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Non-union during healing of bone fractures affects up to ~5% of patients worldwide. Given the success of recombinant human platelet-derived growth factor-B chain homodimer (rhPDGF-BB) in promoting angiogenesis and bone fusion in the hindfoot and ankle, rhPDGF-BB combined with bovine type I collagen/β-TCP matrix (AIBG) could serve as a viable alternative to autografts in the treatment of non-unions. Defects (~2 mm gaps) were surgically induced in tibiae of skeletally mature New Zealand white rabbits. Animals were allocated to one of four groups-(1) negative control (empty defect, healing for 8 weeks), (2 and 3) acute treatment with AIBG (healing for 4 or 8 weeks), and (4) chronic treatment with AIBG (injection 4 weeks post defect creation and then healing for 8 weeks). Bone formation was analyzed qualitatively and semi-quantitatively through histology. Samples were imaged using dual-energy X-ray absorptiometry and computed tomography for defect visualization and volumetric reconstruction, respectively. Delayed healing or non-healing was observed in the negative control group, whereas defects treated with AIBG in an acute setting yielded bone formation as early as 4 weeks with bone growth appearing discontinuous. At 8 weeks (acute setting), substantial remodeling was observed with higher degrees of bone organization characterized by appositional bone growth. The chronic healing, experimental, group yielded bone formation and remodeling, with no indication of non-union after treatment with AIBG. Furthermore, bone growth in the chronic healing group was accompanied by an increased presence of osteons, osteonal canals, and interstitial lamellae. Qualitatively and semiquantitatively, chronic application of AI facilitated complete bridging of the induced non-union defects, while untreated defects or defects treated acutely with AIBG demonstrated a lack of complete bridging at 8 weeks., (© 2024 Orthopaedic Research Society.)

Alport syndrome is an inherited kidney disease, which can lead to glomerulosclerosis and fibrosis, as well as end-stage kidney disease in children and adults. Platelet-derived growth factor-D (PDGF-D) mediates glomerulosclerosis and interstitial fibrosis in various models of kidney disease, prompting investigation of its role in a murine model of Alport syndrome. In vitro, PDGF-D induced proliferation and profibrotic activation of conditionally immortalized human parietal epithelial cells. In Col4a3 -/- mice, a model of Alport syndrome, PDGF-D mRNA and protein were significantly up-regulated compared with non-diseased wild-type mice. To analyze the therapeutic potential of PDGF-D inhibition, Col4a3 -/- mice were treated with a PDGF-D neutralizing antibody. Surprisingly, PDGF-D antibody treatment had no effect on renal function, glomerulosclerosis, fibrosis, or other indices of kidney injury compared with control treatment with unspecific IgG. To characterize the role of PDGF-D in disease development, Col4a3 -/- mice with a constitutive genetic deletion of Pdgfd were generated and analyzed. No difference in pathologic features or kidney function was observed in Col4a3 -/- Pdgfd -/- mice compared with Col4a3 -/- Pdgfd +/+ littermates, confirming the antibody treatment data. Mechanistically, lack of proteolytic PDGF-D activation in Col4a3 -/- mice might explain the lack of effects in vivo. In conclusion, despite its established role in kidney fibrosis, PDGF-D, without further activation, does not mediate the development and progression of Alport syndrome in mice., (Copyright © 2024 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.)

Tendon injury healing is a complex process that involves the participation of a significant number of molecules and cells, including growth factors molecules in a key role. Numerous studies have demonstrated the function of growth factors in tendon healing, and the recent emergence of EV has also provided a new visual field for promoting tendon healing. This review examines the tendon structure, growth, and development, as well as the physiological process of its healing after injury. The review assesses the role of six substances in tendon healing: insulin-like growth factor-I (IGF-I), transforming growth factor β (TGFβ), vascular endothelial growth factor (VEGF), platelet-derived growth factor (PDGF), basic fibroblast growth factor (bFGF), and EV. Different growth factors are active at various stages of healing and exhibit separate physiological activities. IGF-1 is expressed immediately after injury and stimulates the mitosis of various cells while suppressing the response to inflammation. VEGF, which is also active immediately after injury, accelerates local metabolism by promoting vascular network formation and positively impacts the activities of other growth factors. However, VEGF's protracted action could be harmful to tendon healing. PDGF, the earliest discovered cytokine to influence tendon healing, has a powerful cell chemotaxis and promotes cell proliferation, but it can equally accelerate the response to inflammation and relieve local adhesions. Also useful for relieving tendon adhesion is TGF- β, which is active almost during the entire phase of tendon healing. As a powerful active substance, in addition to its participation in the field of cardiovascular and cerebrovascular vessels, tumour and chronic wounds, TGF- β reportedly plays a role in promoting cell proliferation, activating growth factors, and inhibiting inflammatory response during tendon healing., (© 2023 The Authors. International Wound Journal published by Medicalhelplines.com Inc and John Wiley & Sons Ltd.)

