Recombinant Human Platelet-derived Growth factor-BB Research Articles

Recombinant Platelet-Derived Growth Factor-BB (rhPDGF-BB) Augmented Collagen Grafting for Oral Mucosal Defect Reconstruction

Abstract Objective To assess the suitability of collagen grafting and compare the outcomes between rhPDGF-BB (recombinant human platelet-derived growth factor-BB) augmented collagen grafting and collagen alone grafting for oral mucosal defect reconstruction. Method A total of 30 patients, who were planned for surgical excision of various intraoral lesions, participated in the study. These participants were then randomly assigned into two groups. Group I underwent reconstruction with collagen sheet with rhPDGF-BB, while group II underwent reconstruction with collagen sheet alone. Post-operatively, haemostasis, pain, granulation, epithelialisation and healing contracture were assessed. Results The lesions that were treated included leucoplakia, erythroplakia, oral submucous fibrosis and verrucous carcinoma. Use of collagen was associated with good haemostasis, pain relief, granulation tissue formation and epithelialisation. Group I was found to develop slightly better granulation tissue, epithelisation and lesser degree of tissue contracture compared to group II, although these results were not significant statistically (p value = 0.464, 0.705 and 1.000 respectively). Conclusion This study shows that use of collagen graft augmented with rhPDGF-BB could be beneficial in oral cavity reconstruction following resection of small lesions, although further research with larger sample size is proposed to confirm the benefit.

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.

Clinical Evaluation of the Combination of rhPDGF-BB and Xenogeneic Bone Substitutes for Treatment of Severe Periodontal Intrabony Defects: A Case Series.

Growth factors are considered an important component for periodontal wound healing and a key element in the periodontal regeneration triad. Randomized controlled clinical trials have demonstrated that purified recombinant human platelet-derived growth factor-BB (rhPDGF-BB) in combination with bone graft materials is effective in treating intrabony periodontal defects. Many clinicians are currently using rhPDGF-BB in combination with xenogeneic or allogeneic bone. Therefore, the purpose of this case series was to assess the clinical effectiveness of combining rhPDGF-BB with xenogeneic bone substitutes to treat severe intrabony periodontal defects. Three patients with challenging deep and wide intrabony defects were treated using a combination of rhPDGF-BB and xenogeneic graft matrix. Probing depth (PD) reduction, bleeding on probing (BOP), mobility reduction, and radiographic bone fill (RBF) were observed for 12 to 18 months. PD decreased from 9 mm to 4 mm, BOP was eliminated, mobility decreased, and RBF ranged from 85% to 95% over the postsurgical observation period. These results indicate that combination of rhPDGF-BB with xenogeneic bone substitutes is a safe and effective graft that leads to favorable clinical and radiographic outcomes for treating severe intrabony periodontal defects. Larger case series or randomized studies will further elucidate the clinical predictability of this treatment protocol. Int J Periodontics Restorative Dent 2023;43:193-200. doi: 1011607/prd.6313.

PDGF-BB prevents destructive repair and promotes reparative osteogenesis of steroid-associated osteonecrosis of the femoral head in rabbits.

