Recombinant Human Peptide Growth Factors, Bone Morphogenetic Protein-7 (rhBMP7), and Platelet-Derived Growth Factor-BB (rhPDGF-BB) for Osteoporosis Treatment in an Oophorectomized Rat Model.

Bone morphogenetic protein (BMP) and platelet-derived growth factor (PDGF) are known to regulate/stimulate osteogenesis, playing vital roles in bone homeostasis, rendering them strong candidates for osteoporosis treatment. We evaluated the effects of recombinant human BMP-7 (rhBMP7) and PDGF-BB (rhPDGF-BB) in an oophorectomy-induced osteoporosis rat model. Forty Sprague Dawley rats underwent oophorectomy surgery; treatments commenced on the 100th day post-surgery when all animals exhibited signs of osteoporosis. These peptide growth factors were administered intraocularly (iv) once or twice a week and the animals were monitored for a total of five weeks. Two weeks after the conclusion of the treatments, the animals were euthanized and tissues were collected for assessment of alkaline phosphatase, X-ray, micro-CT, and histology. The results indicate that the most promising treatments were 20 µg/kg rhPDGF-BB + 30 µg/kg rhBMP-7 twice a week and 30 µg/kg BMP-7 twice a week, showing significant increases of 15% (p < 0.05) and 13% (p < 0.05) in bone volume fraction and 21% (p < 0.05) and 23% (p < 0.05) in trabecular number, respectively. In conclusion, rhPDGF-BB and rhBMP-7 have demonstrated the ability to increase bone volume and density in this osteoporotic animal model, establishing them as potential candidates for osteoporosis treatment.

COL1A1::PDGFB fusion-associated uterine fibrosarcoma: A case report and review of the literature.

BACKGROUND: Mesenchymal neoplasms of the uterus encompass a diverse group of tumors, with varying characteristics and origins, collectively accounting for 8% of uterine malignancies. The most common variants include uterine leiomyosarcoma, low-grade and high-grade endometrial stromal sarcoma, adenosarcoma, and undifferentiated sarcoma. Clinical presentation is often nonspecific and can lead to delayed diagnosis. Uterine sarcomas are generally aggressive, resulting in poorer prognosis compared to carcinomas. Recent advances in molecular techniques, such as next-generation sequencing (NGS), have led to the identification of new subtypes of uterine sarcomas, including COL1A1::PDGFB fusion-associated fibrosarcoma, which has a specific chromosomal translocation t(17;22)(q22;q13). Imatinib, a tyrosine kinase inhibitor (TKI), is an effective treatment for dermatofibrosarcoma protuberans (DFSP), marked by this translocation. CASE: We present the case of a 42-year-old woman diagnosed with COL1A1::PDGFB fusion-associated uterine fibrosarcoma. The patient underwent total hysterectomy and excision of the tumor, initially misdiagnosed as a low-grade leiomyosarcoma. Subsequent histological examination, immunohistochemistry, and fluorescence in situ hybridization (FISH) confirmed the diagnosis. After 10 months, disease recurrence was detected, and Imatinib therapy was initiated at a dose of 400 mg daily. An allergic reaction led to a temporary discontinuation, but upon resumption with appropriate medication, a positive radiological response was observed. The patient achieved a complete remission after 2 years and is still on Imatinib treatment. CONCLUSIONS: COL1A1::PDGFB fusion-associated uterine fibrosarcoma is an extremely rare mesenchymal neoplasm. In a case we present herein, we treated a patient with imatinib as first-line medical therapy. The patient is currently in complete remission after 37 months from treatment start. To the best of our knowledge, this represents a unique observation. We also provide a detailed literature review of the published cases so far. Prospective case series are needed to further understand the natural history of these tumors and optimize treatment strategies.

Cold to Hot: Tumor Immunotherapy by Promoting Vascular Normalization Based on PDGFB Nanocomposites.

