Platelet-derived growth factor stimulates bone fill and rate of attachment level gain: results of a large multicenter randomized controlled trial

BACKGROUND: Growth factors are generally accepted to be essential mediators of tissue repair via well-established mechanisms of action that include stimulatory effects on angiogenesis and cellular proliferation, ingrowth, differentiation, and matrix biosynthesis. The aim of this study was to evaluate in a large-scale, prospective, blinded, and randomized controlled clinical trial the safety and effectiveness of purified recombinant human platelet-derived growth factor (rhPDGF-BB) mixed with a synthetic beta-tricalcium phosphate (beta-TCP) matrix for the treatment of advanced periodontal osseous defects at 6 months of healing. METHODS: Eleven clinical centers enrolled 180 subjects, each requiring surgical treatment of a 4 mm or greater intrabony periodontal defect and meeting all inclusion and exclusion criteria. Subjects were randomized into one of three treatment groups: 1) beta-TCP + 0.3 mg/ml rhPDGF-BB in buffer; 2) beta-TCP + 1.0 mg/ml rhPDGF-BB in buffer; and 3) beta-TCP + buffer (active control). Safety data were assessed by the frequency and severity of adverse events. Effectiveness measurements included clinical attachment levels (CAL) and gingival recession (GR) measured clinically and linear bone growth (LBG) and percent bone fill (% BF) as assessed radiographically by an independent centralized radiology review center. The area under the curve (AUC), an assessment of the rate of healing, was also calculated for CAL measurements. The surgeons, clinical and radiographic evaluators, patients, and study sponsor were all masked with respect to treatment groups. RESULTS: CAL gain was significantly greater at 3 months for group 1 (rhPDGF 0.3 mg/ml) compared to group 3 (beta-TCP + buffer) (3.8 versus 3.3 mm; P = 0.032), although by 6 months, this finding was not statistically significant (P = 0.11). This early acceleration of CAL gain led to group 1 exhibiting a significantly greater rate of CAL gain between baseline and 6 months than group 3 as assessed by the AUC (68.4- versus 60.1-mm weeks; P = 0.033). rhPDGF (0.3 mg/ml)-treated sites also had significantly greater linear bone gain (2.6 versus 0.9 mm, respectively; P < 0.001) and percent defect fill (57% versus 18%, respectively; P < 0.001) than the sites receiving the bone substitute with buffer at 6 months. There was less GR at 3 months in group 1 compared to group 3 (P = 0.04); at 6 months, GR for group 1 remained unchanged, whereas there was a slight gain in gingival height for group 3 resulting in comparable GR. There were no serious adverse events attributable to any of the treatments. CONCLUSIONS: To our knowledge, this study is the largest prospective, randomized, triple-blinded, and controlled pivotal clinical trial reported to date assessing a putative periodontal regenerative and wound healing therapy. The study demonstrated that the use of rhPDGF-BB was safe and effective in the treatment of periodontal osseous defects. Treatment with rhPDGF-BB stimulated a significant increase in the rate of CAL gain, reduced gingival recession at 3 months post-surgery, and improved bone fill as compared to a beta-TCP bone substitute at 6 months.     

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.     

Effect of rhPDGF-BB on bone turnover during periodontal repair

PURPOSE: Growth factors such as platelet-derived growth factor (PDGF) exert potent effects on wound healing including the regeneration of periodontia. Pyridinoline cross-linked carboxyterminal telopeptide of type I collagen (ICTP) is a well-known biomarker of bone turnover, and as such is a potential indicator of osseous metabolic activity. The objective of this study was to evaluate the release of the ICTP into the periodontal wound fluid (WF) following periodontal reconstructive surgery using local delivery of highly purified recombinant human PDGF (rhPDGF)-BB. METHODS: Forty-seven human subjects at five treatment centres possessing chronic severe periodontal disease were monitored longitudinally for 24 weeks following PDGF regenerative surgical treatment. Severe periodontal osseous defects were divided into one of three groups and treated at the time of surgery with either: beta-tricalcium phosphate (TCP) osteoconductive scaffold alone (active control), beta-TCP+0.3 mg/ml of rhPDGF-BB, or beta-TCP+1.0 mg/ml of rhPDGF-BB. WF was harvested and analysed for local ICTP levels by radioimmunoassay. Statistical analysis was performed using analysis of variance and an area under the curve analysis (AUC). RESULTS: The 0.3 and 1.0 mg/ml PDGF-BB treatment groups demonstrated increases in the amount of ICTP released locally for up to 6 weeks. There were statistically significant differences at the week 6 time point between beta-TCP carrier alone group versus 0.3 mg/ml PDGF-BB group (p<0.05) and between beta-TCP alone versus the 1.0 mg/ml PDGF-BB-treated lesions (p<0.03). The AUC analysis revealed no statistical differences amongst groups. CONCLUSION: This study corroborates the release of ICTP as a measure of active bone turnover following local delivery of PDGF-BB to periodontal osseous defects. The amount of ICTP released from the WF revealed an early increase for all treatment groups. Data from this study suggests that when PDGF-BB is delivered to promote periodontal tissue engineering of tooth-supporting osseous defects, there is a direct effect on ICTP released from the wound.     

