The combination of purified recombinant human platelet-derived growth factor-BB and equine particulate bone graft for periodontal regeneration

Background: The objective of this study is to evaluate the potential for periodontal regeneration of a critical‐sized defect with the application of recombinant human platelet‐derived growth factor (rhPDGF‐BB) combined with either a particulate equine or a β‐tricalcium phosphate (β‐TCP) matrix. Methods: Critical‐sized intrabony 2‐wall defects were created bilaterally on the distal surface of the second premolar and the mesial surface of the first molar in nine hounds. Twelve defects received rhPDGF‐BB/equine treatment, 12 defects received rhPDGF‐BB/β‐TCP treatment, and the remaining 12 sites served as sham‐surgery controls. The animals were sacrificed after a 10‐week healing period. Results: Clinical healing was uneventful without obvious signs of overt gingival inflammation. Histologic and histomorphometric analyses revealed statistically that there were differences among the three groups in terms of new bone formation (P <0.001). The amount of test material for both rhPDGF‐BB/equine and rhPDGF‐BB/β‐TCP groups was comparable, but the amount of newly formed bone was significantly higher (P <0.01) in favor of the rhPDGF‐BB/equine group. The amount of new cementum formed for the rhPDGF‐BB/equine group (4.8 ± 1.3 mm) was significantly higher (P =0.001) than the sham‐surgery control group (1.7 ± 1.9 mm). Conclusion: Both rhPDGF‐BB/equine and rhPDGF‐BB/β‐TCP have the potential to support the regeneration of the periodontal attachment apparatus.     

Introduction of a Mixture of β‐Tricalcium Phosphate Into a Complex of Bone Marrow Mesenchymal Stem Cells and Type I Collagen Can Augment the Volume of Alveolar Bone Without Impairing Cementum Regeneration

Background: The purpose of this study is to evaluate whether β‐tricalcium phosphate (β‐TCP) could be a promising modality to help augment alveolar bone in periodontal tissue regeneration by bone marrow mesenchymal stem cells (BMMSCs). Methods: Expanded BMMSCs and atelocollagen (Col) were mixed together (MSC/Col). A combination of β‐TCP with MSC/Col was also prepared (MSC/Col/TCP). MSC/Col/TCP or MSC/Col was transplanted into experimental periodontal Class III furcation defects that had been exposed to inflammation in beagle dogs. Periodontal tissue regeneration was evaluated by histologic and morphometric analyses at 4 and 8 weeks after transplantation. Results: MSC/Col and MSC/Col/TCP enhanced periodontal tissue regeneration compared to Col and TCP/Col according to hematoxylin and eosin staining. The percentage of new cementum length in the MSC/Col/TCP group was not significantly different from that in the MSC/Col group at 4 and 8 weeks. On the other hand, the percentage of new bone area in the MSC/Col/TCP group was much higher than that in the MSC/TCP group at 4 weeks. However, at 8 weeks, no significant difference in new bone area was found between the two groups. In the MSC/Col/TCP group, β‐TCP was surrounded by newly formed bone. Multinucleated cells, which were positive for osteopontin and tartrate‐resistant acid phosphatase, were present in the interconnected macropores of β‐TCP. Conclusion: These findings suggest that β‐TCP is applicable as a scaffold for BMMSCs transplantation and helps augment alveolar bone without impairing regeneration of cementum.     

Platelet‐Derived Growth Factor Promotes Periodontal Regeneration in Localized Osseous Defects: 36‐Month Extension Results From a Randomized,Controlled, Double‐Masked Clinical Trial