Immunotherapy is a promising cancer therapeutic strategy. However, the "cold" tumor immune microenvironment (TIME), characterized by insufficient immune cell infiltration and immunosuppressive status, limits the efficacy of immunotherapy. Tumor vascular abnormalities due to defective pericyte coverage are gradually recognized as a profound determinant in "cold" TIME establishment by hindering immune cell trafficking. Recently, several vascular normalization strategies by improving pericyte coverage have been reported, whereas have unsatisfactory efficacy and high rates of resistance. Herein, a combinatorial strategy to induce tumor vasculature-targeted pericyte recruitment and zinc ion-mediated immune activation with a platelet-derived growth factor B (PDGFB)-loaded, cyclo (Arg-Gly-Asp-D-Phe-Lys)-modified zeolitic imidazolate framework 8 (PDGFB@ZIF8-RGD) nanoplatform is proposed. PDGFB@ZIF8-RGD effectively induced tumor vascular normalization, which facilitated trafficking and infiltration of immune effector cells, including natural killer (NK) cells, M1-like macrophages and CD8+ T cells, into tumor microenvironment. Simultaneously, vascular normalization promoted the accumulation of zinc ions inside tumors to trigger effector cell immune activation and effector molecule production. The synergy between these two effects endowed PDGFB@ZIF8-RGD with superior capabilities in reprogramming the "cold" TIME to a "hot" TIME, thereby initiating robust antitumor immunity and suppressing tumor growth. This combinatorial strategy for improving immune effector cell infiltration and activation is a promising paradigm for solid tumor immunotherapy.

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.

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

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

Penehyclidine Hydrochloride Protects Rat Cardiomyocytes from Ischemia- Reperfusion Injury by Platelet-derived Growth Factor-B.

AIMS AND OBJECTIVE: The lack of effective treatments for myocardial ischemiareperfusion (MI-R) injury severely restricts the effectiveness of the treatment of ischemic heart disease. In the present research, we aimed to investigate the protective effect and molecular mechanism of penehyclidine hydrochloride (PHC) on MI-R cells. METHODS: Cell viability was quantified using CCK8. Cell apoptosis was analyzed using flow cytometry. Western blot and Elisa assays were used for the detection of target proteins. RESULTS: PHC pretreatment attenuated the inhibition of cell viability and decreased the percentage of apoptosis induced by simulated ischemia reperfusion (SIR). Platelet-derived growth factor B (PDGF-B) and its downstream AKT pathway were activated in PHC pretreated cells. After siRNAPDGF- B transfection, cell viability was inhibited and apoptosis was activated in PHC pretreated SIR cells, suggesting that PHC protected cells from SIR. PDGF-B knockdown also increased the levels of CK, LDH, IL-6 and TNF-α in PHC pretreated SIR cells. The effect of AKT inhibitor on H9C2 cells was consistent with that of PDGF-B knockdown. CONCLUSION: PHC pretreatment can protect cardiomyocytes from the decrease of cell activity and the increase of apoptosis caused by reperfusion through up-regulating PDGF-B to activate PI3K pathway. Our study indicates that PHC is a potential drug to protect cells from reperfusion injury and PDGF-B is a potential target for preventing MI-R injury.

Effect of Aerosol Inhalation Combined With a Vibration Expectoration Machine on Sputum Volume, IGF-1, α1-AT and PDGF-B in Patients With Chronic Obstructive Pulmonary Emphysema.