Clinical and Radiographic Evaluation of Demineralized Freeze‐Dried Bone Allograft Versus Platelet‐Rich Fibrin for the Treatment of Periodontal Intrabony Defects in Humans

Background: A wide variety of materials have been proposed for treatment of periodontal intrabony defects (IBDs); recently, platelet‐rich fibrin (PRF) has been suggested as a grafting material. The aim of this study is to report changes in clinical attachment level (CAL) and bone fill of periodontal IBDs treated with demineralized freeze‐dried bone allograft (DFDBA) compared with PRF in humans. Methods: Thirty‐six patients completed the study protocol. Each patient contributed a single IBD, which was randomized to receive either DFDBA or PRF. Clinical and standardized radiographic data were collected at baseline and 6 months after treatment. Primary outcome measures included: 1) radiographic bone fill as measured from the cemento‐enamel junction to base of bony defect and 2) change in CAL. Results: Both treatment groups had significant gains in CAL as well as bone fill, with no significant differences in outcomes between groups. DFDBA had a mean CAL gain of 1.16 ± 1.33 mm, mean clinical bone fill of 1.53 ± 1.64 mm, and mean radiographic bone fill of 1.14 ± 0.88 mm. PRF had a mean CAL gain of 1.03 ± 0.86 mm, mean clinical bone fill of 1.35 ± 1.60 mm, and mean radiographic bone fill of 1.10 ± 1.01 mm. Conclusion: Treatment of IBDs with either DFDBA or PRF resulted in a significant gain in CAL as well as bone fill after 6 months of healing, with no significant difference between materials.     

New composite endpoints to assess efficacy in periodontal therapy clinical trials

BACKGROUND: Clinical attachment level (CAL) and bone height (radiographic or clinical) are two well-accepted endpoint measures for periodontal clinical trials; however, neither one has been shown to be more predictive of long-term success than the other. We propose using a composite endpoint analysis combining clinical and radiological parameters to assess the beneficial effects on both hard and soft tissues following periodontal therapy using a single statistical test. To address this need, two composite endpoint alternatives are offered as a yardstick for clinical success; each includes the improvement in CAL and either improvement in linear bone growth or percent bone fill. METHODS: The data for composite endpoint analyses were derived from a clinical trial evaluating two concentrations of recombinant human platelet-derived growth factor-BB (rhPDGF-BB) with beta-tricalcium phosphate (beta-TCP) compared to beta-TCP plus buffer as follows: group I, beta-TCP + 0.3 mg/ml rhPDGF-BB; group II, beta-TCP + 1.0 mg/ml rhPDGF-BB; and group III, beta-TCP + buffer. The construction of composite endpoints was based on the greatest values for change, accepted by the U.S. Food and Drug Administration (FDA), for clinical attachment level (DeltaCAL), mean change in radiographic linear bone gain (LBG), and mean radiographic percent bone fill (%BF), with the following dual standards defining a successful clinical result: CAL gain > or =2.67 mm and radiographic LBG > or =1.1 mm at 6 months and CAL gain > or =2.67 mm and radiographic %BF > or =14.1% at 6 months. RESULTS: Group I (beta-TCP + 0.3 mg/ml rhPDGF-BB) demonstrated statistically significant differences from group III (active control) for both composite endpoints. For the CAL/LBG composite endpoint, 61.7% of sites in group I versus 30.4% of sites in group III met the composite endpoint benchmarks (P <0.001). For the CAL/%BF composite endpoint, 70% of sites in group I versus 44.6% of sites in group III met the composite endpoint benchmarks (P = 0.003). A non-significant trend was observed for group II versus group III with 37.9% (P = 0.20) and 55.2% (P = 0.13) of sites meeting the CAL/LBG and CAL/%BF composite endpoints, respectively. These results are further emphasized by findings demonstrating a low correlation between the individual efficacy endpoints (DeltaCAL and %BF; DeltaCAL and LBG) for each of the three treatment groups. CONCLUSIONS: Composite endpoints are advantageous in periodontal clinical trials where no single efficacy endpoint has been established as the most important. A composite endpoint, combining outcome measures of both hard and soft tissue components of the periodontium, may be preferable for assessing efficacy of periodontal regenerative therapies. Two composite endpoints are offered to meet this need.     

