Recombinant Human Platelet-derived Growth Factor Research Articles

Effect of Recombinant Human Platelet-Derived Growth Factor on Healing of Chronic Periapical Tissue Pathosis Following Apical Surgery in a Canine Model: A Histomorphometric and Microcomputed Tomography Analysis.

This canine in vivo study assessed the effect of recombinant human platelet-derived growth factor (rhPDGF) on the healing of periapical tissues following apical surgery. From a total of 96 premolar teeth, 64 teeth from six beagle dogs (2 years old) were classified as experimental and were randomly assigned to four experimental groups (16 teeth per group). After having the pulp extirpated, leaving teeth open to the oral cavity for 1 week, and sealing with an immediate restorative material for 8 weeks, nonsurgical endodontic treatment was performed. A split-mouth design was used, and intra-animal randomization of treatment sides was applied to the groups as follows: apical curettage + 1.5-mm root-end resection (Group 1); apicoectomy + mineral trioxide aggregate (MTA) root-end filling (Group 2); apicoectomy + MTA root-end filling + rhPDGF (Group 3); and apical curettage + rhPDGF (Group 4). The animals were sacrificed 24 months after apical surgery, and histologic and μCT analyses were performed for bone volume loss (BVL). Group 1 showed partial resolution of the periapical lesions without signs of tissue regeneration (BVL: 49.09 ± 10.97 mm3). Group 2 had minimal bone regeneration and showed cementum reformation in 9 teeth, with no direct attachment to the MTA (BVL: 35.34 ± 10.97 mm3). Group 3 showed regeneration of all damaged apical tissues without direct contact between the cementum and MTA (BLV: 4.51 ± 1.55 mm3). Group 4 showed regeneration of PDL, bone, and cementum and attachment of functional cementum fibers (BVL: 2.82 ± 2.3 mm3). The difference in BVL was statistically significant only for Groups 1 and 2 (P < .05). rhPDGF may help regenerate apical tissue structures following apical surgery.

A Radiohistographic Analysis of Growth Factor-Mediated Sinus Augmentation in Atrophic Maxillae: A 30-Month Follow-up Study.

A total of 20 atrophic maxillary sinuses were augmented with recombinant human platelet-derived growth factor BB (rhPDGF-BB), alloplast, and bovine xenograft using a direct approach. CBCT imaging was performed at baseline, immediately postoperatively, and at 6 and 30 months postoperatively. A histologic evaluation revealed the bone bridging and bone regenerative efficacy of the graft material. Radiographic evaluation determined the ridge height (H) and volume of the graft (V) to be as 3.02 ± 1.35 mm at baseline (H0), 15.18 ± 2.52 mm (H1) and 1,106.10 ± 398.84 mm3 (V1) immediately postoperatively, 14.79 ± 2.30 mm (H2) and 1,086.95 ± 396.86 mm3 (V2) at 6 months, and 1,058 ± 391.83 mm3 (V3) at 30 months, with a significant gain in the residual ridge height at 6 months and no significant loss or gain in sinus volume postoperatively.

A retrospective review of recombinant human platelet-derived growth factor with beta-tricalcium phosphate bone graft substitute use in hindfoot and/or ankle arthrodesis

BackgroundNonunion following foot and ankle arthrodesis can cause chronic pain and disability, poor patient satisfaction, and increased healthcare costs. Nonunion rates are reported in 10%–12% of primary foot and/or ankle arthrodesis procedures, with significantly greater rates among patients with high-risk factors such as smoking, diabetes, obesity, or Charcot neuroarthropathy. Recombinant human platelet-derived growth factor BB-homodimer with beta-tricalcium phosphate (rhPDGF-BB/β-TCP) is a bone graft substitute that has demonstrated efficacy in foot and ankle fusion rates that are comparable to autograft. MethodsCharts and radiographs were retrospectively reviewed on consecutive adult patients undergoing talonavicular, calcaneal-cuboid, subtalar, and/or ankle arthrodesis utilizing rhPDGF-BB/β-TCP bone graft substitute. The primary outcome measures were rate of and mean time to fusion, mean time to return to function, and incidence of adverse events. ResultsThis study reviewed133 patients who underwent 209 hindfoot and/or ankle joint arthrodesis procedures with a mean follow-up 20.34 ± 11.05 months. The overall fusion rate was 92.82% (194/209 joints) with a mean time to fusion of 13.14 ± 2.52 weeks and return to function of 16.56 ± 3.26 weeks. Overall, there were 7 (5.26%) patients who experienced an adverse event (AE) with 15 (7.18%) joints experiencing a nonunion. ConclusionFusion rates with rhPDGF-BB/β-TCP bone grafting material compared favorably to autograft controls when used in hindfoot and/or ankle arthrodesis. No AEwas related to rhPDGF-BB/β-TCP. This study suggests that using rhPDGF-BB/β-TCP is effective in hindfoot and/or ankle arthrodesis, even among patients with comorbidities who are at a higher risk of developing a nonunion. Level of clinical evidence3.