Destructive repair characterized by inadequate angiogenesis and osteogenesis is the main pathological progression in steroid-associated osteonecrosis of the femoral head (SONFH). Platelet-derived growth factor-BB (PDGF-BB) is an "angiogenesis and osteogenesis coupling" factor that has been used for the treatment of bone defects in clinic. This study was designed to analyze the ability of PDGF-BB for preventing destructive repair and promoting reparative osteogenesis in SONFH. Steroid-associated osteonecrosis (SAON) was induced and triggered destructive repair of the femoral head by repeated lipopolysaccharide (LPS) and methylprednisolone (MPS) injections in rabbits. At 2, 4, and 6 weeks after induction, recombinant human PDGF-BB, neutralizing PDGF-BB antibody, or saline was intramedullary injected into the proximal femora. At week 6 after SAON induction, the proximal femora were dissected for bone architecture and histological analysis. C3H10T1/2 cells and HUVECs were used for further mechanistic investigation. After PDGF-BB treatment, type H vessels and leptin receptor-positive (LepR+) mesenchymal stem cells (MSCs) increased in the affected femoral head, and more osteoblastic osteogenesis along the bone surfaces but scattered adipocytes in bone marrow tissue than that in the SAON group. PDGF-BB treatment prevented destructive repair progression and led to 50-70 % of osteonecrotic femoral heads undergoing reparative osteogenesis. In particular, we found that PDGF-BB could mediate MSC self-renewal and maintain their osteogenic potency by activating PDGFR/Akt/GSK3β/CERB signaling in the presence of steroids. Moreover, PDGF-BB also stabled the newly formed vascular tubes by recruiting MSCs for improving intraosseous vascular integration. PDGF-BB may be a candidate for the promotion of reparative osteogenesis in SONFH.

The "Iceberg" Connective Tissue Graft Technique for Peri-implant Papilla Augmentation Following Interproximal Bone Reconstruction.

Implants with deficient papillae and black triangle are common findings. The treatment of these esthetic complications is considered challenging, and with limited predictability. Therefore, the aim of the present report is to describe a novel technique for papilla augmentation (the "Iceberg" connective tissue graft [iCTG]) after extraction and interproximal bone reconstruction in the anterior region. A 35-year-old patient presented with a hopeless tooth with interproximal clinical attachment loss extending up the apical third of the adjacent tooth. Interproximal bone reconstruction was performed through alveolar ridge preservation by directly applying recombinant human platelet-derived growth factor-BB (rhPDGF-BB) to the exposed root surface of the adjacent tooth. A mixture of autogenous bone chips (obtained from the ramus) and bovine bone xenograft particles, previously mixed with the growth factor, was also used. The patient was able to come back for implant therapy only 2 years later. An incomplete regeneration of the interproximal bone was observed. Therefore, to compensate the interproximal deficiency, the iCTG approach, involving a double layer CTG with different origins, was utilized. Two small grafts from the tuberosity were sutured to the mesial and distal ends of a wider CTG harvested from the palate, aiming at gaining additional volume at the interproximal sites. The composite graft was then sutured on top of the implant platform, with the flap that was then released and closed by primary intention. After conditioning of the peri-implant tissues, the case was finalized with a satisfactory outcome. The described iCTG could be an effective approach for reconstructing peri-implant papilla following interproximal bone reconstruction.

Efficacy of biologics for the treatment of periodontal infrabony defects: An American Academy of Periodontology best evidence systematic review and network meta-analysis.

