed a pinpoint perforation pattern, 4 (28.5%) of which were not visible until direct air pressure was applied. Overall, the ICSB drill group demonstrated a lower sinus perforation rate than the OB group.

Pilot clinical and histologic evaluations of a two-piece zirconia implant.

An investigation was conducted to evaluate the clinical and histologic results of bone and soft tissue healing around a two-piece zirconia dental implant in a human model. A healthy female patient requiring tooth replacement with dental implants received a two-piece zirconia implant together with conventional titanium implants to be implemented in a prosthesis. Clinical and radiographic evaluations at 6 months revealed stable osseointegrated zirconia and titanium dental implants. Light microscopy and backscatter scanning electron microscopic analyses confirmed the biocompatibility and achievement of osseointegration, in addition to maintenance of the crestal bone level. The findings suggest that the bone-to-implant contact with a zirconia implant surface is sufficient to provide clinical and histologic evidence of osseointegration. The biopsied two-piece zirconia dental implant with platform switching demonstrated osseointegration occlusal to the implant-abutment junction, eliminating the significance of the microgap.

The feasibility of demineralized bone matrix and cancellous bone chips in conjunction with an extracellular matrix membrane for alveolar ridge preservation: a case series.

An investigation was conducted to test the feasibility of demineralized bone matrix and cancellous bone chips in a reverse-phase medium carrier (DynaBlast) in concert with an extracellular matrix membrane (DynaMatrix) to provide hard and soft tissue regeneration for the purpose of a ridge preservation procedure. Nine patients requiring extraction of 30 maxillary teeth were grafted with DynaBlast and DynaMatrix. Twenty sites attained primary flap closure over the grafted area (primary healing intention group), while 10 sites were assigned randomly to the secondary healing intention group, in which primary flap closure over the membrane was not achieved. Clinical and radiographic evaluations at 6 months revealed comparable bone formation for both groups. Histologic analyses of 21 harvested soft and hard tissue core biopsies revealed absence of the remnant membrane and consistent patterns of new bone formation. The efficacy and safety of DynaBlast and DynaMatrix have been validated clinically and histologically to preserve the dimensions of the alveolar process.

The clinical and histologic efficacy of xenograft granules for maxillary sinus floor augmentation.

The objective of this study was to investigate the potential of xenograft (cancellous bovine bone) granules to form vital bone in non-natural bone-forming areas of maxillary sinuses. Fourteen sinus augmentations were performed in 14 patients. Surgical outcomes were uneventful, and sufficient radiopaque volume was present radiographically to place dental implants in all sites. Clinical reentry at 6 months revealed bone formation at the osteotomy site. Histologic evaluation of the obtained bone cores revealed that xenograft granules were integrated and surrounded by woven bone and lamellar bone that were in close contact with the particles. The average percentage of newly formed bone at 6 months was 27.5% ± 8.9%. Vital bone formation using the xenograft granules was supported by both clinical and histologic evidence.

A Novel Surgical Approach to Modify the Periodontal Phenotype for the Prevention of Mucogingival Complications Related to Orthodontic Treatment.

Certain bone morphologies and soft tissue thickness (ie, phenotype) are considered to be risk factors for the development of gingival recessions following orthodontic tooth movement. Preoperative evaluation of the periodontal phenotype, in the frame of orthodontic treatment plan, identify teeth at high risk for mucogingival complications related to orthodontic therapy. The new surgical technique is illustrated in a clinical case. A patient with a thin phenotype without visible gingival recession had bone dehiscences in the anterior mandible. Prior to orthodontic treatment, simultaneous bone and soft tissue augmentation was performed using the combination of a highly cross-linked ribose porcine type I collagen membrane and a subepithelial palatal connective tissue graft. Two years after augmentation surgery and initiation of orthodontic treatment, a thick buccal tissue with a wide band of attached gingiva was observed without any clinical signs of root prominences, indicating a substantial change in periodontal phenotype. The clinical findings were corroborated by the 3D analysis, demonstrating substantial bone apposition on the buccal aspect of all roots in the treated area. The described surgical technique offers a valuable approach for regenerating hard and soft tissues in deficient areas prior to orthodontic therapy, thus preventing the development of gingival recessions.

A Clinical Classification System for the Treatment of Postextraction Sites.

A postextraction socket is always open to different treatment possibilities. A straightforward clinical classification may help evaluate which surgical approach is best suited for the case being treated. Four different classes are defined on the basis of the local anatomy of the site, available bone volume, and soft tissue level. For every clinical situation, either immediate placement, early placement, alveolar ridge preservation, or staged approach can be selected as a treatment modality according to the classifications listed.