Purification Method Optimization of Recombinant Platelet-Derived Growth Factor rhPDGF-BB Expressed in Methylotrophic Yeast &lt;i&gt;Pichia pastoris&lt;/i&gt;

Recombinant human platelet-derived growth factor rhPDGF-BB is one of the major cytokines, which has been approved for medical use. Medical drug “becaplermin”, containing rhPDGF-BB has been approved for neuropathic ulcer and severe skin burns treatment, as well as in periodontal surgery (in combination with osteoconductive matrices). In this article, we sought to optimize purification process to obtain high purity rhPDGF-BB using methylotrophic yeast Pichia pastoris – a production host for rhPDGF-BB. A faster and simpler chromatography purification method has been suggested which allows to obtain rhPDGF-BB with purity 98% as determined by SDS-PAGE and containing host cell proteins (HCP) 33 ± 4 ng/mg, as measured by ELISA. The effective proliferative dose of rhPDGF-BB measured by WST-1 proliferative assay on 3T3 mouse fibroblast cell culture is 5.02 ± 2.64 ng/mL, which is comparable to commercially available analogues. The optimized method can be attractive for production scale use.

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

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

Efficacy of biologics in root coverage and gingival augmentation therapy: An American Academy of Periodontology best evidence systematic review and network meta-analysis.

The aim of this systematic review was to assess the efficacy of three biologics, namely autologous blood-derived products (ABPs), enamel matrix derivatives (EMD) and recombinant human platelet-derived growth factor BB (rhPDGF-BB), in root coverage and gingival augmentation therapy. The protocol of this PRISMA 2020-compliant systematic review was registered in PROSPERO (CRD42021285917). After study selection, data of interest were extracted. A network meta-analysis (NMA) was conducted to assess the effect of different surgical interventions on the main clinical outcomes of interest (i.e., mean root coverage [MRC%], complete root coverage [CRC%], keratinized tissue width [KTW], gingival thickness [GT] change, and recession depth [RD] reduction). A total of 48 trials reported in 55 articles were selected. All studies reported on the treatment of gingival recession defects for root coverage purposes. Forty-six treatment arms from 24 trials were included in the NMA. These arms consisted of treatment with coronally advanced flap (CAF) alone, EMD+ CAF, platelet-rich fibrin (PRF)+ CAF, and subepithelial connective tissue graft (SCTG)+ CAF. Regarding MRC%, SCTG+CAF was associated with a significant higher estimate (13.41%, 95% CI [8.06-18.75], P< 0.01), while EMD+CAF (6.68%, 95% CI [-0.03 to 13.4], P=0.061) and PRF+CAF (1.03%, 95% CI [-5.65 to 7.72], P=0.71) failed to show statistically significant differences compared with CAF alone (control group) or with each other. Similarly, only SCTG+CAF led to a significantly higher CRC% (14.41%, 95% CI [4.21 to 24.61], P<0.01), while treatment arms EMD+ CAF (13.48%, 95% CI [-3.34 to 30.32], P=0.11) and PRF+CAF (-0.91%, 95% CI [-15.38, 13.57], p=0.81) did not show significant differences compared with CAF alone or with each other. Differences in the CI of PRF+CAF (symmetrical around a zero adjunctive effect) and EMD+CAF (non-symmetrical) suggest that EMD could have some additional value compared with PRF. Treatment with SCTG+CAF led to a statistically significant higher RD reduction (-0.39mm, 95% CI [-0.55 to 0.22], P<0.01), however EMD+CAF (-0.13mm, 95% CI [-0.29 to 0.01], P=0.08) and PRF+CAF (-0.06mm, 95% CI [-0.23 to 0.09], P=0.39) failed to show significant differences compared with CAF or with each other. While SCTG+CAF was associated with a statistically significant higher gain of KTW (0.71mm, 95% CI [0.48 to 0.93], P<0.01), EMD+CAF (0.24mm, 95% CI [-0.02 to 0.51], P=0.08) and PRF+CAF (0.08mm, 95% CI [-0.23 to 0.41], P=0.58) did not result into significant changes compared with CAF alone or with each other. Regarding the use of rhPDGF-BB+CAF, although available studies have reported equivalent results compared with SCTG+CAF, evidence is very limited. The use of ABPs, EMD, or rhPDGF-BB in conjunction with a CAF for root coverage purposes is safe and generally promotes significant improvements respective to baseline clinical parameters. However, the adjunctive use of ABPs and EMD does not provide substantial additional improvements in terms of clinical outcomes and patient-reported outcome measures to those achieved using CAF alone, when baseline KTW is >2mm. Both PRF+CAF and EMD+CAF rendered inferior MRC%, CRC%, RD reduction, and KTW gain compared with SCTG+CAF, which should still be considered the gold-standard in root coverage therapy. Although some studies have reported equivalent results for rhPDGF-BB+CAF compared with the gold-standard intervention, limited evidence precludes formal comparisons with CAF or SCTG+CAF that could be extrapolated to guide clinical practice.