A large variety of biomaterials, biologics and membranes have been utilized in the past 40 years for the regenerative treatment of periodontal infrabony defects. Biologic agents have progressively gained popularity among clinicians and are routinely used for periodontal regeneration. In alignment with the goals of the American Academy of Periodontology (AAP) Best Evidence Consensus (BEC) on the use of biologic mediators in contemporary clinical practice, the aim of this sytematic review was to evaluate the effect of biologic agents, specifically autogenous blood-dervied products (ABPs), enamel matrix derivative (EMD) and recombinant human platelet-derived growth factor-BB (rhPDGF-BB), on the regenerative outcomes of infrabony defects. A detailed systematic search was conducted to identify eligible randomized control trials (RCTs) reporting the outcomes of periodontal regenerative therapy using biologics for the treatment of infrabony defects. A frequentist mixed-modeling approach to network meta-analysis (NMA), characterized by the assessment of three individual components for the treatment of an infrabony defect (the bone graft material [BG], the biologic agent, the application of a barrier membrane) was performed to evaluate and compare the relative efficacy of the different components, on the outcomes of different therapeutic modalities of periodontal regeneration. A total of 153 eligible RCTs were included, with 150 studies contributing to the NMA. The quantitative analysis showed that the addition of biologic agents to bone graft significantly improves the clinical and radiographic outcomes, as compared to BG and flap procedures alone. Barrier membranes enhanced the regenerative outcomes of BG but did not provide further benefits in combination with biologics. The type of BG (autogenous, allogeneic, xenogeneic or alloplastic) and the biologic agent (EMD, platelet-rich fibrin [PRF], platelet-rich plasma [PRP] or rhPDGF-BB) played a significant role on the final outcomes of infrabony defects. Allogeneic and xenogeneic BGs exhibited statistically significantly superior clinical gain than synthetic and autogenous BGs (p<0.05 in all the comparisons), while rhPDGF-BB and PRF demonstrated significantly higher stability of the gingival margin (p<0.01) and radiographic bone fill/gain (p<0.05), together with greater, although not statistically significant, clinical attachment level gain and pocket depth reduction, than EMD and PRP. Overall, rhPDGF-BB exhibited the largest effect size for most parameters, including clinical attachment level gain, pocket depth reduction, less gingival recession and radiographic linear bone gain. Considering the relatively high number of trials presenting an unclear or high risk of bias, the strength of recommendation supporting the use of PRP was judged weak, while the recommendation for EMD, PRF and rhPDGF-BB was deemed in favor. Biologics enhance the outcomes of periodontal regenerative therapy. Combination therapies involving BGs + biologics or BGs + barrier membrane demonstrated to be superior to monotherapies. The choice of the type of BG and biologic agent seems to have significant impact on the clinical and radiographic outcomes of infrabony defects.

Anorganic Bovine Bone Plus Recombinant Human Platelet-Derived Growth Factor-BB in Ridge Preservation: A Pilot Study.

To determine clinical parameters, histologic features, and radiographic linear bone width changes of regenerated bone using different biomaterials for ridge preservation following tooth extraction. For this pilot study, five patients were grafted with anorganic bovine bone and collagen plus recombinant human platelet-derived growth factor-BB (rhPDGF-BB), five patients were grafted with anorganic bovine bone and collagen alone, and five patients did not receive any biomaterial (control) after tooth extraction. Clinical, histologic, and radiographic evaluations were carried out 4 months postextraction. Differences in terms of buccolingual width were found when comparing the control group to the group grafted with anorganic bovine bone and collagen plus rhPDGF-BB (P = .012). No statistical differences were observed between the groups in terms of mineralized or nonmineralized tissue formation or in terms of the number of osteoblasts or osteocytes per mm2 after 4 months of healing. Interestingly, the number of vessels in the grafted area was found to be significantly different among the three groups (P = .005). The number of Musashi-1 positive cells was also different among groups, both in the mineralized and the nonmineralized areas of the grafted bone (P = .024 and .005, respectively). Anorganic bovine bone with bovine collagen is an efficient biomaterial to avoid postextraction resorption of the alveolar ridge. The addition of rhPDGF-BB appears to improve the biologic features of the newly formed bone and decrease bone resorption; further studies are needed for confirmation.

Recombinant human PDGF-BB in combination with mineralized freeze-dried bone allograft in the treatment of Grade II furcation involvement: A case report

Recombinant human platelet-derived growth factor-BB (rhPDGF-BB) is commercially available biomaterial that can be used to regenerate the lost periodontal structure due to progression of periodontitis. The present case describes the surgical treatment of localized periodontitis with furcation Grade II involvement using platelet-derived growth factor BB (growth-factor enhanced matrix 21S) in combination with particulate allograft bone (mineralize freeze-dried bone allograft [FDBA]).This case report showed complete furcation closure after using rhPDGF-BB in combination with FDBA to treat localized periodontitis case with Grade II furcation involvement.