Background: Recombinant human platelet‐derived growth factor (rhPDGF) is safe and effective for the treatment of periodontal defects in short‐term studies up to 6 months in duration. We now provide results from a 36‐month extension study of a multicenter, randomized, controlled clinical trial evaluating the effect and long‐term stability of PDGF‐BB treatment in patients with localized severe periodontal osseous defects. Methods: A total of 135 participants were enrolled from six clinical centers for an extension trial. Eighty‐three individuals completed the study at 36 months and were included in the analysis. The study investigated the local application of β‐tricalcium phosphate scaffold matrix with or without two different dose levels of PDGF (0.3 or 1.0 mg/mL PDGF‐BB) in patients possessing one localized periodontal osseous defect. Composite analysis for clinical and radiographic evidence of treatment success was defined as percentage of cases with clinical attachment level (CAL) ≥2.7 mm and linear bone growth (LBG) ≥1.1 mm. Results: The participants exceeding this composite outcome benchmark in the 0.3 mg/mL rhPDGF‐BB group went from 62.2% at 12 months, 75.9% at 24 months, to 87.0% at 36 months compared with 39.5%, 48.3%, and 53.8%, respectively, in the scaffold control group at these same time points (P <0.05). Although there were no significant increases in CAL and LBG at 36 months among all groups, there were continued increases in CAL gain, LBG, and percentage bone fill over time, suggesting overall stability of the regenerative response. Conclusion: PDGF‐BB in a synthetic scaffold matrix promotes long‐term stable clinical and radiographic improvements as measured by composite outcomes for CAL gain and LBG for patients possessing localized periodontal defects ( ClinicalTrials.gov no. CT01530126).     

Comparison Between a β‐Tricalcium Phosphate and an Absorbable Collagen Sponge Carrier Technology for rhGDF‐5–Stimulated Periodontal Wound Healing/Regeneration

Background: The objective of this study is to compare a candidate β‐tricalcium phosphate (β‐TCP) carrier technology with the absorbable collagen sponge (ACS) benchmark to support recombinant human growth/differentiation factor‐5 (rhGDF‐5)–stimulated periodontal wound healing/regeneration. Methods: Routine, bilateral, critical‐size (5‐mm), 1‐wall, intrabony periodontal defects were surgically created in the mandibular premolar region in 10 beagle dogs. Five animals received rhGDF‐5/β‐TCP and five animals received rhGDF‐5/ACS, with a total of 20 μg rhGDF‐5 per defect. The animals were euthanized for histologic and histometric analyses at 8 weeks postsurgery. Results: Both rhGDF‐5/ACS and rhGDF‐5/β‐TCP stimulated the formation of functionally oriented periodontal ligament, cellular mixed fiber cementum, and woven/lamellar bone. Bone regeneration (height and area) was significantly greater for the rhGDF‐5/β‐TCP construct than for the rhGDF‐5/ACS (3.26 ± 0.30 mm versus 2.22 ± 0.82 mm, P <0.01; and 10.45 ± 2.26 mm² versus 5.62 ± 2.39 mm², P <0.01, respectively). Cementum formation ranged from 3.83 ± 0.73 mm to 3.03 ± 1.18 mm without significant differences between groups. Root resorption/ankylosis was not observed. Conclusions: The β‐TCP carrier technology significantly enhanced rhGDF‐5–stimulated bone formation compared with the ACS benchmark in this discriminating periodontal defect model. The structural integrity of the β‐TCP carrier, preventing compression while providing a framework for bone ingrowth, may account for the observed results.     

Vertical ridge augmentation using an equine bone and collagen block infused with recombinant human platelet-derived growth factor-BB: a randomized single-masked histologic study in non-human primates

Background: This study tests the effectiveness of hydroxyapatite and collagen bone blocks of equine origin (eHAC), infused with recombinant human platelet‐derived growth factor‐BB (rhPDGF‐BB), to augment localized posterior mandibular defects in non‐human primates (Papio hamadryas). Methods: Bilateral critical‐sized defects simulating severe atrophy were created at the time of the posterior teeth extraction. Test and control blocks (without growth factor) were randomly grafted into the respective sites in each non‐human primate. Results: All sites exhibited vertical ridge augmentation, with physiologic hard‐ and soft‐tissue integration of the blocks when clinical and histologic examinations were done at 4 months after the vertical ridge augmentation procedure. There was a clear, although non‐significant, tendency to increased regeneration in the test sites. As in the first two preclinical studies in this series using canines, experimental eHAC blocks infused with rhPDGF‐BB proved to be a predictable and technically viable method to predictably regenerate bone and soft tissue in critical‐sized defects. Conclusion: This investigation supplies additional evidence that eHAC blocks infused with rhPDGF‐BB growth factor is a predictable and technically feasible option for vertical augmentation of severely resorbed ridges.     