Objective: Aerosol inhalation is commonly used in the treatment of chronic obstructive pulmonary emphysema (COPE). This study aimed to evaluate the effectiveness of aerosol inhalation combined with a vibration expectoration machine on COPE. Methods: From June 2019 to June 2020, 110 patients receiving COPE treatment in Linyi Central Hospital in China were included in this randomized controlled trial. All patients were randomly assigned into one of two groups using the random number table. A total of 55 patients were given aerosol inhalation combined with the use of a vibration expectoration machine in the study group, and 55 patients were given aerosol inhalation alone in the control group. The general data, clinical efficacy arterial blood gas index, pulmonary function index and serum levels of insulin-like growth factor 1 (IGF-1), alpha 1 antitrypsin (α1-AT) and platelet-derived growth factor-B (PDGF-B) were compared. Results: There was no difference in baseline characteristics between the 2 groups (P > .05). After treatment, the clinical efficacy in the study group was significantly higher than in the control group (96.36% vs 81.82%, respectively; P = .023), daily sputum production in the study group was significantly higher compared with the control group (80.92 ± 10.29 vs 58.63 ± 9.02 ml, respectively; P < .001) and hospitalization time was significantly reduced in the study group (11.87 ± 1.76 vs 17.62 ± 1.92 days, respectively; P < .001). In addition, the respiratory rate was significantly lower in the study group (17.43 ± 1.61 vs 22.08 ± 3.25, respectively; P < .001). Partial pressure of oxygen (P[O2]) was significantly higher (76.29 ± 7.34 vs 66.81 ± 7.93 mmHg, respectively; P < .001) and partial pressure of carbon dioxide (P[CO2]) was significantly lower (34.82 ± 6.02 vs 39.83 ± 6.01 mmHg respectively; P < .001) in the study group compared with the control group. In addition, forced expiratory volume in the first second (FEV1) (1.79 ± 0.36 vs 1.66 ± 0.28 L, respectively), forced vital capacity (FVC) (2.58 ± 0.28 vs 2.42 ± 0.11 L, respectively), forced expiratory volume in the first second as a percentage of the predicted value (FEV1%pred) (65.32 ± 4.03 vs 59.83 ± 4.76 L, respectively) and maximal mid-expiratory flow (MMEF) (1.51 ± 0.27% vs 1.36 ± 0.12%, respectively) were all significantly increased after treatment in the study group compared with the control group (all P < .001). The IGF-1 (104.92 ± 11.27 vs 137.83 ± 11.02 ng/mL, respectively) and PDGF-B (124.39 ± 14.29 vs 249.93 ± 33.49 ng/L, respectively) were significantly reduced in the study group after treatment (all P < .001). The α1-AT (2.82 ± 0.38 vs 2.17 ± 0.22 g/L, respectively) were significantly increased after treatment in the study group compared with the control group. Conclusion: Aerosol inhalation combined with the use of a vibration expectoration machine is worthy of clinical application, and can effectively improve outcomes in patients with COPE.

Combined MEK/PD-L1 Inhibition Alters Peripheral Cytokines and Lymphocyte Populations Correlating with Improved Clinical Outcomes in Advanced Biliary Tract Cancer.

PURPOSE: Biliary tract cancers (BTC) are aggressive malignancies refractory to chemotherapy and immunotherapy. MEK inhibition (MEKi)-based regimens may have utility in this disease when combined with PD-L1 blockade. We hypothesize that dual MEK/PD-L1 inhibition alters circulating soluble and cellular immune mediators to improve clinical outcomes in patients with advanced BTC. EXPERIMENTAL DESIGN: We examined immune features in peripheral blood from 77 patients with advanced BTC enrolled in a phase II clinical trial investigating atezolizumab with or without cobimetinib. Plasma and peripheral blood mononuclear cells (PBMC) were isolated from whole blood to evaluate soluble factors and immune cell populations. Baseline blood samples were additionally compared with healthy donors to identify immune signatures unique to BTC. RESULTS: At baseline, the soluble factors platelet-derived growth factor B (PDGF)-BB, placental growth factor (PlGF)-1, IL5, and IL17A were elevated in patients with BTC compared with healthy adult donors, and higher baseline frequencies of CD8+BTLA+ T cells correlated with better overall survival (OS) in this trial. There were also significant treatment-related alterations in several factors, including decreased PDGF-BB following combination treatment, that correlated with improved OS and progression-free survival (PFS). Higher baseline levels of IL23 and RANTES corresponded to improved clinical outcomes following combination treatment. Dual MEK/PD-L1 inhibition increased populations of CD4+TIM3+ and decreased CD8+VISTA+ T cells, correlating with worse OS and better PFS, respectively. CONCLUSIONS: This work represents a comprehensive analysis of peripheral immune features in patients with BTC and systemic responses to dual MEK/PD-L1 inhibition. These data support further investigation to understand how MEKi combines with immunotherapeutic approaches to improve clinical outcomes for patients with advanced BTC.

PDGFB targeting biodegradable FePt alloy assembly for MRI guided starvation-enhancing chemodynamic therapy of cancer.