In ovariectomy-induced osteoporotic rat models, BMP-2 substantially reversed an impaired alveolar bone regeneration whereas PDGF-BB failed

We previously suggested an ovariectomy (OVX)-induced osteoporotic rat model showing an impaired alveolar bone defect healing. This study aimed to evaluate and compare the effects of recombinant human bone morphogenetic protein-2 (rhBMP-2) and recombinant human platelet-derived growth factor-BB (rhPDGF-BB) on alveolar bone defect healing in OVX-induced osteoporotic rats. A total of forty-one female rats were divided into four groups: a collagen group (n=10), a PDGF-BB group (n=11), a BMP-2 group (n=10), and a control group (n=10). Four months after OVX, alveolar bone drill-hole defects were created and grafted with collagen gel, rhPDGF-BB/collagen gel, or rhBMP-2/collagen gel. The defects in the control group were not grafted with any material. Defect healing was evaluated by histological, histomorphometric, and microcomputed tomographic (micro-CT) analyses at 2 and 4 weeks. According to the micro-CT analysis, the BMP-2 group exhibited the greatest bone volume fraction among all groups, while the PDGF-BB group did not show significant differences compared with the collagen group. The histomorphometric analysis showed a significantly larger amount of new bone area in the BMP-2 group than in the control and collagen groups at 4 weeks; however, the PDGF-BB group did not reach significant superiority compared with the other groups. Alveolar bone regeneration was significantly enhanced by the local use of rhBMP-2/collagen gel compared with the use of rhPDGF-BB/collagen gel in OVX-induced osteoporotic rats. A treatment modality using rhBMP-2 may be a promising approach to promote alveolar bone regeneration in patients suffering from postmenopausal osteoporosis.

Recombinant Human Platelet-Derived Growth Factor: A Systematic Review of Clinical Findings in Oral Regenerative Procedures.

Aim:The use of recombinant human platelet-derived growth factor–BB (rhPDGF) has received Food and Drug Administration approval for the treatment of periodontal and orthopedic bone defects and dermal wound healing. Many studies have investigated its regenerative potential in a variety of other oral clinical indications. The aim of this systematic review was to assess the efficacy, safety, and clinical benefit of recombinant human platelet-derived growth factor (rhPDGF) use for alveolar bone and/or soft tissue regeneration.Material and Methods:Comprehensive electronic and manual literature searches according to the PRISMA guidelines were performed to identify interventional and observational studies evaluating the regenerative applications of rhPDGF-BB. The primary outcomes were the safety, efficacy, and overall clinical benefit of rhPDGF use in oral regenerative procedures.Results:Sixty-three human clinical studies (mean ± SD follow-up period of 10.7 ± 3.3 mo) were included in the qualitative analysis. No serious adverse effects were reported in any of the 63 studies, aside from the postoperative complications routinely associated with surgical therapy. Use of rhPDGF was shown to be beneficial when combined with allografts, xenografts, and alloplasts (the latter tricalcium phosphate [β-TCP]) for the treatment of periodontal defects and gingival recession. The use of rhPDGF also led to favorable clinical outcomes when combined with allografts or xenografts for guided bone regeneration (GBR) and alveolar ridge preservation. While favorable clinical results support the use of the combination of rhPDGF plus allograft or xenograft for GBR, ARP, and sinus floor augmentation, current data support the use of rhPDGF and alloplasts (e.g., β-TCP) only in periodontal defects and gingival recession.Conclusions:Based on the clinical evidence, rhPDGF is safe and provides clinical benefits when used in combination with bone allografts, xenograft, or β-TCP for the treatment of intrabony and furcation periodontal defects and gingival recession or when used with allografts or xenograft for GBR and ARP (PROSPERO CRD42020142446).Knowledge Transfer Statement:Clinicians should be aware that rhPDGF is a safe and effective approach for the treatment of intrabony and furcation periodontal defects and gingival recession or when used with allografts or xenograft for bone regeneration and alveolar ridge preservation. With consideration of cost and patient preference, this result could lead to more appropriate therapeutic decisions.

Treatment of Multiple Mandibular Gingival Recession Defects Using MCAT Technique and SCTG With and Without rhPDGF-BB: A Randomized Controlled Clinical Trial.