Biomaterials for promoting periodontal regeneration in human intrabony defects: a systematic review

Intrabony periodontal defects are a frequent complication of periodontitis and, if left untreated, may negatively affect long‐term tooth prognosis. The optimal outcome of treatment in intrabony defects is considered to be the absence of bleeding on probing, the presence of shallow pockets associated with periodontal regeneration (i.e. formation of new root cementum with functionally orientated inserting periodontal ligament fibers connected to new alveolar bone) and no soft‐tissue recession. A plethora of different surgical techniques, often including implantation of various types of bone graft and/or bone substitutes, root surface demineralization, guided tissue regeneration, growth and differentiation factors, enamel matrix proteins or various combinations thereof, have been employed to achieve periodontal regeneration. Despite positive observations in animal models and successful outcomes reported for many of the available regenerative techniques and materials in patients, including histologic reports, robust information on the degree to which reported clinical improvements reflect true periodontal regeneration does not exist. Thus, the aim of this review was to summarize, in a systematic manner, the available histologic evidence on the effect of reconstructive periodontal surgery using various types of biomaterials to enhance periodontal wound healing/regeneration in human intrabony defects. In addition, the inherent problems associated with performing human histologic studies and in interpreting the results, as well as certain ethical considerations, are discussed. The results of the present systematic review indicate that periodontal regeneration in human intrabony defects can be achieved to a variable extent using a range of methods and materials. Periodontal regeneration has been observed following the use of a variety of bone grafts and substitutes, guided tissue regeneration, biological factors and combinations thereof. Combination approaches appear to provide the best outcomes, whilst implantation of alloplastic material alone demonstrated limited, to no, periodontal regeneration.     

Growth and differentiation factors for periodontal regeneration: a review on factors with clinical testing

Stavropoulos A, Wikesjö UME. Growth and differentiation factors for periodontal regeneration: a review on factors with clinical testing. J Periodont Res 2012; 47: 545–553. © 2012 John Wiley & Sons A/S Background and Objective: A large body of evidence implies that growth and differentiation factors, based on their ability to regulate various functions of cells originating in the periodontal tissues, may support periodontal wound healing/regeneration, creating an environment conducive to and/or immediately inducing de novo tissue formation. This study presents a short systematic overview on growth and differentiation factor technologies evaluated in the clinic for their potential to enhance periodontal wound healing/regeneration. Material and Methods: Reports on growth and differentiation factor technologies evaluated in the clinic for their potential to enhance periodontal wound healing/regeneration were selected for review. Results: Growth and differentiation factor technologies intended for periodontal wound healing/regeneration and evaluated clinically included platelet‐derived growth factor, insulin‐like growth factor‐I and ‐II, basic fibroblast growth factor, bone morphogenetic protein‐3 and growth differentiation factor‐5; platelet‐derived growth factor was the only Food and Drug Administration‐approved commercially available growth and differentiation factor technology. In general, enhanced periodontal regeneration was observed in sites receiving growth and differentiation factors compared with control(s). However, improvements of relatively limited clinical magnitude have been shown thus far. Conclusion: Although growth and differentiation factors project considerable appeal as candidate technologies in support of periodontal wound healing/regeneration, current candidate and commercially available technologies enhance treatment outcomes only to a limited extent in clinical settings.     

Initial pattern of angiogenesis and bone formation following lateral ridge augmentation using rhPDGF and guided bone regeneration: an immunohistochemical study in dogs

Objectives: To evaluate (i) the effects of rhPDGF‐BB on localized ridge augmentation using a natural bone mineral (NBM), and (ii) the influence of a collagen membrane (CM) on factor activity. Materials and methods: Chronic‐type alveolar ridge defects (n=4 dogs) were randomly allocated in a split‐mouth design as follows: upper jaw: NBM+rhPDGF‐BB+CM (test) vs. NBM+rhPDGF‐BB (control), and lower jaw: NBM+rhPDGF‐BB+CM (test) vs. NBM+CM (control). After 3 weeks, dissected blocks were prepared for immunohistochemical (angiogenesis – TG) and histomorphometrical analysis [e.g. augmented area (AA), mineralized – (MT), non‐mineralized tissue (NMT) (mm²)]. Results: Lower jaw: TG and mineralization of AA mainly originated from the defect borders. Test sites revealed a pronounced TG antigen reactivity and higher AA and MT values (mean and median). Upper jaw: control sites revealed a dislocation of AA in caudal direction, but also an improved vascularization in the peripheral wound area. While MT values (median) appeared to be comparable in both groups, AA, NMT, and NBM values (mean and median) tended to be higher at test sites. Conclusions: It was concluded that (i) rhPDGF‐BB soak‐loaded on NBM might have the potential to support bone formation at chronic‐type lateral ridge defects, and (ii) the application of CM did not seem to interfere with the factor activity, but ensured a stabilization of the graft particles. To cited this article:
Schwarz F, Ferrari D, Podolsky L, Mihatovic I, Becker J. Initial pattern of angiogenesis and bone formation following lateral ridge augmentation using rhPDGF and guided bone regeneration: an immunohistochemical study in dogs.
Clin. Oral Impl. Res. 21 , 2010; 90–99.     