The application of chemodynamic therapy (CDT) for cancer is a serious challenge owing to the low efficiency of the Fenton catalyst and insufficient H2O2 expression in cells. Herein, we fabricated a PDGFB targeting, biodegradable FePt alloy assembly for magnetic resonance imaging (MRI)-guided chemotherapy and starving-enhanced chemodynamic therapy for cancer using PDGFB targeting, pH-sensitive liposome-coated FePt alloys, and GOx (pLFePt-GOx). We found that the Fenton-catalytic activity of FePt alloys was far stronger than that of traditional ultrasmall iron oxide nanoparticle (UION). Upon entry into cancer cells, pLFePt-GOx nanoliposomes degraded into many tiny FePt alloys and released GOx owing to the weakly acidic nature of the tumor microenvironment (TME). The released GOx-mediated glucose consumption not only caused a starvation status but also increased the level of cellular H2O2 and acidity, promoting Fenton reaction by FePt alloys and resulting in an increase in reactive oxygen species (ROS) accumulation in cells, which ultimately realized starving-enhanced chemodynamic process for killing tumor cells. The anticancer mechanism of pLFePt-GOx involved ROS-mediated apoptosis and ferroptosis, and glucose depletion-mediated starvation death. In the in vivo assay, the systemic delivery of pLFePt-GOx showed excellent antitumor activity with low biological toxicity and significantly enhanced T2-weighted magnetic resonance imaging (MRI) signal of the tumor, indicating that pLFePt-GOx can serve as a highly efficient theranostic tool for cancer. This work thus describes an effective, novel multi-modal cancer theranostic system.

Diverse roles of tumor-stromal PDGFB-to-PDGFRß signaling in breast cancer growth and metastasis.

Over the last couple of decades, it has become increasingly apparent that the tumor microenvironment (TME) mediates every step of cancer progression and solid tumors are only able to metastasize with a permissive TME. This intricate interaction of cancer cells with their surrounding TME, or stroma, is becoming more understood with an ever greater knowledge of tumor-stromal signaling pairs such as platelet-derived growth factors (PDGF) and their cognate receptors. We and others have focused our research efforts on understanding how tumor-derived PDGFB activates platelet-derived growth factor receptor beta (PDGFRß) signaling specifically in the breast cancer TME. In this chapter, we broadly discuss PDGF and PDGFR expression patterns and signaling in normal physiology and breast cancer. We then detail the expansive roles played by the PDGFB-to-PDGFRß signaling pathway in modulating breast tumor growth and metastasis with a focus on specific cellular populations within the TME, which are responsive to tumor-derived PDGFB. Given the increasingly appreciated importance of PDGFB-to-PDGFRß signaling in breast cancer progression, specifically in promoting metastasis, we end by discussing how therapeutic targeting of PDGFB-to-PDGFRß signaling holds great promise for improving current breast cancer treatment strategies.

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

PURPOSE: To determine clinical parameters, histologic features, and radiographic linear bone width changes of regenerated bone using different biomaterials for ridge preservation following tooth extraction. MATERIALS AND METHODS: 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. RESULTS: 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). CONCLUSION: 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.

Platelet-derived growth factor B restores vascular barrier integrity and diminishes permeability in ovarian hyperstimulation syndrome.

Although advances in the prediction and management of ovarian hyperstimulation syndrome (OHSS) have been introduced, complete prevention is not yet possible. Previously, we and other authors have shown that vascular endothelial growth factor, angiopoietins (ANGPTs) and sphingosine-1-phosphate are involved in OHSS etiology. In addition, we have demonstrated that ovarian protein levels of platelet-derived growth factor (PDGF) ligands -B and -D decrease in an OHSS rat model, whilst PDGFR-ß and ANGPT2 remain unchanged. In the present work, we investigated the role of PDGF-B in OHSS by evaluating ligand protein levels in follicular fluid (FF) from women at risk of developing OHSS and by using an immature rat model of OHSS. We demonstrated that PDGF-B and PDGF-D are lower in FF from women at risk of developing OHSS compared to control patients (P < 0.05). In the OHSS rat model, PDGF-B (0.5 µg/ovary) administration decreased ovarian weight (P < 0.05), reduced serum progesterone (P < 0.05) and lowered the percentage of cysts (P < 0.05), compared to untreated OHSS rats, but had no effect on the proportion of follicles or corpora lutea (CL). PDGF-B treatment also restored the expression of steroidogenic acute regulatory protein (P < 0.05) and P450 cholesterol side-chain cleavage enzyme (P < 0.01) to control levels. In addition, PDGF-B increased the peri-endothelial cell area in CL and cystic structures, and reduced vascular permeability compared to untreated OHSS ovaries. Lastly, PDGF-B increased the levels of junction proteins claudin-5 (P < 0.05), occludin (P < 0.05) and ß-catenin (P < 0.05), while boosting the extracellular deposition of collagen IV surrounding the ovarian vasculature (PP < 0.01), compared to OHSS alone. In conclusion, our findings indicate that PDGF-B could be another crucial mediator in the onset and development of OHSS, which may lead to the development of novel prediction markers and therapeutic strategies.