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.     

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.     

Intrabony Defects,Open‐Flap Debridement,and Decortication: A Randomized Clinical Trial

Background: Intramarrow penetration (IMP) is often incorporated in regenerative periodontal surgical procedures. However, the actual benefits of adding IMP to such a procedure remain undocumented. The purpose of this randomized controlled trial was to investigate the contribution of IMP to the outcomes of open‐flap debridement (OFD) treatment of intrabony defects. Methods: Forty‐two chronic periodontitis patients, each contributing a 2‐wall, 3‐wall, or combined 2‐ to 3‐wall intrabony defect, were treated. Sites were randomly assigned into one of two groups: control (OFD alone) or test (OFD + IMP). Papilla preservation flaps were raised, and defects were thoroughly debrided. In the control group, complete primary closure of flaps was ensured after debridement. In the test group, IMP was performed before flap closure, using a round bur to penetrate the cortical defect wall. Clinical and radiographic parameters were assessed at baseline and 12 months after treatment. Results: At baseline, there were no statistically significant differences between groups. At 12 months, both groups experienced significant improvements, in terms of probing depth reduction, clinical attachment level (CAL) gain, and bone level (clinical and radiographic). The test group experienced significantly greater clinical bone gain (3.07 ± 1.74 mm) and prevalence of CAL gain ≥2 mm (93% of sites) compared with the control group (1.76 ± 2.71 mm, P <0.03; 62%, P = 0.024). The test treatment benefits were particularly evident in mandibular sites, in which OFD + IMP doubled the radiographic bone gain obtained by OFD alone. Conclusion: Addition of IMP to an OFD procedure used to treat intrabony defects results in statistically and clinically significant enhancement of both clinical and radiographic outcomes.     

Crevicular Fluid Growth Factors Release Profile Following the Use of Platelet‐Rich Fibrin and Plasma Rich Growth Factors in Treating Periodontal Intrabony Defects: A Randomized Clinical Trial

Background: The open, usually contaminated nature of periodontal defects could negatively affect availability and activity of platelet concentrate–suggested growth factors (GF). The aim of this study is to test this hypothesis and investigate concentrations of: 1) vascular endothelial growth factor (VEGF) and 2) platelet‐derived growth factor (PDGF‐BB) in gingival crevicular fluid (GCF) from localized intrabony defects treated with platelets rich in growth factors (PRGF) or platelet‐rich fibrin (PRF) compared with a control xenograft defect filling. Methods: Thirty non‐smoking patients suffering severe chronic periodontitis were allocated to this randomized, prospective, single‐masked trial. Each patient had one interproximal defect randomly distributed to: 1) group 1: bone‐substitute grafting control (n = 10); 2) group 2: experimental PRGF (n = 10); or 3) group 3: PRF (n = 10). Clinical parameters were measured at baseline and 6 and 9 months following therapy. GCF samples were obtained on days 1, 3, 7, 14, 21, and 30 after therapy for evaluation of VEGF and PDGF‐BB levels. Results: On days 1, 3, and 7 following surgery, mean levels of VEGF and PDGF‐BB at sites treated with PRGF and PRF were not significantly different versus the control. Levels of PDGF‐BB and VEGF were higher in the PRGF‐treated group, but differences were not significant. Growth factor levels decreased significantly in samples collected on days 14, 21, and 30 with non‐significant differences among the three groups. No significant clinical differences were reported among the three groups during the two observation periods (early period: days 1, 3, and 7; and later period: days 14, 21, and 30). Conclusions: Within the limits of the present study, it can be concluded that PRF and PRGF platelet concentrate failed to augment clinical effects achieved with the xenograft alone in treating intrabony defects. Periodontal defects could not retain extraphysiologic levels of GF suggested to be associated with platelet concentrate.     