The aim of this randomized controlled trial was to compare the clinical outcomes of modified coronally advanced tunnel technique (MCAT) with subepithelial connective tissue graft (SCTG) with and without recombinant human platelet-derived growth factor-BB (rhPDGF-BB) for mandibular multiple recessions. Twenty-four Miller Class I and III recessions were randomly assigned to a group: test (MCAT+SCTG+rhPDGF-BB) or control (MCAT+SCTG). After 6 months, mean recession-depth reduction was higher in the test group (2.08 ± 0.90 mm) than the control (1.83 ± 0.93 mm). Mean root coverage was achieved, favoring the test group (82.6% ± 23.69%) instead of the control (56.2% ± 28.55%). Complete root coverage for the test group was 58.3%, which was significantly superior to control (16.7%). The use of rhPDGF-BB+SCTG using MCAT offered an advantage of a minimally invasive, predictable method for achieving optimal outcomes.

The Impact of Patient Age on Foot and Ankle Arthrodesis Supplemented with Autograft or an Autograft Alternative (rhPDGF-BB/β-TCP).

Background:A recent survey of orthopaedic surgeons asking about risk factors for nonunion following foot and ankle arthrodesis revealed that patient age is considered to be a relatively low risk factor, despite the potential for autologous graft quality to deteriorate with increasing age. The purpose of the current study was to evaluate the impact of patient age and graft type on fusion rates following hindfoot and ankle arthrodesis.Methods:In this study, we analyzed data from a previously published clinical trial, comparing fusion success in 397 subjects who underwent hindfoot or ankle arthrodesis (597 joints) supplemented with either autograft or an osteoinductive autograft alternative, recombinant human platelet-derived growth factor-BB homodimer carried in beta-tricalcium phosphate (rhPDGF-BB/β-TCP). The odds of fusion success were compared among subjects older or younger than age thresholds of 55, 60, 65, 70, and 75 years. The odds of fusion success were also compared between autograft and rhPDGF-BB/β-TCP among subjects older than each age threshold.Results:In the autograft group, the joints of subjects who were younger than the age thresholds of 60 and 65 years had >2 times the odds of successful fusion compared with those of older subjects. There was no significant difference in the odds of fusion success between the older and younger subjects at the age threshold of 55 years. In the rhPDGF-BB/β-TCP group, there was no significant difference in the odds of successful fusion between older and younger subjects at any age threshold. When the odds of fusion success were compared between the 2 graft materials in subjects who were older than each age threshold, rhPDGF-BB/β-TCP had approximately 2 times the odds of fusion success compared with autograft for all thresholds, except 55 years.Conclusions:The presented evidence suggests that age is an identifiable and concerning risk factor for hindfoot and ankle arthrodesis nonunion, a finding in contrast to the wider perception in the surgeon community. Notably, patients ≥60 years of age had significantly lower odds of fusion success with the use of autograft. The data reveal that use of rhPDGF-BB/β-TCP as an alternative bone-healing adjunct may help mitigate the risk of nonunion when these procedures are performed in the elderly population.Level of Evidence:Prognostic Level II. See Instructions for Authors for a complete description of levels of evidence.

Platelet derived growth factor-BB levels in gingival crevicular fluid of localized intrabony defect sites treated with platelet rich fibrin membrane or collagen membrane containing recombinant human platelet derived growth factor-BB: A randomized clinical and biochemical study.