Platelet-derived growth factor B attenuates lethal sepsis through inhibition of inflammatory responses.

Sepsis is a systemic inflammatory response during infection and remains a major clinical problem with high morbidity and mortality. Platelet-derived growth factor B (PDGF-B) is a member belongs to PDGF family and has been recently reported higher expressed in survivors of severe sepsis patients. However, the exact role and underlying mechanisms of PDGF-BB in sepsis remains unclear. In this study, we found that PDGF-BB levels were significantly elevated in patients with sepsis, and higher PDGF-BB levels were negatively correlated with the levels of proinflammatory cytokines (TNF-α, IL-6, IL-1ß, IL-8), and chemokines (CXCL-1 and CCL2). PDGF-BB was also found increased in experimental sepsis in mice. Blockade of PDGF-BB using Tyrphostin AG 1296 aggravated, whereas recombinant PDGF-BB treatment improved survival and tissues injury in both two murine models of CLP-induced sepsis and LPS- induced endotoxemia. PDGF-BB blockade increased, whereas PDGF-BB administration decreased the inflammatory responses, as reflected by proinflammatory cytokines (TNF-α, IL-6, IL-1ß, IL-8), and chemokines (CXCL-1 and CCL2). PDGF-BB also showed inhibitory effect on immune cell activation and cytokines production in vivo and in vitro. Therefore, our findings suggest that PDGF-BB plays a protective role in sepsis by decreasing the production of pro-inflammatory cytokines and chemokines. PDGF-BB thus may be a potential therapeutic strategy for treating sepsis.

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

PURPOSE: 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. MATERIALS AND METHODS: Three electronic searches of the MEDLINE database were performed. RESULTS: This review noted a wide range of study protocols, carrier systems, study periods, and outcome measures. CONCLUSION: 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.

PDGF Restores the Defective Phenotype of Adipose-Derived Mesenchymal Stromal Cells from Diabetic Patients.

Diabetes is a chronic metabolic disorder that affects 415 million people worldwide. This pathology is often associated with long-term complications, such as critical limb ischemia (CLI), which increases the risk of limb loss and mortality. Mesenchymal stromal cells (MSCs) represent a promising option for the treatment of diabetes complications. Although MSCs are widely used in autologous cell-based therapy, their effects may be influenced by the constant crosstalk between the graft and the host, which could affect the MSC fate potential. In this context, we previously reported that MSCs derived from diabetic patients with CLI have a defective phenotype that manifests as reduced fibrinolytic activity, thereby enhancing the thrombotic risk and compromising patient safety. Here, we found that MSCs derived from diabetic patients with CLI not only exhibit a prothrombotic profile but also have altered multi-differentiation potential, reduced proliferation, and inhibited migration and homing to sites of inflammation. We further demonstrated that this aberrant cell phenotype is reversed by the platelet-derived growth factor (PDGF) BB, indicating that PDGF signaling is a key regulator of MSC functionality. These findings provide an attractive approach to improve the therapeutic efficacy of MSCs in autologous therapy for diabetic patients.

Effects of PDGF-BB delivery from heparinized collagen sutures on the healing of lacerated chicken flexor tendon in vivo.