Platelet‐Derived Growth Factor‐BB Release Profile in Gingival Crevicular Fluid After Use of Marginal Periosteal Pedicle Graft as an Autogenous Guided Tissue Membrane to Treat Localized Intrabony Defects

Background: The aim of this study is to evaluate levels of platelet‐derived growth factor‐BB (PDGF‐BB) in gingival crevicular fluid (GCF) during the early stages of healing for sites treated by marginal periosteal pedicle (MPP) graft as an autogenous guided tissue membrane compared to that of the control open flap debridement (OFD). Methods: Fifteen non‐smoking patients (13 males and 2 females) with severe chronic periodontitis participated in this prospective, controlled, masked trial. Each subject contributed matched pairs of 2‐ or 3‐walled intrabony interproximal defects in premolar or molar teeth. Interproximal contralateral defects were randomly assigned to either the MPP group 1 or control OFD group 2. GCF samples were collected at 1, 3, 7, 14, and 30 days after surgery. PDGF‐BB in the GCF samples was measured using a human PDGF‐BB enzyme‐linked immunosorbent assay kit. Results: In both MPP and OFD, PDGF‐BB concentrations peaked in the samples obtained during the early postoperative days (days 2 and 3) and decreased sharply in the samples obtained 7, 14, and 30 days post‐surgery. Conclusion: Periosteal coverage of periodontal defects is not associated with a significant increase in PDGF‐BB levels.     

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.     

Comparative Evaluation of Autologous Platelet‐Rich Fibrin and Platelet‐Rich Plasma in the Treatment of 3‐Wall Intrabony Defects in Chronic Periodontitis: A Randomized Controlled Clinical Trial

Background: The topical use of platelet concentrates is recent, and its efficiency remains controversial. The present study aims to explore the clinical and radiographic effectiveness of autologous platelet‐rich fibrin (PRF) and platelet‐rich plasma (PRP) in the treatment of intrabony defects in patients with chronic periodontitis. Methods: Ninety intrabony defects were treated with either autologous PRF with open‐flap debridement or autologous PRP with open‐flap debridement or open‐flap debridement alone. Clinical and radiologic parameters, such as probing depth (PD), clinical attachment level (CAL), intrabony defect depth, and percentage defect fill, were recorded at baseline and 9 months postoperatively. Results: Mean PD reduction and CAL gain were greater in PRF (3.77 ± 1.19 and 3.17 ± 1.29 mm) and PRP (3.77 ± 1.07 and 2.93 ± 1.08 mm) groups than the control group (2.97 ± 0.93 and 2.83 ± 0.91 mm). Furthermore, significantly greater percentage of mean bone fill was found in the PRF (55.41% ± 11.39%) and PRP (56.85% ± 14.01%) groups compared with the control (1.56% ± 15.12%) group. Conclusions: Within the limit of the present study, there was similar PD reduction, CAL gain, and bone fill at sites treated with PRF or PRP with conventional open‐flap debridement. Because PRF is less time consuming and less technique sensitive, it may seem a better treatment option than PRP. However, long‐term, multicenter randomized, controlled clinical trials will be required to know their clinical and radiographic effects on bone regeneration.     

Porous titanium granules in the treatment of mandibular Class II furcation defects: a consecutive case series

Background: The osteoconductive potential of titanium is interesting from the perspective of periodontal surgery and reconstitution of osseous defects. The aim of the present consecutive case series is to evaluate a surgical strategy based on the use of porous titanium granules (PTG) in the treatment of Class II buccal furcation defects in mandibular molars in humans. Methods: Surgical intervention with PTG used as a bone graft substitute was performed in 10 patients with 10 mandibular Class II buccal furcation defects. Clinical parameters (probing depth (PD), clinical attachment level (CAL), gingival recession (GR), gingival index (GI), bleeding on probing (BOP), and horizontal and vertical bone sounding) and radiographic measurements of vertical furcation height were compared among baseline (presurgery), 6, and 12 months (post‐surgery). The significance level (α) was set at 0.05. Results: With respect to vertical and horizontal bone sounding measurements, CAL, and GR, no significant improvements between baseline and the 12‐month examination were seen. Both PD and radiographic vertical furcation height were significantly reduced between baseline and 12 months. When comparing the baseline to 12‐month data, a significantly lower GI score was seen but the BOP score was unchanged. None of the treated teeth showed radiographic signs of root resorption. Conclusion: This study suggests that PTG is safe to use in close proximity to root surfaces, but no significant improvements in clinical endpoints of defect resolution were observed.     