The effect of smoking on periodontal bone regeneration: a systematic review and meta-analysis

Background: The effect of smoking on soft tissues after periodontal treatment has been extensively studied. However, little focus has been placed on the impact of smoking on bone regeneration after treatment. The aim of this review is to systematically assess the effect of smoking on bone regeneration after periodontal treatment. Methods: A protocol was established and studies were sourced from five electronic databases. Screening, data abstraction, and quality assessment was conducted by two review authors. Prospective and retrospective clinical studies assessing bone regeneration in smokers and non‐smokers after periodontal therapy were selected. In addition, arms of clinical trials comparing different interventions that reported results separately for smokers and non‐smokers were also included. Primary outcome measures were based on clinical and/or radiographic indicators of bone regeneration after periodontal therapy. The review and meta‐analysis followed many of the recommendations outlined in the preferred reporting items for systematic reviews and meta‐analyses statement. Results: Six of 10 studies included in this review concluded that smoking negatively influenced bone regeneration. A meta‐analysis of a subgroup of three studies demonstrated that smoking resulted in significantly less bone gain (P = 0.03) as measured by a change in the probing bone level after the treatment of intrabony defects with guided tissue regeneration. The meta‐analysis showed a standardized mean difference of ?2.05 (95% confidence interval: ?2.64 to ?1.47) using the random‐effects model. Conclusions: Smoking has a negative effect on bone regeneration after periodontal treatment. Patients should be advised that their smoking habit may result in poorer bone regeneration after periodontal treatment.     

Sinus floor augmentation with recombinant human growth and differentiation factor-5 (rhGDF-5): a histological and histomorphometric study in the Goettingen miniature pig

Aim: The aim of this study was to test the hypothesis that recombinant human growth and differentiation factor‐5 (rhGDF‐5) enhances bone formation in sinus floor augmentations in miniature pigs. Material and methods: The maxillary sinus floors in 12 adult female Goettingen minipigs were augmented with β‐tricalcium phosphate (β‐TCP) on one side. The contralateral test side was augmented using two concentrations of rhGDF‐5 (400 μg rhGDF‐5/g β‐TCP; 800 μg rhGDF‐5/g β‐TCP) delivered on β‐TCP (six animals each). One dental implant was inserted into each sinus floor augmentation. After 4 and 12 weeks, histological and histomorphometric assessment of non‐decalcified histological specimens was performed. Results: The results showed significantly higher mean values of volume density (VD) of newly formed bone using the concentration of 400 μg/g β‐TCP (22.8%) compared with the respective control (8%) after 4 weeks (P=0.05). The bone‐to‐implant contact rates were also significantly enhanced after 4 weeks between test sites (400 μg: 41.9%; 800 μg: 40.6%) and control sites (400 μg: 7.8%; 800 μg: 16.4%) (400 μg: P=0.024; 800 μg: P=0.048). Conclusion: It is concluded that rhGDF‐5 delivered on β‐TCP significantly enhanced early bone formation compared with β‐TCP alone in sinus lift procedures in miniature pigs.     