Development of autologous and recombinant growth factor/matrix combination products represent a new emerging trend in regenerative therapeutics and have gained increasing attention as a strategy to optimize tissue regeneration. The aim of the present study was to evaluate the levels of platelet derived growth factor-BB (PDGF-BB) in gingival crevicular fluid (GCF) during early healing period after the regenerative treatment of intrabony defects using beta tricalcium phosphate (β-TCP) as a bone regeneration material with either platelet rich fibrin (PRF) membrane or collagen membrane (CM) treated with recombinant human PDGF-BB (rhPDGF-BB). Twenty patients (13 males and 7 females) with chronic periodontitis participated in this prospective, randomized clinical and biochemical study. Each patient was randomly assigned to PRF membrane (group A) or CM incorporated with rhPDGF-BB (group B). GCF samples were obtained on days 3, 7, 14, and 30 for evaluation of PDGF-BB levels and alkaline phosphatase (ALP) levels. On days 3 and 7 following surgery, mean levels of PDGF-BB at sites treated with PRF membrane or CM incorporated with rhPDGF-BB as a barrier membrane were not significantly different. PDGF-BB levels decreased significantly in samples collected on days 14 and 30 with significant differences between both the groups. ALP levels significantly increased from day 3 to day 30 but there was no difference between two groups. Within the limitations of the study, both PRF membrane and CM incorporated with rhPDGF-BB showed comparable GCF levels of PDGF-BB initially with PRF showing more sustained levels throughout the study period.

Evaluation of the Efficacy of a 1:1 Mixture of β-TCP and rhPDGF-BB in the Surgical Management of Two- and Three-Wall Intraosseous Defects: A Prospective Clinical Trial.

The aim of this split-mouth clinical and radiographic study was to evaluate and compare the regenerative potential of a combination of recombinant human platelet-derived growth factor-BB (rhPDGF-BB) and beta tricalcium phosphate (β-TCP) to the established technique of bone grafting with β-TCP alone in the surgical management of intraosseous defects. A total of 24 sites in 12 subjects with intraosseous defects were included and randomly divided into test (rhPDGF-BB + β-TCP) and control (β-TCP alone) sites. Clinical parameters were recorded at baseline, 3 months, and 6 months. Radiographic parameters were evaluated at baseline and 6 months. Both groups showed statistically significant reductions of all clinical parameters. Intergroup comparison demonstrated a significantly greater probing pocket depth reduction and clinical attachment level gain in the test group. The mean percentage defect fill was significantly greater in the test group than in the control group at 3 and 6 months, and greater improvement in defect angle was also evident in the test group. Although both groups showed definitive improvements in all parameters, the test group showed significantly better results when used to treat human periodontal intraosseous defects.

Bone Quality and Quantity Alterations After Socket Augmentation with rhPDGF-BB or BMPs: A Systematic Review.

The aim of this study was to systematically analyze the effect of growth factors, particularly recombinant human platelet-derived growth factor-BB (rhPDGF-BB) and bone morphogenetic proteins (BMPs), on volumetric and histomorphometric changes after socket augmentation in comparison with the natural healing sockets. An electronic search of four databases (1965 to February 2017) and a hand search of peer-reviewed journals for relevant articles were performed. Human clinical trials that reported quantitative and qualitative outcomes of soft and hard tissues in socket augmented sites with the use of rhPDGF-BB or BMPs, with a minimum five samples per group, were included. Eight studies, including six randomized controlled trials and two case series, were selected. Five of them used BMPs, and three used rhPDGF-BB. Regarding linear bone width change, the weighted mean difference (WMD) between the sites with and without the use of BMPs was 1.66 mm (95% confidence interval = 0.29 to 3.02 mm, P = .02), favoring the BMP group. In terms of histomorphometric outcome, the WMD of the percentage of vital bone between the sites with the use of rhPDGF-BB and with grafting materials alone was 2.16% (95% confidence interval = -4.61% to 8.93%, P = .53). This systematic review revealed that the use of BMPs in socket augmentation yields better ridge width in comparison with a natural healing socket. However, more studies are needed to warrant the effectiveness when using rhPDGF-BB in socket augmentation procedures.

Recombinant Human Platelet-Derived Growth Factor-BB in Human Alveolar Ridge Augmentation: A Review of the Literature.