Flexor tendon lacerations are traditionally repaired by using non-absorbable monofilament sutures. Recent investigations have explored to improve the healing process by growth factor delivery from the sutures. However, it is difficult to conjugate growth factors to nylon or other synthetic sutures. This study explores the performance of a novel electrochemically aligned collagen suture in a flexor tendon repair model with and without platelet derived growth factor following complete tendon laceration in vivo. Collagen suture was fabricated via electrochemical alignment process. Heparin was covalently bound to electrochemically aligned collagen sutures (ELAS) to facilitate affinity bound delivery of platelet-derived growth factor-BB (PDGF-BB). Complete laceration of the flexor digitorum profundus in the third digit of the foot was performed in 36 skeletally mature White Leghorn chickens. The left foot was used as the positive control. Animals were randomly divided into three groups: control specimens treated with standard nylon suture (n=12), specimens repaired with heparinated ELAS suture without PDGF-BB (n=12) and specimens repaired with heparinated ELAS suture with affinity bound PDGF-BB (n=12). Specimens were harvested at either 4weeks or 12weeks following tendon repair. Differences between groups were evaluated by the degree of gross tendon excursion, failure load/stress, stiffness/modulus, absorbed energy at failure, elongation/strain at failure. Quantitative histological scoring was performed to assess cellularity and vascularity. Closed flexion angle measurements demonstrated no significant differences in tendon excursion between the study groups at 4 or 12weeks. Biomechanical testing showed that the group treated with PDGF-BB bound heparinated ELAS suture had significantly higher stiffness and failure load (p<0.05) at 12-weeks relative to both heparinated ELAS suture and nylon suture. Similarly, the group treated with PDGF-BB bound suture had significantly higher ultimate tensile strength and Young's modulus (p<0.05) at 12-weeks relative to both ELAS suture and nylon suture. Compared to nylon controls, heparinized ELAS with PDGF-BB improved biomechanics and vascularity during tendon healing by 12-weeks following primary repair. The ability of ELAS to deliver PDGF-BB to the lacerated area of tendon presents investigators with a functional bioinductive platform to improve repair outcomes following flexor tendon repair. STATEMENT OF SIGNIFICANCE: A high strength aligned collagen suture was fabricated via linear electrocompaction and heparinized for prolonged delivery of PDFG-BB. When it was used to suture a complete lacerated flexor tendon in a chicken model controlled release of the PDGF-BB improved the strength of treated tendon after 12 weeks compared to tendon sutured with commercial nylon suture. Furthermore, Collagen suture with affinity bound PDGF-BB enhanced the vascularization and remodeling of lacerated tendon when it compare to synthetic nylon suture. Overall, electrocompacted collagen sutures holds potential to improve repair outcome in flexor tendon surgeries by improving repair strength and stiffness, vascularity, and remodeling via sustained delivery of the PDGF-BB. The bioinductive collagen suture introduces a platform for sustained delivery of other growth factors for a wide-array of applications.

Subperiosteal Minimally Invasive Aesthetic Ridge Augmentation Technique (SMART): A New Standard for Bone Reconstruction of the Jaws.

Traditional guided bone regeneration techniques include flap mobilization and placement of a bone graft, often with the use of space-maintaining devices and cell-occlusive membranes. This approach is associated with frequent complications that negatively affect the outcome of the augmentation and the peri-implant soft tissue esthetics. Although current tunneling techniques have focused on periodontal soft tissue applications, earlier publications described their use for horizontal augmentation of mandibular posterior edentulous ridges in full-denture patients. More recently, the use of recombinant human platelet-derived growth factor (rhPDGF-BB) was tested with different bone matrices to treat maxillary anterior edentulous spans. The present case series reports the use of a subperiosteal minimally invasive aesthetic ridge augmentation technique (SMART) to treat 60 single and multiple edentulous, dentate, and implant sites on 21 patients and five treatment categories with a follow-up period ranging from 4 to 30 months. The technique includes the use of a laparoscopic approach to deliver a growth factor/xenograft combination into a subperiosteal pouch. No flap elevation, cell-occlusive membranes, space-maintaining devices, or decortication procedures were used. The results from this case series demonstrated predictable and consistent bone regeneration. The average gain in ridge width for all treatment categories was 5.11 mm (SD 0.76 mm), which compares favorably with previously published reports. Morbidity and complication rates were consistently reduced as well. Human histology results show xenograft particles surrounded by newly formed bone. The role of the periosteum as a source of pluripotent cells in growth factor­mediated bone regeneration is discussed.

The Use of Recombinant Human Platelet-Derived Growth Factor for Maxillary Sinus Augmentation.