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Journal of Clinical PeriodontologyVolume 49, Issue 11 p. i-i COVER IMAGEFree Access Cover Image First published: 17 October 2022 https://doi.org/10.1111/jcpe.13731AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat Graphical Abstract The cover image is based on the Original Article Recombinant human platelet-derived growth factor improves root coverage of a collagen matrix for multiple adjacent gingival recessions: A triple-blinded, randomized, placebo-controlled trial by Lorenzo Tavelli et al., https://doi.org/10.1111/jcpe.13706. Volume49, Issue11November 2022Pages i-i RelatedInformation

Evidence for Graft Materials Used in Hindfoot and Ankle Arthrodesis: A Systematic Literature Review

Category: Hindfoot; Ankle Introduction/Purpose: There is a wide range of graft materials available to supplement hindfoot and ankle arthrodesis procedures. These include autograft, allografts, and bone graft substitutes. While these various materials are commonly used, the level of evidence to support each has not been widely explored. The purpose of this study was to conduct a systematic literature review to evaluate the level of evidence that exists for each of these materials to inform clinical decision making towards optimal patient outcomes. Methods: A systematic literature review was performed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) statement. The search was conducted using the Embase, MEDLINE, and Cochrane Controlled Register of Trials databases in May 2019 for studies published in English since January 1, 2009. The review included all studies published with patients who were at least 18 years of age needing graft material for hindfoot or ankle arthrodesis. Two independent reviewers reviewed all abstracts for inclusion. Disagreements were resolved by a third reviewer for consensus. Results: The search returned 3,547 records, of which 35 were included. Autograft and allograft had the largest number of studies, most of which were retrospective case series. Recombinant human platelet-derived growth factor BB with beta-tricalcium phosphate (rhPDGF-BB/β-TCP) and autograft were supported by the highest levels of evidence, each having four randomized controlled trials (RCTs). B2A was the only other material in an RCT, but with only24 subjects. Allograft and off-label use of recombinant human bone morphogenetic protein (rhBMP) were supported mainly by retrospective case series. Another assessment of quality was the endpoints. Fusion status was assessed by computed tomography (CT) and/or radiographs, with CT considered superior. Seventeen (17) studies used CT, but the definition of fusion varied from a high barrier of 'at least 50% osseous bridging' in 6 autograft, 5 rhPDGF-BB/β-TCP, 1 rhBMP, 1 demineralized bone matrix, and 1 B2A studies to a lower or undefined criteria in other studies. Conclusion: This literature review reveals the use of grafting materials is supported by a wide range of evidence quality. Most are supported by Level IV evidence, with the exceptions of autograft and rhPDGF-BB/β-TCP. Both are supported by multiple Level I studies. When looking at the methods for assessing fusion status, less than half of studies used CT. Of these, autograft and rhPDGF-BB/β-TCP both had at least 5 studies using CT while other materials had at most 1 study. Surgeons may wish to consider the availability of high-quality evidence, or the lack of, when selecting grafting materials.