Enamel Matrix Derivative,Alone or Associated With a Synthetic Bone Substitute,in the Treatment of 1‐ to 2‐Wall Periodontal Defects

Background: In this study, we compare the effects of enamel matrix derivative (EMD) associated with a hydroxyapatite and β‐tricalcium phosphate (HA/β‐TCP) implant to EMD alone and to open‐flap debridement (OFD) when surgically treating 1‐ to 2‐wall intrabony defects. Methods: Thirty‐four patients, exhibiting ≥3 intraosseous defects in different quadrants, were each treated by OFD, EMD, or EMD + HA/β‐TCP in each defect. At baseline and 12 and 24 months, a complete clinical and radiographic examination was done. Pre‐therapy and post‐therapy clinical (probing depth [PD], clinical attachment level [CAL], and gingival recession [GR]) and radiographic (defect bone level [DBL] and radiographic bone gain [RBG]) parameters for the different treatments were compared. Results: After 12 and 24 months, almost all the clinical and radiographic parameters showed significant changes from baseline within each group (P <0.001). Differences in PD, CAL, and DBL scores were also seen among the three groups at the 12‐ and 24‐month visits (P <0.001). At 12 and 24 months after treatment, the EMD + HA/β‐TCP group showed significantly greater PD reduction (4.00 ± 0.42 mm; 4.25 ± 0.63 mm), CAL gain (3.47 ± 0.65 mm; 3.63 ± 0.91 mm), and RBG (3.17 ± 0.69 mm; 3.35 ± 0.80 mm) and less GR increase (0.56 ± 0.37 mm; 0.63 ± 0.42 mm) compared with the OFD and EMD groups (P <0.05). Conclusion: Our data support the hypothesis that the adjunct of an HA/β‐TCP composite implant with EMD may improve the clinical and radiographic outcomes of the surgical treatment of unfavorable intrabony defects.     

Long‐Term Effect of Four Surgical Periodontal Therapies and One Non‐Surgical Therapy: A Systematic Review and Meta‐Analysis

Background: The aim of this systematic review is to evaluate the long term (≥2 years) effect of four surgical and non‐surgical therapies in treating periodontal disease. Methods: An electronic search of four databases and a hand search of peer‐reviewed journals for relevant articles were conducted. Prospective human controlled clinical trials were included that compared surgical therapy to non‐surgical therapy in ≥10 patients diagnosed with chronic periodontitis with a follow‐up period of ≥2 years and that reported change in probing depth (PD) and clinical attachment level (CAL) after the therapy. Random effect meta‐analysis was performed to compare the outcome of surgical and non‐surgical therapy in shallow, moderate, and deep PD. Results: Eight human prospective clinical trials were included. In 1‐ to 3‐mm PD, scaling and root planing (SRP), modified Widman flap (MWF), and osseous surgery (OS) resulted in 23.2%, 39.4%, and 61.39% CAL loss, respectively; SRP, MWF, and OS resulted in increased mean PD of 2.5%, 3.3%, and 6.3%, respectively. In 4‐ to 6‐mm PD, SRP, MWF, and OS resulted in 8.4%, 6.5%, and 5.22% CAL gain, respectively; SRP, MWF, and OS resulted in 18.7%, 25.4%, and 30.8% PD reduction, respectively. In PD ≥7 mm, SRP, MWF, and OS resulted in 9.8%, 14.2%, and 9.38% CAL gain, respectively; SRP, MWF, and OS resulted in mean PD reduction of 21.6%, 33.1%, and 42.8%, respectively. Conclusions: Surgical therapy had significantly more CAL loss than non‐surgical therapy in shallow PD. In moderate PD, MWF had significantly more PD reduction than SRP, and there was significantly less CAL gain with surgical therapy. In deep PD, OS had significantly higher PD reduction than SRP.     