The objective of this study was to review the available literature regarding the use of recombinant human platelet-derived growth factor-BB (rhPDGF-BB) in human alveolar ridge augmentation and to assess its effectiveness for this specific use. Three electronic searches of the MEDLINE database were performed. This review noted a wide range of study protocols, carrier systems, study periods, and outcome measures. Within the limits of this literature review, the use of rhPDGF-BB and bone regeneration/ridge augmentation led to greater clinical attachment level gain and bone regeneration prior to implant placement. More controlled clinical studies are needed to establish the effectiveness of rhPDGF-BB in alveolar ridge augmentation.

Fabrication of large-pore mesoporous Ca-Si-based bioceramics for bone regeneration.

Our previous study revealed that mesoporous Ca-Si-based materials exhibited excellent osteoconduction because dissolved ions could form a layer of hydroxycarbonate apatite on the surface of the materials. However, the biological mechanisms underlying bone regeneration were largely unknown. The main aim of this study was to evaluate the osteogenic ability of large-pore mesoporous Ca-Si-based bioceramics (LPMSCs) by alkaline phosphatase assay, real-time PCR analysis, von Kossa, and alizarin red assay. Compared with large-pore mesoporous silica (LPMS), LPMSCs had a better effect on the osteogenic differentiation of dental pulp cells. LPMSC-2 and LPMSC-3 with higher calcium possessed better osteogenic abilities than LPMSC-1, which may be related to the calcium-sensing receptor pathway. Furthermore, the loading capacity for recombinant human platelet-derived growth factor-BB was satisfactory in LPMSCs. In vivo, the areas of new bone formation in the calvarial defect repair were increased in the LPMSC-2 and LPMSC-3 groups compared with the LPMSC-1 and LPMS groups. We concluded that LPMSC-2 and LPMSC-3 possessed both excellent osteogenic abilities and satisfactory loading capacities, which may be attributed to their moderate Ca/Si molar ratio. Therefore, LPMSCs with moderate Ca/Si molar ratio might be potential alterative grafts for craniomaxillofacial bone regeneration.

RhPDGF-BB combined with ADSCs in the treatment of Achilles tendinitis via miR-363/PI3K/Akt pathway.

To investigate the mechanism of recombinant human platelet-derived growth factor-BB (rhPDGF-BB) and human adipose-derived stem cells (hADSCs) in the treatment of Achilles tendinitis. Biomechanical indices of stiffness, stress, and maximum load-to-failure were detected by biomechanical test. mRNA and protein levels of miR-363, p-PI3K/AKT, tendon-related genes Collagen I, Scleraxis (Scx), and Tenascin C (TNC) were measured by qRT-PCR and western blot. The proliferation of hADSCs was accessed by MTT assay. Biomechanical indices of stiffness, stress, and maximum load-to-failure, and mRNA and protein levels of tendon-related genes could be improved by rhPDGF-BB or hADSCs alone, and could be further improved by rhPDGF-BB+hADSCs. rhPDGF-BB and hADSCs downregulated the expression of miR-363 and upregulated the levels of p-PI3K/Akt, and rhPDGF-BB+hADSCs further strengthened these effects. In addition, rhPDGF-BB promoted the proliferation of hADSCs in vitro and upregulated the expression of tendon-related genes. miR-363 mimic downregulated the levels of p-PI3K/Akt, miR-363 inhibitor upregulated the levels of p-PI3K/Akt, and miR-363 mimic and PI3K/Akt pathway inhibitor LY294002 reversed the positive effect of rhPDGF-BB on the proliferation of hADSCs, which suggested that rhPDGF-BB promoted the proliferation of hADSCs via miR-363/PI3K/Akt pathway. Biomechanical indices and tendon-related genes could be improved by rhPDGF-BB and hADSCs. Moreover, rhPDGF-BB promoted the proliferation of hADSCs via miR-363/PI3K/Akt pathway, indicating that rhPDGF-BB combined with ADSCs could treat Achilles tendinitis via miR-363/PI3K/Akt pathway.