Neural stem cells (NSCs) are considered to be prospective replacements for neuronal cell loss as a result of spinal cord injury (SCI). However, the survival and neuronal differentiation of NSCs are strongly affected by the unfavorable microenvironment induced by SCI, which critically impairs their therapeutic ability to treat SCI. Herein, a strategy to fabricate PDGF-MP hydrogel (PDGF-MPH) microspheres (PDGF-MPHM) instead of bulk hydrogels is proposed to dramatically enhance the efficiency of platelet-derived growth factor mimetic peptide (PDGF-MP) in activating its receptor. PDGF-MPHM were fabricated by a piezoelectric ceramic-driven thermal electrospray device, had an average size of 9 μm, and also had the ability to activate the PDGFRβ of NSCs more effectively than PDGF-MPH. In vitro , PDGF-MPHM exerted strong neuroprotective effects by maintaining the proliferation and inhibiting the apoptosis of NSCs in the presence of myelin extracts. In vivo , PDGF-MPHM inhibited M1 macrophage infiltration and extrinsic or intrinsic cells apoptosis on the seventh day after SCI. Eight weeks after SCI, the T10 SCI treatment results showed that PDGF-MPHM + NSCs significantly promoted the survival of NSCs and neuronal differentiation, reduced lesion size, and considerably improved motor function recovery in SCI rats by stimulating axonal regeneration, synapse formation, and angiogenesis in comparison with the NSCs graft group. Therefore, our findings provide insights into the ability of PDGF-MPHM to be a promising therapeutic agent for SCI repair.

Platelet-derived growth factor AA (PDGF-AA) is an important promoter of tissue injury repair and might be a candidate for improving the mechanical properties of repaired tendons. Here, we designed a PDGF-AA-modified poly(lactide-co-glycolide) acid (PLGA) electrospun fibers to promote tendon rehabilitation after injury. In the present study, we grafted PDGF-AA on the surface of PLGA. In structural experiments, we found that the hydrophilicity of PLGA containing PDGF-AA (PLGA-PDGF-AA) increased, but the strength of the material did not change significantly. Moreover, no significant changes in tendon cell proliferation and viability were observed in the PLGA-PDGF-AA treatment compared with the control group. The mouse tendon injury model ( n = 9) experiment illustrated that PLGA-PDGF-AA effectively promoted tendon healing, and we confirmed that PLGA-PDGF-AA promoted collagen synthesis and deposition by immunohistochemistry and RT-PCR. Moreover, the mechanical strength of PLGA-PDGF-AA-treated mouse ( n = 9) tendon tissue was also higher than that of the PLGA-treated group alone. In conclusion, PLGA-PDGF-AA promoted regeneration after tendon injury and serves as a potential adjuvant material for surgical tendon injury repair.

Intracerebral hemorrhage (ICH) is a common and highly disabling or fatal neurological disorder in adults. Recent studies have suggested that the platelet derived growth factor (PDGF) signaling pathway plays an important role in the development of ICH. PDGF is involved in vascular remodeling and can be used as a biomarker of cerebral amyloid angiopathy which is one of the major causes of ICH. PDGF and its receptors are involved in the mechanism of the secondary injury after ICH by affecting the integrity of the blood-brain barrier and inflammatory response. PDGF and its receptors may also participate in the mechanism of repair after ICH by promoting angiogenesis. This article reviews the latest research progress on the involvement of PDGF signaling pathway in the pathophysiology of intracerebral hemorrhage, and introduces the relevant antagonists using PDGFR as the therapeutic target, to provide information for the development of therapeutic options for intracerebral hemorrhage.