Tissue engineering for periodontal regeneration

As a result of periodontal regeneration research, a series of clinical techniques have emerged that permit tissue engineering to be performed for more efficient regeneration and repair of periodontal defects and improved implant site development. Historically, periodontal regeneration research has focused on a quest for "magic filler" material. This search has led to the development of techniques utilizing autologous bone and bone marrow, allografts, xenografts, and various man-made bone substitutes. Though these techniques have had limited success, the desire for a more effective regenerative approach has resulted in the development of tissue engineering techniques. Tissue engineering is a relatively new field of reconstructive biology which utilizes mechanical, cellular, or biologic mediators to facilitate reconstruction/regeneration of a particular tissue. In periodontology, the concept of tissue engineering had its beginnings with guided tissue regeneration, a mechanical approach utilizing nonresorbable membranes to obtain regeneration in defects. In dental implantology, guided bone regeneration membranes +/- mechanical support are used for bone augmentation of proposed implant placement sites. With the availability of partially purified protein mixture from developing teeth and growth factors from recombinant technology, a new era of tissue engineering whereby biologic mediators can be used for periodontal regeneration. The advantage of recombinant growth factors is this tissue engineering device is consistent in its regenerative capacity, and variations in regenerative response are due to individual healing response and/or poor surgical techniques. In this article, the authors review how tissue engineering has advanced and discuss its impact on the clinical management of both periodontal and osseous defects in preparation for implant placement. An understanding of these new tissue engineering techniques is essential for comprehending today's ever-expanding oral plastic surgery procedures.     

Efficacy of stem cells on periodontal regeneration: Systematic review of pre‐clinical studies

This systematic review aims to evaluate mesenchymal stem cells (MSC) periodontal regenerative potential in animal models. MEDLINE, EMBASE and LILACS databases were searched for quantitative pre‐clinical controlled animal model studies that evaluated the effect of local administration of MSC on periodontal regeneration. The systematic review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta‐Analyses statement guidelines. Twenty‐two studies met the inclusion criteria. Periodontal defects were surgically created in all studies. In seven studies, periodontal inflammation was experimentally induced following surgical defect creation. Differences in defect morphology were identified among the studies. Autogenous, alogenous and xenogenous MSC were used to promote periodontal regeneration. These included bone marrow‐derived MSC, periodontal ligament (PDL)‐derived MSC, dental pulp‐derived MSC, gingival margin‐derived MSC, foreskin‐derived induced pluripotent stem cells, adipose tissue‐derived MSC, cementum‐derived MSC, periapical follicular MSC and alveolar periosteal cells. Meta‐analysis was not possible due to heterogeneities in study designs. In most of the studies, local MSC implantation was not associated with adverse effects. The use of bone marrow‐derived MSC for periodontal regeneration yielded conflicting results. In contrast, PDL‐MSC consistently promoted increased PDL and cementum regeneration. Finally, the adjunct use of MSC improved the regenerative outcomes of periodontal defects treated with membranes or bone substitutes. Despite the quality level of the existing evidence, the current data indicate that the use of MSC may provide beneficial effects on periodontal regeneration. The various degrees of success of MSC in periodontal regeneration are likely to be related to the use of heterogeneous cells. Thus, future studies need to identify phenotypic profiles of highly regenerative MSC populations.     

New regenerative technologies: rationale and potential for periodontal regeneration: 2. Growth factors

Regenerative techniques have been clinically available for over a decade, although success in promoting new bone, cementum and connective tissue attachment has been limited. New understanding of the tissues involved in regeneration, and of the materials used to promote regeneration, have led to new advances. This is the second of two articles discussing new regenerative technologies with respect to their rationale and potential for periodontal regeneration. This article focuses on growth factors, and in particular bone morphogenetic proteins.     

Long‐Term Evaluation of Periodontal Parameters and Implant Outcomes in Periodontally Compromised Patients: A Systematic Review

Background : The aim of this systematic review is to evaluate the long‐term outcomes of patients with periodontitis submitted to periodontal therapy/maintenance and implant placement. Methods: Studies reporting clinical and/or long‐term implant outcomes from partially edentulous patients with periodontitis who were treated and followed periodontal maintenance for ≥5 years were considered eligible for the review. Screening of the articles, data extraction, and quality assessment were conducted independently and in duplicate. Results: Search of MEDLINE, EMBASE, and CENTRAL databases resulted in 959 papers, and of them 931 were excluded after title/abstract assessment. The full texts of 28 potentially eligible publications were screened, but only 10 studies met inclusion criteria. Most of the included studies (77.8%) presented a medium/high methodologic quality. The results demonstrated that patients with a diagnosis of periodontitis had satisfactory implant outcomes. Implant survival was high (92.1%) within studies reporting 10 years of follow‐up. Parameters related to probing depth, clinical attachment level, and bone loss around teeth increased the occurrence of peri‐implantitis and implant loss. Non‐attendance to periodontal maintenance and smoking habits were also associated with less favorable implant outcomes. Conclusions: This systematic review confirmed that implant therapy can be successfully used in patients with a diagnosis of periodontitis who underwent proper therapy and regular periodontal maintenance. Residual pockets, non‐attendance to the periodontal maintenance program, and smoking were considered to be negative factors for the long‐term implant outcomes.     