Role of Space Provision in Regeneration of Localized Two‐Wall Intrabony Defects Using Periosteal Pedicle Graft as an Autogenous Guided Tissue Membrane

Background: Marginal pedicle periosteum (MPP) has been used as a rigid membrane in guided tissue regeneration (GTR) for osseous defects. The present study aims to study the effect of space provision by an alloplastic graft material in bone defect area (BDA) reduction of 2‐wall defects. Methods: Twenty interproximal intrabony 2‐wall defects in healthy non‐smoking patients with chronic periodontitis were randomly divided in control (group 1, periosteum alone) and experimental (group 2, periosteum with alloplastic graft material) groups. Measurements of probing depth (PD), clinical attachment level (CAL), and radiographic BDA were done at the baseline and 6‐month postoperative evaluations. Results: The 6‐month postoperative assessment showed clinical and radiographic improvements with PD reduction, CAL gain, and changes in BDA in both groups, which was statistically significant compared with baseline (P <0.05). However, BDA reduction was statistically greater in group 2 (48.88% ± 18.61%) compared with group 1 (14.08% ± 12.97%) at the 6‐month follow‐up (P = 0.009). Conclusion: Within the limitations of this study, it can be concluded that space provision by an alloplastic graft material increases the regenerative potential of MPP as a GTR membrane and results in increased defect fill.     

Platelet‐Rich Fibrin Combined With a Porous Hydroxyapatite Graft for the Treatment of 3‐Wall Intrabony Defects in Chronic Periodontitis: A Randomized Controlled Clinical Trial

Background: Porous hydroxyapatite (HA) bone grafting material has been used to fill periodontal intrabony defects (IBDs), resulting in clinically acceptable responses. Platelet‐rich fibrin (PRF) is a leukocyte and platelet preparation that concentrates various polypeptide growth factors and, therefore, has the potential for use as regenerative treatment for periodontal defects. The present study aims to explore the clinical and radiographic effectiveness of autologous PRF versus PRF + HA in treatment of IBDs in patients with chronic periodontitis. Methods: Ninety IBDs were treated with autologous PRF with open‐flap debridement (OFD), PRF + HA with OFD, or OFD (controls) alone. Clinical and radiologic parameters, including probing depth (PD), clinical attachment level (CAL), IBD depth, and percentage defect fill were recorded at baseline and 9 months postoperatively. Results: Mean PD reduction was greater in PRF (3.90 ± 1.09 mm) and PRF + HA (4.27 ± 0.98 mm) groups than the control group (2.97 ± 0.93 mm), and mean CAL gain was greater in PRF (3.03 ± 1.16 mm) and PRF + HA (3.67 ± 1.03 mm) compared to controls (2.67 ± 1.09 mm). Furthermore, significantly greater percentage of mean bone fill was found in the PRF (56.46% ± 9.26%) and PRF + HA (63.39% ± 16.52%) groups compared to controls (15.96% ± 13.91%). Conclusions: Treatment of IBD with PRF results in significant improvements of clinical parameters compared to baseline. When added to PRF, HA increases the regenerative effects observed with PRF in the treatment of 3‐wall IBDs.     

Subperiosteal connective tissue grafts for pocket reduction and preservation of gingival esthetics: a case report

BACKGROUND: Clinical studies and recent histological evidence following mucogingival surgery for the treatment of gingival recession have documented that when closely adapted to a previously exposed root surface, connective tissue is capable of forming a new attachment. Despite these findings, no clinical tests have been conducted to examine the ability of connective tissue to reduce probing depth (PD) and increase clinical attachment levels (CAL) when it is implanted into periodontal osseous defects. The purpose of this paper is to report the clinical results on a patient following 2 subperiosteal connective tissue grafts. METHODS: Subperiosteal connective tissue grafts were placed in 2 sites of periodontal bone loss and deep pocketing in one patient. Following flap reflection and root preparation, a connective tissue graft 1.5 to 2.0 mm in thickness was draped and sutured over each osseous defect and then completely covered by the external flap. RESULTS: Ten months following subperiosteal connective tissue grafting, tooth #7 had 4 mm of CAL gain. Tooth #10 had 3 mm of CAL gain 8 months postoperatively. Both teeth had 1 mm gain in gingival recession. Both teeth probed 3 mm postoperatively. CONCLUSIONS: When connective tissue was grafted into 2 periodontal osseous defects, there were significant reductions in probing depth and gains in CAL. There was minimal postoperative gingival recession. The new clinical attachment gain remained stable for 8 to 10 months following subperiosteal connective tissue grafting.     