Aims: The management of diabetic foot ulcers is a challenging issue due to the pathophysiological background, delay in healing, and prevalence of diabetes. The purpose of this study was to compare the therapeutic effects of the three methods of diabetic wound care: surgical debridement and dressing, dressing with dehydrated amnion powder, and dressing with platelet-derived growth factor gel., Methods: In this multi-arm parallel-group randomized trial, 243 patients with a minimum 4-week medical history of diabetic foot ulcers with Wagner's grades 1 and 2, no infection, and adequate tissue blood flow were randomly assigned to one of three 81-person groups: surgical debridement (the standard method), dehydrated amnion dressing, or platelet-derived growth factor dressing. The follow-up period lasted 12 weeks. The percentage area reduction (PAR) was measured as the final target. SPSS version 25 was used to perform statistical analysis on the data., Results: All three study groups were comparable in terms of the type of ulcer, the area of ulcer, Wagner's grade, the period, and the ulcer's size. The PAR in the surgical debridement, platelet-derived growth factor, and dehydrated amnion groups were 7.4%, 14.8%, and 49.3% in week 4; 20.1%, 35.8%, and 79% in week 6; 43.7%, 56.8%, 86.4% in week 8; and 50%, 61.7%, and 87.6% in weeks 10 and 12, respectively. The observed differences were statistically significant (p < 0.05) over the entire period., Conclusion: The study concluded that dehydrated amnion dressing, when compared to platelet-derived growth factor dressing and surgical debridement, resulted in better-improved healing in diabetic foot ulcer patients., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Background: Angiogenesis is a hallmark of cancer, which is regulated by diverse factors, including long non-coding RNAs (lncRNAS). Our previous study showed that the long non-coding RNA H22954 inhibits tumor growth, albeit whether it is involved in the angiogenesis of cancer re-mains unknown., Objectives: This study aimed to investigate the role of lncRNA H22954 in angiogenesis of acute myeloid leukemia (AML) and the underlying molecular mechanism., Methods: Bioinformatics analysis was conducted to screen the targeted molecule of H22954. Western blot and ELISA analysis detected PDGFA protein expression, and RT-qPCR detected H22954 and PDGFA expression in cell lines and AML samples. Dual-luciferase reporter gene assay and half-life assay were applied to validate the relationship between H22954 and PDGFA. The functional experi-ment was conducted to investigate the role of H22954 in tube formation., Results: Overexpression of H22954 inhibited angiogenesis in mouse xenograft tumors and cultured acute myeloid leukemia (AML) cells. Bioinformatics analysis and luciferase assay revealed that H22954 targeted the 3' untranslated region (UTR) of the platelet-derived growth factor subunit A (PDGFA) gene. In transfected cells, H22954 overexpression reduced PDGFA expression and protein levels. Tube formation was rescued following the addition of exogenous human PDGFA to the con-ditioned medium from cells overexpressing H22954. The expression of H22954 in K562 cells re-duced the half-life of PDGFA mRNA. Furthermore, H22954 expression was inversely correlated with PDGFA expression in patient samples., Conclusion: These findings indicate that H22954 inhibits angiogenesis in AML through the down-regulation of PDGFA expression. Administering recombinant lncRNA H22954 may be a therapeutic approach for patients with AML., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Type 2 diabetes mellitus is a type of metabolic disorder characterized by hyperglycaemia with multiple serious complications, such as diabetic neuropathies, diabetic nephropathy, diabetic retinopathy, and diabetic foot. Platelet-derived growth factors are growth factors that regulate cell growth and division, playing a critical role in diabetes and its harmful complications. This review focused on the cellular mechanism of platelet-derived growth factors and their receptors on diabetes development. Furthermore, we raise some proper therapeutic molecular targets for the treatment of diabetes and its complications.

Recently, platelet-rich plasma (PRP) has received attention as a treatment for patients with osteoarthritis of the knee (OAK), a chronic degenerative disease, to bridge the gap between conservative and surgical treatments. Here, we investigated the differences in the humoral factors present in two types of PRP purified using the Autologous Protein Solution (APS) kit (group Z; leucocyte-rich PRP) or the Cellaid Serum Collection Set P type (group J; leucocyte-poor [LP]-PRP). Differences in humoral factors between healthy subjects (n = 10) and OAK patients (n = 12; group Z = 6, group J = 6), and the relationship between humoral factors and clinical outcome scores were investigated. Both anti-inflammatory and inflammatory cytokines were highly enriched in APS. The concentrations of tumour necrosis factor (TNF)-α, platelet-derived growth factor, fibroblast growth factor, soluble TNF-receptor 2, soluble Fas and transforming growth factor-β1 were higher in group Z, while the total amounts were higher in group J. The concentration of interleukin-1 receptor antagonist was positively correlated with the magnitude of change in the clinical outcome score and may contribute to improving knee-joint function. This is the first description of the humoral factors in APS and LP-PRP prepared from healthy subjects or OAK patients of Asian descent.

Therapies that target scar formation after myocardial infarction (MI) could prevent ensuing heart failure or death from ventricular arrhythmias. We have previously shown that recombinant human platelet-derived growth factor-AB (rhPDGF-AB) improves cardiac function in a rodent model of MI. To progress clinical translation, we evaluated rhPDGF-AB treatment in a clinically relevant porcine model of myocardial ischemia-reperfusion. Thirty-six pigs were randomized to sham procedure or balloon occlusion of the proximal left anterior descending coronary artery with 7-day intravenous infusion of rhPDGF-AB or vehicle. One month after MI, rhPDGF-AB improved survival by 40% compared with vehicle, and cardiac magnetic resonance imaging showed left ventricular (LV) ejection fraction improved by 11.5%, driven by reduced LV end-systolic volumes. Pressure volume loop analyses revealed improved myocardial contractility and energetics after rhPDGF-AB treatment with minimal effect on ventricular compliance. rhPDGF-AB enhanced angiogenesis and increased scar anisotropy (high fiber alignment) without affecting overall scar size or stiffness. rhPDGF-AB reduced inducible ventricular tachycardia by decreasing heterogeneity of the ventricular scar that provides a substrate for reentrant circuits. In summary, we demonstrated that rhPDGF-AB promotes post-MI cardiac wound repair by altering the mechanics of the infarct scar, resulting in robust cardiac functional improvement, decreased ventricular arrhythmias, and improved survival. Our findings suggest a strong translational potential for rhPDGF-AB as an adjunct to current MI treatment and possibly to modulate scar in other organs., (Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.)