Platelet-derived growth factor-B gene delivery sustains gingival fibroblast signal transduction

Background and Objective: Platelet‐derived growth factor‐BB is a potent mediator of tooth‐supporting periodontal tissue repair and regeneration. A limitation of the effects of topical platelet‐derived growth factor‐BB application is its short half‐life in vivo. Gene therapy has shown strong promise for the long‐term delivery of platelet‐derived growth factor in both skin ulcer healing and periodontal tissue engineering. However, little is known regarding the extended effects of platelet‐derived growth factor‐B on cell signaling via gene delivery, especially at the level of phosphorylation of intracellular kinases. This study sought to evaluate the effect of gene transfer by Ad‐PDGF‐B on human gingival fibroblasts (HGFs) and the subsequent regulation of genes and cell‐surface proteins associated with cellular signaling. Material and Methods: HGFs from human subjects were treated by adenoviral PDGF‐B, PDGF‐1308 (a dominant negative mutant of PDGF) and recombinant human platelet‐derived growth factor‐BB, and then incubated in serum‐free conditions for various time points and harvested at 1, 6, 12, 24, 48, 72 and 96 h. Exogenous PDGF‐B was measured by RT‐PCR and Western blot. Cell proliferation was evaluated by [methyl‐³H]thymidine incorporation assay. We used proteomic arrays to explore phosphorylation patterns of 23 different intracellular kinases after PDGF‐B gene transfer. The expression of α and β PDGFR and Akt were measured by Western blot analysis. Results: Sustained in vitro expression of PDGF‐B in HGFs by Ad‐PDGF‐B transduction was seen at both the mRNA and protein levels. Compared to rhPDGF‐BB and Ad‐PDGF‐1308, Ad‐PDGF‐B maintained cell growth in serum‐free conditions, with robust increases in DNA synthesis. Gene delivery of PDGF‐B also prolonged downregulation of the growth arrest specific gene (gas) PDGFαR. Of the 23 intracellular kinases that we tested in proteomic arrays, Akt revealed the most notable long‐term cell signaling effect as a result of the over‐expression of Ad‐PDGF‐B, compared with pulse recombinant human platelet‐derived growth factor BB. Prolonged Akt phosphorylation was induced by treatment with Ad‐PDGF‐B, for at least up to 96 h. Conclusion: These findings further demonstrate that gene delivery of PDGF‐B displays sustained signal transduction effects in human gingival fibroblasts that are higher than those conveyed by treatment with recombinant human platelet‐derived growth factor‐BB protein. These data on platelet‐derived growth factor gene delivery contribute to an improved understanding of these pathways that are likely to play a role in the control of clinical outcomes of periodontal regenerative therapy.     

Experimental and clinical studies on regenerative periodontal therapy

The recognition of a periodontal therapy as a regenerative procedure requires the demonstration of new cementum, periodontal ligament, and bone coronal to the base of the defect. A diversity of regenerative strategies has been evaluated, including root surface conditioning, bone grafts and bone substitute materials, guided tissue regeneration, enamel matrix proteins, growth/differentiation factors, combined therapies and, more recently, tissue‐engineering approaches. The aim of this chapter of Periodontology 2000 is to review the research carried out in Latin America in the field of periodontal regeneration, focusing mainly on studies using preclinical models (animal models) and randomized controlled clinical trials. This review may help clinicians and researchers to evaluate the current status of the therapies available and to discuss the challenges that must be faced in order to achieve predictable periodontal regeneration in clinical practice.     

Allogeneic Stem Cells From Deciduous Teeth in Treatment for Periodontitis in Miniature Swine