Long-Term Follow-Up of Hindfoot and Ankle Arthrodesis Procedures Supplemented with an Autologous Bone Graft Alternative (rhPDGF)

Category: Hindfoot; Ankle Introduction/Purpose: Recombinant human platelet-derived growth factor (rhPDGF) is commonly used in hindfoot and ankle arthrodesis as an alternative to autologous bone graft, the current gold standard grafting material. The largest randomized controlled trial ever conducted in foot and ankle arthrodesis showed that rhPDGF was associated with similar successful radiographic and clinical outcomes to those of autologous bone graft at 24 months. The objective of this study was to determine if outcomes remained similar for these two grafting materials at long-term follow-up. Methods: All 37 sites (414 subjects) from the previously conducted randomized controlled trial examining outcomes for hindfoot and ankle arthrodesis supplemented with either rhPDGF or autologous bone graft (randomized 2:1) were invited to return for a single visit occurring at a minimum follow-up of 60 months. All returning subjects who provided consent were evaluated with computed tomography (CT) scans, American Orthopaedic Foot &amp; Ankle Society (AOFAS) Scores, Foot Pain and Disability (FFI) Scores, and visual analog scores (VAS) assessing fusion site, weight bearing, and graft harvest site pain. Because final fusion status was dependent upon the status exiting the original trial, maintenance or improvement of fusion status was the key focus of the study. The change in baseline from all other outcomes measures were also compared between the two groups. Results: A total of 169 subjects (109 rhPDGF, 60 autologous) from 26 sites completed a follow-up visit at a mean 9.1 years (7.7- 10.9).The rate of maintenance or improvement of CT fusion status was statistically noninferior for subjects in the rhPDGF group compared to the autologous bone graft group (92.7% vs. 95.0%,p=0.021), Total AOFAS Scores (74.9+16.7 vs. 77.2+13.9, p&lt;0.001), FFI Scores (22.7+21.7 vs. 16.5+12.0, p&lt;0.001), weight bearing pain change from baseline (-46.0+33.4 vs. -51.0+33.1, p=0.002), and fusion site pain change from baseline (-34.0+33.6 vs. -34.0+32.4, p&lt;0.001). There were no differences in secondary surgical interventions with the most common reasons being hardware complications (7.3% vs. 8.3%) and non-union (4.6% vs. 1.7%). There were no significant differences in the rates of medically relevant adverse events. In the autologous bone graft group, 3 (5%) subjects continued to experience clinically relevant pain (VAS&gt;20) at their graft harvest site. Conclusion: The outcomes of rhPDGF in hindfoot or ankle arthrodesis were statistically noninferior to those of autologous bone graft at a mean follow-up of 9.1 years. Over 92% of rhPDGF subjects maintained or improved their fusion status. Similarly, the baseline change for all VAS and functional outcomes were non-inferior for the two groups. The exception was clinically significant graft harvest site pain, which only existed in the autologous bone graft group. The results of this study demonstrate that rhPDGF used in hindfoot and ankle arthrodesis is associated with similar long-term radiographic, functional, and clinical outcomes as autologous bone.