Regenerative paradigms exhibit nerve dependency, including regeneration of the mouse digit tip and salamander limb. Denervation impairs regeneration and produces morphological aberrancy in these contexts, but the direct effect of innervation on the stem and progenitor cells enacting these processes is unknown. We devised a model to examine nerve dependency of the mouse skeletal stem cell (mSSC), the progenitor responsible for skeletal development and repair. We show that after inferior alveolar denervation, mandibular bone repair is compromised because of functional defects in mSSCs. We present mSSC reliance on paracrine factors secreted by Schwann cells as the underlying mechanism, with partial rescue of the denervated phenotype by Schwann cell transplantation and by Schwann-derived growth factors. This work sheds light on the nerve dependency of mSSCs and has implications for clinical treatment of mandibular defects., (Copyright © 2019 The Author(s). Published by Elsevier Inc. All rights reserved.)

Objectives: This study aims to investigate the potential use and histological effects of the local administration of platelet-derived growth factor (PDGF) in the repair of full-thickness osteochondral defects in articular cartilage in an animal model., Materials and Methods: Twenty-four adolescent 18-week-old New Zealand White rabbits with an average weight of 2500 g (range, 1600 g to 3200 g) were used in the study. The rabbits were randomly divided into three groups (n=8) as the control group (group A) and two experimental groups (groups B and C). Defects of cylindrical full-thickness (3.5 mm wide, 4 mm deep) were created in the weight-bearing area of the right knee medial femoral condyles. In group A, the defect was left empty. In group B, the defect was filled with a collagen sponge. In group C, the defect was filled with a collagen sponge impregnated with PDGF. All rabbits were followed-up for 12 weeks. Right knee medial femoral condyles were used for macroscopic and histological analyses., Results: At macroscopic level, the repair tissue was similar to normal adjacent cartilage at 12 weeks in group C. The surface of the repair tissue in group C was smoother and more regular compared to groups A and B. The total histological score of defects in group C was statistically significantly superior compared to groups A and B (p<0.05). Matrix staining and immunostaining of collagen type 2 were stronger in group C compared to the other groups, indicating the presence of a tissue similar to a normal cartilage., Conclusion: Platelet-derived growth factor can induce repair in full-thickness defects of articular cartilage in an animal model. Thus, this study demonstrates the potential use of PDGF for full-thickness osteochondral defects.

Reconstruction of the diabetic Charcot foot can be a challenge even for the most experienced foot and ankle surgeon. The first portion of this article discusses the preoperative evaluation with an emphasis on factors that can be modified before surgical reconstruction to help optimize surgical results. The second portion of the article focuses on intraoperative methods and techniques to help improve postoperative outcomes. Surgeons should strive to provide high-quality, cost-effective care by optimizing patient selection and perioperative care. Objective measures of patient outcomes will become increasingly important with the transition from volume-based to value-based care., (Copyright © 2019 Elsevier Inc. All rights reserved.)

The management of rotator cuff tears continues to prove challenging for orthopaedic surgeons. Such tears affect most age groups and can lead to significant morbidity in patients. The aetiology of these tears is likely to be multifactorial; however, an understanding of the mechanisms involved is still under review. Despite advancements in surgical operative techniques and the materials used, post-operative recurrence rates after surgical repair remain high. A growing area of research surrounds biological adjuncts used to improve the healing potential of the repaired tissues. This review of recent publications focuses on the strengths and limitations of using stem cells and growth factors in rotator cuff repair.