Synergistic Effects of Growth Factor, Bone Graft, and Resorbable Barrier Membrane in Management of Dehiscence and Fenestration of Dental Implants

ABSTRACT Aim The present study was primarily designed to evaluate the outcome of guided bone graft regeneration in peri-implant defects by combining recombinant human platelet-derived growth factor-BB (rhPDGF-BB) and granules of beta-tricalcium phosphate (B-TCP) mounted by resorbable biomesh membrane. Secondary objective was to determine the value of resorbable barrier membrane to improve the efficacy of the growth factormediated regeneration. Materials and methods A randomized controlled study comprised 14 participants (8 males and 6 females, mean age 37 years, range 19—55 years), in which a total of 15 implants (10 in maxilla and 5 in the mandible) were placed. Fifteen implant sites were randomly divided by picking a code into three groups: Test group I (n = 5) ß-TCP + rhPDGF (0.3 mg/mL) + biomesh, test group II (n = 5) ß-TCP + rhPDGF, and control (n = 5) ß-TCP + biomesh. The experimental site was examined clinically for the gingival status and radiographically for the bone status. Results Statistically significant difference in preoperative and postoperative measurements was observed for test groups I and II in all the parameters except width; in contrast, there was no significant difference observed for the control group from baseline to 5 months postoperatively. On intergroup comparison, statistically significant difference was observed between test group I vs control group and test group II vs control group, but it was not significant between test groups I and II, which was further confirmed using global performance scale score. Conclusion It concluded that rhPDGF-BB and ß-TCP mounted by resorbable biomesh membrane played a synergistic role in the management of peri-implant defects. Clinical significance Bone regenerated using ß-TCP with rhPDGF-BB in the reversal of peri-implant defects. How to cite this article Arora R, Verma UP, Dixit J, Lal N. Synergistic Effects of Growth Factor, Bone Graft, and Resorbable Barrier Membrane in Management of Dehiscence and Fenestration of Dental Implants. World J Dent 2017;8(3):177-182.

Clinical Outcomes of Nonunions of Hindfoot and Ankle Fusions.

While nonunion after foot and ankle fusion surgery has been associated with poor outcomes, we are not aware of any longitudinal study on this subject. Thus, we prospectively evaluated the impact of nonunion on clinical outcomes of foot and ankle fusions and identified potential risk factors for nonunion after these procedures. Using data from a randomized clinical trial on recombinant human platelet-derived growth factor-BB (rhPDGF-BB; Augment Bone Graft, BioMimetic Therapeutics), union was defined either by assessment of computed tomography (CT) scans at 24 weeks by a reviewer blinded to the type of treatment or by the surgeon's composite assessment of clinical and radiographic findings at 52 weeks and CT findings at 24 or 36 weeks. The nonunion and union groups (defined with each assessment) were then compared in terms of clinical outcome scores on the American Orthopaedic Foot & Ankle Society Ankle-Hindfoot Scale (AOFAS-AHS), Foot Function Index (FFI), and Short Form-12 (SF-12) as well as age, sex, body mass index (BMI), smoking status, diabetes status, work status, and arthrodesis site. Blinded CT assessment identified nonunion in 67 (18%) of 370 patients, and surgeon assessment found nonunion in 21 (5%) of 389 patients. Postoperatively, the nonunion group scored worse than the union group, regardless of the method used to define the nonunion, on the AOFAS-AHS and FFI, with mean differences of 10 and 12 points, respectively, when nonunion was determined by blinded CT assessment and 19 and 20 points when it was assessed by the surgeon. The nonunion group also had worse SF-12 Physical Component Summary scores. Differences between the union and nonunion groups were clinically meaningful for all outcome measures, regardless of the nonunion assessment method. The concept of an asymptomatic nonunion (i.e., imaging indicating nonunion but the patient doing well) was not supported. Patients with nonunion were more likely to be overweight, smokers, and not working. This prospective longitudinal study demonstrated poorer functional outcomes in patients with a nonunion after foot and ankle fusion, regardless of whether the diagnosis of nonunion was based on CT only or on combined clinical, radiographic, and CT assessment. Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.