Simultaneous Alveolar Ridge Augmentation and Periodontal Regenerative Therapy Leveraging Recombinant Human Platelet-Derived Growth Factor-BB (rhPDGF-BB): A Case Report

Severe alveolar ridge deficiencies in concomitance with periodontal attachment loss can represent a serious clinical challenge in the context of implant therapy. The present case report describes the management of a complex defect in the esthetic zone via ridge augmentation and periodontal regenerative therapy using a biologic material. A systemically healthy 55-year-old man diagnosed with peri-implantitis around an implant in the maxillary left central incisor position and with severe bone loss on the mesial aspect of the maxillary left lateral incisor underwent several surgical interventions to achieve simultaneous vertical ridge augmentation and periodontal regeneration. These interventions included implant removal, bone augmentation using a composite bone graft (autogenous bone + xenograft particles), and a bioactive protein (recombinant human platelet-derived growth factor), soft tissue augmentation using connective tissue grafts, and peri-implant keratinized mucosa width augmentation via a labial gingival graft strip and a xenogeneic collagen matrix. Substantial gains in vertical bone and clinical attachment were achieved, which allowed for delayed implant placement and subsequent completion of tooth replacement therapy with an implant-supported prosthesis. The present case report demonstrates how simultaneous vertical ridge augmentation and periodontal regeneration can be achieved to manage a challenging clinical situation. Key factors to consider in this type of scenario are proximal bone level, tooth mobility, surgical flap design and management, biomaterial selection, and proper treatment sequencing.

Recombinant human platelet-derived growth factor improves root coverage of a collagen matrix for multiple adjacent gingival recessions: A triple-blinded, randomized, placebo-controlled trial.

To evaluate the efficacy of recombinant human platelet-derived growth factor (rhPDGF)-BB combined with a cross-linked collagen matrix (CCM) for the treatment of multiple adjacent gingival recession type 1 defects (MAGRs) in combination with the coronally advanced flap (CAF). Thirty patients were enrolled in this triple-blind, randomized, placebo-controlled trial and treated with either CAF + CCM + rhPDGF, or CAF + CCM + saline. The primary outcome was mean root coverage (mRC) at 6months. Complete root coverage, gain in gingival thickness (GT), keratinized tissue width, volumetric and ultrasonographic changes, and patient-reported outcome measures were also assessed. Mixed-modelling regression analyses were used for statistical comparisons. At 6months, the mRC of the CCM + rhPDGF and CCM alone groups were 88.25% and 77.72%, respectively (p=.02). A significant gain in GT was consistently observed for both treatment arms, and more so for the patients receiving the matrix containing rhPDGF through time (0.51 vs. 0.80 mm, on average, p=.01). The rhPDGF + CCM treated patients presented greater volume gain, higher soft tissue thickness, and a superior aesthetic score. rhPDGF enhances the clinical, volumetric, and aesthetic outcomes of MAGRs above the results achieved with CAF + CCM alone (ClinicalTrials.gov NCT04462237).

Implant Site Development Using Titanium Mesh in the Maxilla: A Retrospective Study of 58 Mesh Procedures in 48 Patients.

This article presents a retrospective case series of implant site development using titanium mesh (Ti-mesh) in the maxilla. A total of 58 mesh procedures in combination with several different bone grafts (allograft, cellular allograft, and bovine xenograft) and biologics (including recombinant human platelet-derived growth factor, autogenous platelet-rich growth factor, and recombinant human bone morphogenetic protein-2) were performed in 48 patients. Ti-mesh guided bone regeneration procedures were performed 2 to 3 months after extraction of nonrestorable/hopeless teeth, and the implants were placed 6 to 8 months postaugmentation. The mean initial ridge width was 2.0 ± 1.0 mm, and the mean horizontal gain after Ti-mesh procedures was 4.7 ± 1.6 mm. The ridge width was first measured on the cross-sectional presurgical CBCT image and then confirmed clinically during surgical procedures. No statistical difference in the horizontal gain was found among different combinations of bone grafts and biomaterials. Ti-mesh exposure occurred 22% of the time. The middle-aged adults (odds ratio [OR] = 8.59; P = .046) and older adults (OR = 16.66; P = .02) had significantly higher chances of mesh exposure compared to young adults. While all implants were successfully placed, about 56% of the implants had < 2 mm of bone to the facial aspect of the osteotomy and received additional contour augmentation when placed in a prosthetically appropriate position for a screw-retained restoration. This study demonstrates that although Ti-mesh procedures result in significant bone regeneration in narrow alveolar ridges to predictably allow implant placement, the age-related mesh exposure rate and frequency of need for additional contour grafting should be discussed with patients.