In this study, we prepared the platelet-derived growth factor-containing porous microspheres modified with heparin (PDGF/Hep-PMSs) and investigated their anti-inflammatory and tendon healing effects on rotator cuff (RC) tendinitis rabbit model. PDGF/Hep-PMSs suppressed the mRNA levels of six pro-inflammatory cytokines (i.e., MMP-3, MMP-13, COX-2, ADAMTS-5, IL-6, and TNF-α) in inflamed tenocytes. Long-term local delivery of PDGF/Hep-PMSs into tendon tissues of RC tendinitis decreased the mRNA levels of six pro-inflammatory cytokines and increased the mRNA levels of anti-inflammatory cytokines including IL-4, IL-10, and IL-13. Anti-inflammatory effects of PDGF/Hep-PMSs might have contributed to enhance the collagen content, tenogenic markers, stiffness, and tensile strength of tendons, eventually leading to tendon restoration. Our findings suggest that the long-term local PDGF delivery of PDGF/Hep-PMSs have a great potential to enhance tendon healing of RC tendinitis by suppressing inflammation responses., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Purpose of Review: The development of therapeutics that target anabolic pathways involved in skeletogenesis is of great importance with regard to disease resulting in bone loss, or in cases of impaired bone repair. This review aims to summarize recent developments in this area., Recent Findings: A greater understanding of how drugs that modulate signaling pathways involved in skeletogenesis exert their efficacy, and the molecular mechanisms resulting in bone formation has led to novel pharmacological bone repair strategies. Furthermore, crosstalk between pathways and molecules has suggested signaling synergies that may be exploited for enhanced tissue formation. The sequential pharmacological stimulation of the molecular cascades resulting in tissue repair is a promising strategy for the treatment of bone fractures. It is proposed that a therapeutic strategy which mimics the natural cascade of events observed during fracture repair may be achieved through temporal targeting of tissue repair pathways.

Chronic low back pain is a critical health problem and a leading cause of disability in aging populations. A major cause of low back pain is considered to be the degeneration of the intervertebral disc (IVD). Recent advances in therapeutics, particularly cell and tissue engineering, offer potential methods for inhibiting or reversing IVD degeneration, which have previously been impossible. The use of growth factors is under serious consideration as a potential therapy to enhance IVD tissue regeneration. We reviewed the role of chosen prototypical growth factors and growth factor combinations that have the capacity to improve IVD restoration. A number of growth factors have demonstrated potential to modulate the anabolic and anticatabolic effects in both in vitro and animal studies of IVD tissue engineering. Members of the transforming growth factor-β superfamily, IGF-1, GDF-5, BMP-2, BMP-7, and platelet-derived growth factor have all been investigated as possible therapeutic options for IVD regeneration. The role of growth factors in IVD tissue engineering appears promising; however, further extensive research is needed at both basic science and clinical levels before its application is appropriate for clinical use.

Arthrodesis of the ankle or foot is a common procedure for chronic pain and disability. Nonunion remains a prevalent complication among arthrodesis procedures. Some patients present with an inherent risk of developing a nonunion. Allograft biologics have gained popularity in an effort to reduce complications such as nonunion. Various biologics bring unique properties while maintaining a singular purpose. Platelet-derived growth factor (PDGF) may be introduced into a fusion site to facilitate healthy bony consolidation. The purpose of this article is to review the benefits and modalities of PDGF and how it can improve patient outcomes in ankle and hindfoot fusions., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Neonatal chronic lung disease (nCLD) affects a significant number of neonates receiving mechanical ventilation with oxygen-rich gas (MV-O 2 ). Regardless, the primary molecular driver of the disease remains elusive. We discover significant enrichment for SNPs in the PDGF-Rα gene in preterms with nCLD and directly test the effect of PDGF-Rα haploinsufficiency on the development of nCLD using a preclinical mouse model of MV-O 2 In the context of MV-O 2 , attenuated PDGF signaling independently contributes to defective septation and endothelial cell apoptosis stemming from a PDGF-Rα-dependent reduction in lung VEGF-A. TGF-β contributes to the PDGF-Rα-dependent decrease in myofibroblast function. Remarkably, endotracheal treatment with exogenous PDGF-A rescues both the lung defects in haploinsufficient mice undergoing MV-O 2 Overall, our results establish attenuated PDGF signaling as an important driver of nCLD pathology with provision of PDGF-A as a protective strategy for newborns undergoing MV-O 2 ., (© 2017 Helmholtz Zentrum München Published under the terms of the CC BY 4.0 license.)

Age-related macular degeneration (AMD) is considered one of the main causes of severe vision loss in older adults. The neovascular form (nAMD) is an advanced stage, which is responsible for the most severe vision loss. Vascular endothelial growth factor (VEGF) is at present the main factor that leads to the development of a neovascular membrane and the increased leakage from the membrane to the retina. At present, anti-VEGF therapy is the only treatment that achieves vision gains in many patients and halts progression in most of them. VEGF blockade can be achieved with several molecules and various treatment regimens, which have been studied with excellent results. Unfortunately, real-world data has shown to be far less efficacious than clinical trials. This gap between clinical trials and real-world results is an unmet medical need that supports the necessity of new treatment modalities for nAMD. Of the various treatments being studied, anti-VEGFs of higher efficacy and longer durability are those more advanced in their development. Brolucizumab and abicipar pegol are 2 new anti-VEGF drugs that had positive results in phase 2 studies and are being tested in phase 3 trials at present. Other promising therapies are antiangiopoietin 2 molecules, which are in phase 2 development. At earlier stages of development but with promising results are squalamine, anti-VEGF-C and -D, and gene therapy. The future will give retina specialists a broad armamentarium with which patients may achieve high visual gains for the long term with a low treatment burden., (Copyright 2017 Asia-Pacific Academy of Ophthalmology.)