Background: Regeneration of lost periodontium in periodontitis is a challenge in that alveolar bone, cementum, and periodontal ligament need to be restored to their original architecture. Stem cells from exfoliated deciduous teeth (SHEDs) appear to be an attractive candidate for periodontium tissue regeneration. Previously, the authors successfully regenerated periodontal defects using autologous and allogeneic periodontal ligament stem cells (PDLSCs). The purpose of the present study is to investigate the ability of allogeneic SHEDs to regenerate lost periodontium in a swine periodontitis model. Methods: Animal models of periodontitis were established in miniature pigs, and allogeneic stem cells were isolated from miniature pig deciduous teeth (SPDs). The animal models were treated with SPDs plus hydroxyapatite/tricalcium phosphate (HA/TCP). Allogeneic PDLSCs plus HA/TCP or HA/TCP alone were set as positive control or control, respectively. Clinical assessments, computed tomography (CT) scanning, and histologic examination were used to evaluate the outcome of tissue regeneration. Results: Clinical indices including probing depth, gingival recession, and attachment loss showed significant restoration in the SPD and PDLSC treatment groups, compared to the HA/TCP group 12 weeks post‐transplantation. Meanwhile, CT scans showed that 75% of the samples had successful hard‐tissue regeneration in both PDLSC and SPD groups, compared to the HA/TCP group, where the success rate was only 25%. In addition, histologic examination demonstrated that SPD and PDLSC treatment brought about remarkable regeneration of periodontal tissues, whereas periodontal regeneration was rare in the HA/TCP group. Conclusions: Allogeneic SPDs can effectively repair hard and soft tissue loss brought about by periodontitis in a swine model. Allogeneic SHEDs, which are easily accessible, may be applied to treat periodontitis in clinics in the future.     

Effect of platelet-rich plasma on bone regeneration in dentistry: a systematic review

Objective: To review systematically the reported effects of platelet‐rich plasma (PRP) on bone regeneration. Material and methods: Up to June 2006, MEDLINE and Cochrane databases were explored with different combinations of three search terms: ‘PRP’, ‘bone regeneration’, ‘dentistry’ and their synonyms. Inclusion criteria: human controlled clinical trials designed to treat maxillofacial bony defects with application of PRP (test) or without PRP (control), including at least five patients with a follow‐up period of more than 3 months and using clinical assessment, radiography, histology and/or histomorphometry for evaluation. Literature search, selection of eligible articles and data extraction were carried out independently by two readers. Results: The literature search revealed 108 references, of which 17 were selected for further analysis. Finally, nine articles fulfilling the inclusion criteria were selected for systematically review. Owing the substantial heterogeneity of the studies it was not possible to analyze the data statistically. An attempt was made to compare results from studies that used similar outcome measures by calculating and adding confidence intervals to the data presented in the original papers. Differences in treatment effects for periodontal defects in terms of clinical attachment level (CAL) were significant (ranging from 0.8 to 3.2 mm). The reported effects of PRP in sinus elevation (compared with their controls) were <10%. Conclusion: We found evidence for beneficial effects of PRP in the treatment of periodontal defects. Evidence for beneficial effects of PRP in sinus elevation appeared to be weak. No conclusions can be drawn about other applications of PRP in dentistry.     

A prospective,randomized pilot study on the safety and efficacy of recombinant human growth and differentiation factor‐5 coated onto β‐tricalcium phosphate for sinus lift augmentation

Objectives: The aim of this prospective, randomized clinical trial was to investigate the potential of recombinant human growth and differentiation factor‐5 (rhGDF‐5) coated onto β‐tricalcium phosphate (β‐TCP) (rhGDF‐5/β‐TCP) to support bone formation after sinus lift augmentation. Material and methods: In total, 31 patients participated in this multicenter clinical trial. They required a two‐stage unilateral maxillary sinus floor augmentation (residual bone height <5 mm). According to a parallel‐group design, the patients were randomized to three treatment groups: (a) augmentation with rhGDF‐5/β‐TCP and a 3‐month healing period, (b) augmentation with rhGDF‐5/β‐TCP and a 4‐month healing period and (c) medical device β‐TCP mixed with autologous bone and a 4‐month healing period. The primary study objective was the area of newly formed bone within the augmented area as assessed by histomorphometric evaluation of trephine bur biopsies. Results: The osseous regeneration was similar in each treatment group; the amount of newly formed bone ranged between 28% (± 15.5%) and 31.8% (± 17.9%). Detailed analysis of histological data will be published elsewhere. As secondary efficacy variables, the augmentation height at the surgery site was measured by radiography. The largest augmentation was radiologically achieved in the rhGDF‐5/β‐TCP – 3‐month and the rhGDF‐5/β‐TCP – 4‐month treatment groups. As safety parameters, adverse events were recorded and anti‐drug antibody levels were evaluated. Most of the adverse events were judged as unrelated to the study medication. Four out of 47 (8.5%) implants failed in patients treated with rhGDF‐5/β‐TCP, a result that is in agreement with the general implant failure rate of 5–15%. Transiently very low amounts of anti‐rhGDF‐5 antibodies were detected in some patients who received rhGDF‐5, which was not related to the bone formation outcome. Conclusion: rhGDF‐5/β‐TCP was found to be effective and safe as the control treatment with autologous bone mixed β‐TCP in sinus floor augmentation. Thus, further investigation regarding efficacy and safety will be carried out in larger patient populations. To cite this article:
Koch FP, Becker J, Terheyden H, Capsius B, Wagner W, on behalf of the research group of this multicenter clinical trial. A prospective, randomized pilot study on the safety and efficacy of recombinant human growth and differentiation factor‐5 coated onto β‐tricalcium phosphate for sinus lift augmentation.
Clin. Oral Impl. Res. 21 , 2010; 1301–1308.
doi: 10.1111/j.1600‐0501.2010.01949.x     