Biologic Adjuvants for Foot and Ankle Conditions

Orthobiologics are a family of treatments including molecules, cells, or tissues that aid in reparative musculoskeletal processes, employed in the setting of surgical or nonsurgical therapies to supplement bone, cartilage, and tissue regeneration. They are classified as bone grafts, growth factors, stem cell therapy, blood-based preparations, viscosupplementation, and scaffold-based therapy. The most common orthobiologic products used in foot and ankle include platelet-rich plasma (PRP), bone marrow aspirate concentrate (BMAC), bone morphogenic proteins, and platelet derived growth factor (PDGF). While extracorporeal shock wave therapy is not itself a biologic, it does stimulate a biologic response, and is included in this chapter. There is ample level I evidence supporting PRP use for osteochondral lesions of the talus, plantar fasciitis, chronic remitting non-insertional Achilles tendinopathy, and diabetic foot ulcers. PRP may also provide benefit in ankle osteoarthritis and fracture healing. recombinant human PDGF has been consistently proven in level I studies as a safe and effective alternative to autograft to augment ankle and hindfoot fusions, eliminating the morbidity associated with autograft harvesting. Bone marrow aspirate concentrate may be considered as an adjuvant treatment for bone healing, osteochondral lesions of the talus, and Achilles tendon repair. Extracorporeal shock wave therapy is a treatment option for patients with plantar fasciitis and Achilles tendinosis. Cell-based therapies may provide cells capable of osteoblastic differentiation and osteogenic potential, however, further investigation is warranted. In general, orthobiologics have rapidly expanding indications and are becoming increasingly accepted given their clinical benefits of improved pain and function, minimally invasive delivery, and positive safety profiles. To strengthen future evidence-based guidelines for biologic use in foot and ankle, higher evidence studies are required with improved standardization of concentration, treatment protocols, and outcome measures.

Study of glycerol-methanol and sorbitol-methanol mixed feed strategies for recombinant hPDGF-BB production in Pichia pastoris

The recombinant human platelet-derived growth factor type BB (rhPDGF-BB) protein has been approved by FDA for diabetic foot ulcer treatment due to its function of stimulating cell proliferation and wound healing. In this study, the production of rhPDGF-BB from Pichia pastoris is studied in a 7.5 L fermentation using methanol as carbon source and inducer in induction phase. The specific growth rate of the recombinant strain reduced 1.833-fold and rhPDGF-BB productivity reduced 2.13-fold compared to at 0.5 L. To improve growth and protein expression of the strain in induction phase, the mixed feed strategy, in which glycerol or sorbitol was co-fed with methanol at three different molar ratios (1:1, 1:2 and 1:3) was conducted. Using the mixture of glycerol and methanol at the molar ratio 1:2 and the mixture of sorbitol and methanol at the molar ratio 1:3 increased the productivity of rhPDGF-BB protein 1.32-fold (280,48 mg/L) and 1.24-fold (264,15 mg/L), respectively, higher than using only methanol in the induction phase of the fermentation process.

A Multicenter, Retrospective, Case Series of Patients With Charcot Neuroarthropathy Deformities Undergoing Arthrodesis Utilizing Recombinant Human Platelet-derived Growth Factor With Beta-Tricalcium Phosphate

Charcot neuroarthropathy has traditionally been treated using both nonsurgical and surgical strategies. Recently, orthobiologics have been used to promote arthrodesis in Charcot reconstructions, obviating the need for bone graft in some cases. Recombinant human platelet-derived growth factor BB homodimer (rhPDGF-BB) in combination with beta-tricalcium phosphate scaffold (β-TCP) is a bone graft substitute shown to have comparable efficacy to autograft in incidence of foot and ankle fusion. This multicenter, consecutive case series analyzed patients undergoing Charcot reconstructions utilizing rhPDGF-BB/β-TCP for joint fusion. In this cohort, 98 patients (62.24% male) with a mean age of 62.82 ± 10.28 years (range 40-87) had a fusion incidence of 217 of 223 joints (97.31%) with a mean time to fusion of 13.09 ± 4.87 weeks (range 6-30). There were 6 nonunions in the patient population. Fusion was defined as ≥50% osseous bridging based on computed tomography and/or radiographic consolidation, in addition to clinical findings. With an overall complication rate of 26.53% (26/98), adverse events occurring in more than 1 patient limb included hardware failures (n = 7, 7.14%), infection (n = 4, 4.08%), wound dehiscence (n = 4, 4.08%), amputation (n = 3, 3.06%), and death (n = 2, 2.04%). There were no adverse events related to the grafting material. From this review, we found rhPDGF-BB/β-TCP to be a safe and effective graft material that can be considered a viable alternative to autograft, even in high-risk patients such as those with Charcot neuroarthropathy.