Background: Patients who receive laser treatments may experience transient erythema, edema, and crusts for several days. Although a variety of growth factor-containing creams for promoting recovery after laser treatment are available, evidence for their efficacy remains insufficient., Aims: We performed a randomized controlled split-face study to assess the effects of a multigrowth factor (MGF)-containing cream on patients recovering from laser treatment., Materials and Methods: Twenty patients underwent treatment using an ablative fractional laser and were randomized with respect to the side of the face treated with an MGF-containing cream or control cream. We measured post-treatment erythema and pigmentation using the erythema and melanin indices, respectively, and evaluated the total area of microcrusts with dermoscopy. Additionally, patient satisfaction levels and global improvement scores were assessed., Results: We found that the area of microcrusts was significantly smaller in the MGF-treated regions. Global improvement scores for post-treatment edema and wrinkles were also significantly higher for MGF cream-treated sides than for the control sides., Conclusion: The MGF cream-treated regions showed a more rapid recovery from crusts and edema. Thus, the use of an MGF-containing cream after laser treatment can effectively reduce recovery time., (© 2016 Wiley Periodicals, Inc.)

Defective vascular and cardiomyocyte function are implicated in the development and progression of both heart failure with reduced and preserved ejection fraction. Any treatment option that augments these myocardial processes may therefore be of significant value. The platelet-derived growth factor (PDGF) family is involved in a wide range of growth processes and plays a key role in both regulating angiogenesis and mesenchymal cell development. Thus, PDGF may serve as a potent therapy for heart failure. While numerous animal studies have demonstrated beneficial cardiovascular effects of growth factor therapy, promising laboratory data has not yet translated to effective therapies. In this review, we outline the biological role of PDGF and summarize previous studies that have focused on the cardiovascular effects of normal PDGF signaling, administration of PDGF, and the effects of PDGF on stem cell therapy.

Objective: This study aims to observe encephaledema and cell apoptosis in rats following subarachnoid hemorrhage (SAH) and to explore the mechanism of platelet-derived growth factor receptor (PDGFR) in the development of early brain injury (EBI)., Methods: Adult and male Sprague-Dawley rats were randomly divided into 4 groups: sham operation, SAH, SAH + imatinib, and SAH + platelet-derived growth factor-BB (PDGF-BB). SAH model was established using intravascular silk puncture of the internal carotid artery crotch. The SAH + imatinib group was treated with intraperitoneal injection of imatinib 1 hour before establishing the model. The SAH + PDGF-BB group was administered with intracerebroventricular injection of PDGF-BB 1 hour before establishing the model. The mortality, encephaledema, and nerve functional scoring were observed after 24 hours in all groups. The expression of caspase-3 in hippocampus was tested by reverse transcription polymerase chain reaction and Western blotting., Results: Mortality and encephaledema were the highest in the SAH + PDGF-BB group, which were alleviated when the rats were injected with imatinib (P < .01)., Conclusion: PDGFR may participate in the pathogenesis of EBI following SAH. The antagonist of PDGFR, imatinib, can reduce brain damage to some degree., (Copyright © 2016 National Stroke Association. Published by Elsevier Inc. All rights reserved.)

Purpose: An arthroscopic procedure for the treatment of osteochondral defects using platelet-derived growth factor (PDGF) carried out in a matrix of tricalcium phosphate was developed. This prospective, case-series-based study was designed to evaluate the safety and clinical utility of this procedure., Methods: Patients with an isolated osteochondral defect larger than 5 mm long, 3 mm wide, and 5 mm deep and smaller than 30 mm long, 25 mm wide, or 20 mm deep were considered for enrolment. Only patients with chronic lesions were enroled. Arthroscopic debridement was followed by the placement of recombinant human PDGF in a matrix of tricalcium phosphate. The Ankle Osteoarthritis Scale (AOS), visual analogue scale (VAS) for pain, and SF-36 questionnaires were administered at 0, 2, 6, 12, and 24 weeks. Magnetic resonance imaging (MRI) and computed tomography (CT) scans were taken before and after surgery., Results: Five patients were ultimately enroled in this proof-of-concept trial. All outcome measures demonstrated marked improvement from baseline to final follow-up: The mean weight bearing VAS pain score improved by 49%, and the mean AOS functional score improved by 28%. Bone healing was seen on CT, and reduction in oedema signal was seen on MRI., Conclusion: This new procedure may offer a promising alternative for the treatment of osteochondral defects. Further high-quality studies are needed to confirm these results and to analyse the long-term effects of the procedure. The clinical relevance of this study is that the procedure may provide a less invasive option with improved bone healing compared to standard techniques ., Level of Evidence: IV.