Polymer-assisted regeneration therapy with Atrisorb barriers in human periodontal intrabony defects

AIM: This study compared clinical results of 40 periodontal osseous defects treated by two types of absorbable barrier materials. MATERIAL AND METHODS: Thirty patients (23 males and seven females) suffering from moderate to advanced periodontitis (with comparable osseous defects) were randomly assigned to receive either Atrisorb barrier (n = 22; group A) or Resolut XT barrier (n = 18; group B) therapy. Periodontal phase I treatment and oral hygiene instruction were performed before periodontal surgery. Papillary preservation, partial thickness flap, citric acid root conditioning, and decortication procedures were applied during the operation. Bone defects were filled with demineralized freeze-dried bone allograft and minocycline mixture (4:1 ratio). Postoperative care included 0.10% chlorhexidine rinse daily and antibiotic medication for 2 weeks. Clinical assessments including probing depth (PD), clinical attachment level (CAL), gingival recession (GR), plaque index (PII), gingival index (GI), and radiographic examinations were taken at the baseline, preoperatively and at 3 and 6 months after regenerative surgery. RESULTS: Six months following therapy, both Atrisorb and Resolut XT groups had achieved comparable clinical improvement in pocket reduction (3.9 versus 4.4 mm), attachment tissue gain (clinical attachment gain; 3.5 versus 3.6 mm), and reduction in the GI and in the PII. Within-group comparisons showed significant attachment gain and pocket reduction between baseline data and those at both 3 and 6 months postoperatively (p < 0.01). There were no statistically significant differences in any measured data between groups A and B. CONCLUSIONS: The results of this study indicate that a comparable and favorable regeneration of periodontal defects can be achieved with both Atrisorb and Resolut XT barriers. Further long-term study and histologic observations of tissue healing are needed to evaluate whether Atrisorb is promising for clinical use.     

Five‐Year Results Evaluating the Effects of Platelet‐Rich Plasma on the Healing of Intrabony Defects Treated With Enamel Matrix Derivative and Natural Bone Mineral

Background: Regenerative periodontal surgery using the combination of enamel matrix derivative (EMD) and natural bone mineral (NBM) with and without addition of platelet‐rich plasma (PRP) has been shown to result in substantial clinical improvements, but the long‐term effects of this combination are unknown. Methods: The goal of this study was to evaluate the long‐term (5‐year) outcomes after regenerative surgery of deep intrabony defects with either EMD + NBM + PRP or EMD + NBM. Twenty‐four patients were included. In each patient, one intrabony defect was randomly treated with either EMD + NBM + PRP or EMD + NBM. Clinical parameters were evaluated at baseline and 1 and 5 years after treatment. The primary outcome variable was clinical attachment level (CAL). Results: The sites treated with EMD + NBM + PRP demonstrated a mean CAL change from 10.5 ± 1.6 to 6.0 ± 1.7 mm (P <0.001) at 1 year and 6.2 ± 1.5 mm (P <0.001) at 5 years. EMD + NBM–treated defects showed a mean CAL change from 10.6 ± 1.7 to 6.1 ± 1.5 mm (P <0.001) at 1 year and 6.3 ± 1.4 mm (P <0.001) at 5 years. At 1 year, a CAL gain of ≥4 mm was measured in 83% (10 of 12) of the defects treated with EMD + NBM + PRP and in 100% (all 12) of the defects treated with EMD + NBM. Compared to baseline, in both groups at 5 years, a CAL gain of ≥4 mm was measured in 75% (nine of 12 in each group) of the defects. Four sites in the EMD + PRP + NBM group lost 1 mm of the CAL gained at 1 year. In the EMD + NBM group, one defect lost 2 mm and four other defects lost 1 mm of the CAL gained at 1 year. No statistically significant differences in any of the investigated parameters were observed between the two groups. Conclusions: Within their limits, the present results indicate that: 1) the clinical outcomes obtained with both treatments can be maintained up to a period of 5 years; and 2) the use of PRP does not appear to improve the results obtained with EMD + NBM.