Evaluation of Recombinant Human Platelet-Derived Growth Factor or Enamel Matrix Derivative Plus Calcium Hydroxide for Pulp Capping: A Randomized Controlled Human Clinical Trial.

This in vivo study assessed calcium hydroxide's effect as a matrix carrier for recombinant human platelet-derived growth factor (rhPDGF) and enamel matrix protein (EMD) on pulp tissue healing following pulp capping. Intact premolar sites (n = 18) were included. Coronal access and pulpotomy were performed, and each tooth was exposed to the oral cavity for 1 hour before pulp capping was performed. Teeth were randomly assigned to one of the following pulp-capping groups (n = 6 each): Group 1 (CaOH2 only); Group 2 (CaOH2+EMD); and Group 3 (CaOH2+rhPDGF). Coronal access cavities were then sealed. Immediate preoperative, postoperative, and 4-month follow-up radiographs were taken. At 4 months, teeth were extracted atraumatically and histomorphometric and micro-CT analyses were performed. Group 1 showed formation of thin, uneven, highly porous dentin-like structure with tunnel defects (average thickness: 0.18 to 0.19 mm). Lack of continuity of the newly formed tissue and interrupted communication tunnels were seen between the pulpal space and pulp-capping material. Group 2 showed formation of highly dense, nonporous, even-thickness dentin-like structure obliterating multiple areas of the pulp space (average thickness: 0.9 to 0.94 mm). Abundant odontoblast lacunae were present in the pulp and structure. Group 3 showed formation of an inconsistent, uneven dentin-like structure that appeared highly porous (average thickness: 1.04 to 1.05 mm). It was without tunneling, and abundant odontoblastic lacunae were present. No statistically significant differences were found between Groups 2 and 3, but both were richer in newly formed dentin-like structure with more thickness than Group 1 (P < .05). Addition of EMD to CaOH2 can result in multiple root canal calcifications, mostly in the coronal and apical thirds of the canals. The calcified tissue does not appear to resemble secondary dentin in form, shape, amount, or density. Addition of rhPDGF to CaOH2 may not cause root canal calcifications. The newly formed structure differs from secondary dentin in degree of mineralization, porosity, and density.

Regeneration of Secondary Dentin Using Recombinant Human Platelet-Derived Growth Factor and MTA for Pulp Capping: A Randomized Controlled Human Clinical Trial.

This in vivo study assessed the effect of mineral trioxide aggregate (MTA) as a matrix carrier for recombinant human platelet-derived growth factor (rhPDGF) and enamel matrix protein (EMP) on pulp tissue healing following pulp capping. Eighteen intact human premolars scheduled for extraction were included. Coronal access and pulpotomy were performed, and each tooth was left exposed to the oral cavity for 1 hour before pulp capping was performed. Teeth were randomly assigned to one of the following pulp-capping groups (n = 6 each): Group 1 (MTA only); Group 2 (MTA+EMP); or Group 3 (MTA+rhPDGF). Coronal access cavities were then sealed. Immediate preoperative, postoperative, and 4-month follow-up radiographs were taken. At 4 months, the teeth were extracted atraumatically, and histomorphometric and micro-computed tomography (μCT) analyses were performed. Group 1 showed a thin, uneven, irregular dentin-like structure. Its average thickness was 0.3 ± 0.084 mm measured histologically and 0.29 ± 0.091 mm measured by μCT. Group 2 showed of a nonporous, even-thickness dentin-like structure with multiple root-canal obliterations. Highly dense, atubular dentin-like structures associated with presence of odontoblastic lacunae were seen. The structure's average thickness was 0.87 ± 0.09 mm (histologically) and 0.81 ± 0.17 mm (μCT). Group 3 showed a thick and complete 3D continuous seal of newly formed dentin-like structure covering the pulpal space. It resembled secondary dentin in form, porosity, and tubular structural organization, and its average thickness was 0.94 ± 0.02 mm (histologically) and 0.91 ± 0.09 mm (μCT). Groups 2 and 3 showed higher amounts of newly formed dentin-like structure, that was also thicker, than Group 1 (P < .05). No statistically significant differences in structure thickness were found between Groups 2 and 3. The nature of the structure can differ if rhPDGF or EMP is added to MTA for pulp-capping purposes. Combination of rhPDGF and MTA resulted in a newly formed structure resembling secondary dentin, whereas a combination of EMP and MTA produced a nonporous, highly dense dentinal-like structure associated with significant root-canal obliterations.