Periodontal regeneration in humans using recombinant human platelet-derived growth factor-BB (rhPDGF-BB) and allogenic bone

BACKGROUND: Purified recombinant human platelet-derived growth factor BB (rhPDGF-BB) is a potent wound healing growth factor and stimulator of the proliferation and recruitment of both periodontal ligament (PDL) and bone cells. The hypothesis tested in this study was that application of rhPDGF-BB incorporated in bone allograft would induce regeneration of a complete new attachment apparatus, including bone, periodontal ligament, and cementum in human interproximal intrabony defects and molar Class II furcation lesions. METHODS: Nine adult patients (15 sites) with advanced periodontitis exhibiting at least one tooth requiring extraction due to an extensive interproximal intrabony and/or molar Class II furcation defect were entered into the study. Eleven defects were randomly selected to receive rhPDGF-BB. Following full-thickness flap reflection and initial debridement, the tooth roots were notched at the apical extent of the calculus, the osseous defects were thoroughly debrided, and the tooth root(s) were planed/prepared. The osseous defects were then filled with demineralized freeze-dried bone allograft (DFDBA) saturated with one of three concentrations of rhPDGF-BB (0.5 mg/ml, 1.0 mg/ml, or 5.0 mg/ml). Concurrently, four interproximal defects were treated with a well accepted commercially available graft (anorganic bovine bone in collagen, ABB-C) and a bilayer collagen membrane. Radiographs, clinical probing depths, and attachment levels were obtained preoperatively (at baseline) and 9 months later. At 9 months postoperatively, the study tooth and surrounding tissues were removed en bloc. Clinical and radiographic data were analyzed for change from baseline by defect type and PDGF concentration. The histologic specimens were analyzed for the presence of regeneration of a complete new attachment apparatus coronal to the reference notch. RESULTS: The post-surgical wound rapidly healed and was characterized by firm, pink gingivae within 7 to 10 days of surgery. There were no unfavorable tissue reactions or other safety concerns associated with the treatments throughout the course of the study. In rhPDGF/allograft sites, the vertical probing depth (vPD) reduction for interproximal defects was 6.42 +/- 1.69 mm (mean +/- SD) and clinical attachment level (CAL) gain was 6.17 +/- 1.94 mm (both P < 0.01). Radiographic fill was 2.14 +/- 0.85 mm. Sites filled with ABB-C had a PD reduction and CAL gain of 5.75 +/- 0.5 and 5.25 +/- 1.71, respectively. Furcation defects treated with rhPDGF/allograft exhibited a mean horizontal and vertical PD reduction of 3.40 +/- 0.55 mm (P < 0.001) and 4.00 +/- 1.58 mm (P < 0.005), respectively. The CAL gain for furcation defects was 3.2 +/- 2.17 mm (P < 0.030). Histologic evaluation revealed regeneration of a complete periodontal attachment apparatus, including new cementum, PDL, and bone coronal to the root notch in four of the six interproximal defects and all evaluable (four of four) furcation defects treated with PDGF. Two of the four interproximal intrabony defects treated with ABB-C and membrane exhibited regeneration. CONCLUSIONS: Use of purified rhPDGF-BB mixed with bone allograft results in robust periodontal regeneration in both Class II furcations and interproximal intrabony defects. This is the first report of periodontal regeneration demonstrated histologically in human Class II furcation defects.