Exploration into the molecular aspects of the healing process has led to the development of autologous and recombinant biologic agents. These products, collectively known as orthobiologics, have the potential to optimize favorable outcomes with respect to bone and soft-tissue restoration and to maximize the natural healing response. These orthobiologics include platelet-derived growth factor, bone morphogenetic proteins, and platelet-rich plasma. Although the usefulness of these growth factors is well described in various fields of surgery, few data exist to support or oppose the specific application of growth factors in foot and ankle surgery.

Regenerative endodontic treatment has provided a treatment option that aims to allow root maturation. The present report describes the regenerative endodontic treatment of a necrotic, immature molar by using recombinant human platelet-derived growth factor (rhPDGF-BB) and shows the continued root maturation in the tooth with arrested root development. A regenerative endodontic procedure that used a growth factor was performed for a necrotic molar with arrested root formation in a 20-year-old patient. Thorough disinfection by using mechanical instrumentation and copious irrigation of antimicrobial agents as well as intracanal medication with calcium hydroxide was performed throughout the first 2 appointments. At the third appointment, the root canals were irrigated with an antimicrobial solution and 17% EDTA, and bleeding was evoked by passing sterile paper points beyond the apex in each canal. Small pieces of a collagen membrane saturated with rhPDGF-BB solution from GEM 21S were packed into each canal. Mineral trioxide aggregate was placed, and Cavit and composite resin were used to restore the tooth. Complete root maturation and resolution of a periapical radiolucency were observed at the 15-month follow-up. The present report presents a regenerative endodontic procedure that uses rhPDGF-BB for a necrotic molar with arrested root development. The finding of continued root development in the present case suggests that regenerative endodontic treatment may be able to resume the root maturation process in teeth with arrested root formation. Further clinical studies are required to investigate the efficacy of rhPDGF-BB in regenerative endodontic treatment., (Copyright © 2016 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.)

The objective of the present real-time in vivo experiment was to assess guided bone regeneration (GBR) in standardized calvarial defects using particulate graft material (Bio-Oss) and β-tricalcium phosphate (β-TCP) with adjunct recombinant human platelet-derived growth factor (rhPDGF) therapy. Eighteen female Sprague-Dawley rats with a mean age and weight of 8 ± 0.53 weeks and 250 ± 0.49 g, respectively, were used. Following surgical exposure, a full-thickness standardized calvarial defect was created on the parietal bone using a trephine drill with an outer diameter of 4.6 mm. For treatment, rats were randomly divided into three groups (six rats per group): (1) control; (2) rhPDGF + Bio-Oss, and (3) rhPDGF + β-TCP. Volume of newly formed bone (NFB), bone mineral density (BMD) of NFB, volume of remnant bone particles, and BMD of remnant bone particles were assessed using in vivo microcomputed tomography. Measurements were made at baseline and at 2, 4, 6, and 10 weeks after the surgical procedures. At 10 weeks, all animals were sacrificed and calvarial tissues were assessed histologically. In the control group, a significant increase in BMD of NFB was observed at 6 weeks (mean ± standard deviation [SD], 0.32 ± 0.002 g/mm(3)) (P < .01) from baseline, and the defect did not regenerate completely. In the rhPDGF + Bio-Oss group, mean ± SD volume (2.40 ± 0.25 mm(3)) (P < .01) and BMD (0.13 ± 0.01 g/mm(3)) of NFB significantly increased at 4 weeks and 6 weeks, respectively, from baseline (P < .001). In the rhPDGF + β-TCP group, mean ± SD volume (2.01 ± 0.7 mm(3)) and BMD (0.12 ± 0.02 g/mm(3)) of NFB significantly increased at 4 weeks from baseline (P < .01). In the rhPDGF + Bio-Oss and rhPDGF + β-TCP groups, mean ± SD BMD of remnant bone particles (0.31 ± 0.11 g/mm(3) and 0.23 ± 0.01 g/mm(3)) showed significant reduction at 6 and 10 weeks, respectively, compared with baseline values (1.12 ± 0.06 g/mm(3) and 0.92 ± 0.01 g/mm(3), respectively) (P < .001). Histologic results at 10 weeks showed NBF in the rhPDGF + Bio-Oss and rhPDGF + β-TCP groups. In real time assessment, when rhPDGF was added to β-TCP, BMD and bone hardness significantly increased compared with the other two groups.

The use of blood derivatives represents an alternative therapeutic approach that is gaining interest in regenerative medicine due to its potential to stimulate and accelerate tissue healing. Autologous serum eye drops and platelet-enriched plasma eye drops are being used in the treatment of different ophthalmological disorders. In this review, we summarize the different blood-derived formulations used in the treatment and care of ocular surface disorders. The biological basis and use of autologous serum and plasma rich in growth factors are deeply evaluated as well as the challenges to be addressed in the future in this new generation of blood-derived therapies., (© 2015 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.)