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.

Recombinant Human Platelet-Derived Growth Factor BB in Combination With a Beta-Tricalcium Phosphate (rhPDGF-BB/β-TCP)-Collagen Matrix as an Alternative to Autograft.

Joint arthrodesis often employs autograft to promote union; graft harvesting can lead to perioperative morbidity. A Canadian randomized controlled trial (RCT) demonstrated that recombinant human platelet-derived growth factor BB homodimer (rhPDGF-BB) combined with beta-tricalcium phosphate (β-TCP)-collagen was a safe, effective alternative to autograft. This multicenter North American RCT compared the safety and efficacy of rhPDGF-BB/β-TCP-collagen with autograft for ankle and hindfoot fusion. Subclassification using propensity scores (PS) incorporated patients from previous trials for enhanced statistical power for noninferiority testing and broader review of treatments. Patients requiring ankle or hindfoot arthrodesis and supplemental bone graft were treated with rhPDGF-BB/β-TCP-collagen (n = 69) or autograft (n = 35). Outcomes included joint fusion on computed tomography (24 weeks), clinical healing status, visual analog scale (VAS) pain, Short-Form 12 (SF-12), American Orthopaedic Foot & Ankle Society (AOFAS) Ankle-Hindfoot Scale, and Foot Function Index (FFI) scores over 52 weeks. PS methodology addressed potential selection bias arising from pooling data among these patients and 2 previous RCTs with similar inclusion criteria, surgical techniques, graft harvest techniques, and outcomes. All 132 rhPDGF-BB/β-TCP-collagen-treated patients and 167 of 189 candidate autograft-treated controls were selected for comparison by an independent statistician blinded to outcomes. In the PS subclassification, 68.1% treatment patients and 68.4% controls achieved >50% osseous bridging at fusion sites. Clinical healing status was achieved in 84.8% of treated patients and 90.7% of controls at 52 weeks. Clinical, functional, and quality of life results demonstrated noninferiority of rhPDGF-BB/β-TCP-collagen to autograft. Safety-related outcomes were equivalent. PS subclassification analysis of 3 RCTs demonstrated that rhPDGF-BB/β-TCP-collagen was as effective as autograft for ankle and hindfoot fusions, with less pain and morbidity than treatment with autograft. Level I, prospective randomized study.

The applications of periodontal gingival surgery. Ⅱ: alternative materials

The main purposes of periodontal graft surgery include achieving root coverage, improving the clinical attachment level and keratinized tissue, and advancing the procedure of periodontal plastic surgery. Autogenous graft, such as subepithelial connective tissue graft-based procedure, provide the best outcomes for mean and complete root coverage, as well as increase in keratinized tissue. However, a disadvantage of the procedure is in the location of the operation itself: the additional surgical site (palate). Therefore, clinicians are always looking for graft substitutes. This article will discuss the evidence supporting the use of 1) acellular dermal matrix (ADM); 2) xenogeneic collagen matrix (XCM); 3) recombinant human platelet-derived growth factor (rhPDGF); 4) enamel matrix derivative (EMD); 5) guided tissue regeneration (GTR); 6) living cellular construct (LCC), all of which are used in conjunction with coronally advanced flaps as alternatives to autogenous donor tissue. The decision tree for treatments of Miller recession-type defects are also discussed.