The maxillary sinus augmentation procedure has become a predictable treatment to regenerate bone for implant placement. The purpose of this study was to evaluate the effect of recombinant human platelet-derived growth factor BB (rhPDGF-BB) combined with a deproteinized cancellous bovine bone graft for sinus augmentation. The lateral window approach was used for maxillary sinuses with minimal residual bone. After a healing period of 4 months, dental implants were placed and then restored following a 2-month osseointegration period. The result demonstrated increased bone height and ISQ values and a 100% survival rate. This study indicates that the addition of rhPDGF-BB to deproteinized cancellous bovine bone accelerated the healing period in maxillary sinuses with minimal native bone.

Recombinant human platelet-derived growth factor-BB versus autologous bone graft in foot and ankle fusion: A systematic review and meta-analysis.

Today, autogenous bone graft (ABG) is still considered as the gold standard for joint fusion. Recombinant human platelet-derived growth factor-BB (rhPDGF-BB) which is of chemotactic and mitogenic to mesenchymal stem cells and possesses outstanding osteogenetic potentials has been used for ankle and foot fusion in recent years. The goal of this article is to evaluate the safety and efficacy of rhPDGF-BB versus ABG in foot and ankle fusion. The PubMed MEDLINE, EMBASE, Web of Science, and Cochrane Library were systematic searched. Finally, three randomized controlled trials (RCTs) with 634 patients were enrolled in this study. Results of radiologic effectiveness which included CT and radiographic union rates revealed that there was no significant difference between rhPDGF-BB approach and ABG approach. Analysis of clinical results held the same outcomes expect that ABG group was superior in long-term Short Form-12 physical component scores. The pooled results also demonstrated that rhPDGF-BB was as safe as ABG in foot and ankle surgery. However, autograft harvesting procedure has some drawbacks such as donor-site pain and morbidity, additional operation time, blood loss, and scarring, which can be overcome by rhPDGF-BB. Thus, rhPDGF-BB is a viable alternative to autograft in foot and ankle fusion surgery. Yet, more high-quality RCTs with long-term follow-up are still required to make the final conclusion.

Localized bone regeneration around dental implants using recombinant bone morphogenetic protein-2 and platelet-derived growth factor-BB in the canine.

OBJECTIVES: To test whether or not one of two biological mediators (recombinant human bone morphogenetic protein-2 (rhBMP-2) and recombinant human platelet-derived growth factor (rhPDGF-BB)) is superior to the other and compared with control groups for bone regeneration around implants based on histomorphometrical outcome measures. MATERIALS AND METHODS: Box-type defects (10 × 5 × 5 mm) were prepared on the buccal sides of the left and right edentulous ridge in ten mongrel dogs. Implants were placed at each site, the defects either received (i) bovine-derived particulated bone mineral (DBBM) mixed with rhBMP-2 and a collagen membrane (CM) (DBBM/BMP-2), (ii) DBBM mixed with rhPDGF-BB and CM (DBBM/PDGF), (iii) DBBM and CM (DBBM) and (iv) empty control (control). Animals were euthanized post-surgery at 8 weeks and 16 weeks. Histomorphometrical analyses were performed. RESULTS: The mean percentages of regenerated area within total defect area amounted to 56.95% for DBBM/BMP-2, 48.86% for DBBM/PDFG, 33.44% for DBBM and 1.59% for control at 8 weeks, and 26.79% for DBBM/BMP-2, 23.78% for DBBM/PDFG, 30.21% for DBBM and 5.07% for control at 16 weeks with no statistically significant differences between the groups (P > 0.05). The mean amount of regenerated bone was 26.97% for DBBM/BMP-2, 22.02% for DBBM/PDFG, 5.03% for DBBM and 1.25% for control at 8 weeks, and at 16 weeks, these values were lower in the two groups with biological mediators (DBBM/BMP-2 = 13.35%; DBBM/PDGF = 6.96%) and only slightly increased in group DBBM (10.68%) and the control group (4.95%) compared with 8 weeks. The first bone-to-implant contact values on the buccal side were minimal for DBBM/BMP-2 (0.57 mm) and maximal for control (3.72 mm) at 8 weeks. CONCLUSIONS: The use of biological mediators (rhBMP-2 and rhPDGF-BB) can increase the amount of bone regeneration at dehiscence-type defects compared with controls at 8 weeks, but not at 16 weeks due to enhanced hard tissue remodeling processes.