Objective: This study sought to compare the efficacy of topical platelet derived growth factor (Regranex, Smith and Nephew, London, UK) (test group) to placebo (control group) in treating diabetic foot ulcers. All subjects had a short leg walking cast with a window fashioned in the cast over the site of the ulcer., Methods: Forty-six subjects were randomized (double-blind) 1:1 to the test or control group and treated for up to 4 months. Subjects had Wagner grade I ulcers with wound area of 1 cm2 to 16 cm2 without severe peripheral arterial disease, osteomyelitis, or any infection requiring antibiotics. Study medication was applied daily and casts changed approximately every 14 days., Results: Of the 46 subjects randomized, 38 either healed or completed 16 weeks of therapy without healing. Eight subjects dropped out prior to 16 weeks. Based on intention-to-treat, 12 of 23 (52%) test group subjects healed before 16 weeks compared to 13 of 23 (57%) control group subjects (not significant). Regression analysis demonstrated that slower healing was associated with larger initial wound size (hazard radio [HR] = 0.997, 95% confidence interval [CI]: 0.995-1.00, P = 0.028) and excessive wound drainage (HR = 0.346, 95% CI: 0.126-0.948, P = 0.039). Excluding the patients who dropped out, 25 of 38 (66%) subjects healed by 4 months. Three additional subjects healed with casts that were worn longer than 4 months, for an overall rate of 74% at 9 months. Five subjects developed cast burns, and 3 patients required amputation., Conclusion: Topical platelet derived growth factor does not appear to significantly improve healing of Wagner grade I diabetic foot ulcers that are treated by offloading with a short leg walking cast. Excellent healing rates may be achieved with casting alone.

Background: Recombinant human platelet-derived growth factor BB (rhPDGF-BB) combined with an osteoconductive scaffold (β-TCP) has been demonstrated to increase bone formation, but rhPDGF-BB has not been studied in human fractures. The purpose of this study was to evaluate the safety and potential use of locally administered rhPDGF-BB/β-TCP (Augment®) in acute wrist fractures., Methods: Forty patients with unstable distal radial fracture were randomized to closed reduction and external fixation alone (n = 20) or combined with injection of rhPDGF-BB/β-TCP (Augment®) into the fracture (n = 20). All patients were followed for 24 weeks. Outcome was based on adverse events, fracture displacement on radiographs, fracture healing, range of motion, grip strength, pain, and the disability of the arm, shoulder and hand (DASH) score., Results: There were no serious adverse events in the study, but the pin tract infection rate was significantly lower in the Augment® group. There was no difference between the groups in fracture healing time, based on number of healed cortices or fracture displacement. The Augment® group had an early temporary significant decrease in wrist flexion, but no difference in range of motion at 24 weeks. There were no differences between the two treatment groups for any other outcome variables., Conclusion: rhPDGF-BB/β-TCP (Augment®) is safe and convenient for local administration into wrist fractures. In this pilot study, we could not detect any reduced healing time in the Augment® group although potential efficacy should be addressed in larger studies., Clinical Trial Registration Number: The clinical trial registration number for the study protocol is BMPI-2014-02-E.

Purpose: To evaluate the potential of heterologous platelet-rich plasma (PRP) gel for surgical skin wound healing in rabbits., Methods: Blood from a single healthy dog was used for PRP production, with calcium gluconate added to the PRP to form the gel. Two surgical excisions, one to the right and the other to the left of the dorsal midline, were made in six rabbits. One side was randomly allocated to topical application of a physiological solution, and the other was allocated to treatment with heterologous PRP gel. Clinical assessments (weight, pain sensitivity, coloring, edema, hyperemia, exudation, crust, and granulation) and morphometric evaluations were performed 0, 3, 7, 10, 14, and 17 days postoperatively. Histological analysis was performed on the 17th day., Results: With the exception of the presence of a crust at day 10, clinical variables did not differ significantly between the experimental groups. In both the control and PRP-treated groups, differences were identified when comparing time-points in terms of wound area reduction. Histological results indicated no significant differences between the control group and the PRP-treated group., Conclusion: Heterologous platelet-rich plasma gel promoted dermal wound healing in rabbits with no adverse effects.

Fibrosis is one of the leading causes of morbidity and mortality in the Western world. This disorder is characterised by an abnormal and increased rate of fibroblast proliferation and by an excessive deposition of connective tissue. The key player in fibrosis is the myofibroblast. Fibrosis leads to loss of organ structure and, eventually, to decrease in organ function. To date, there are hardly any effective therapies for the treatment of patients with fibrosis. Pirfenidone targets the myofibroblast and is effective in the treatment of idiopathic pulmonary fibrosis. Tyrosine kinase inhibitors are effective for the treatment of patients with some forms of systemic sclerosis. Here we describe various novel therapeutic targets, such as transforming growth factor beta (TGF-β), platelet-derived growth factor (PDGF), interleukin-13 (IL-13), lysyloxidase-2 and macrophage-fibroblast interactions. These new therapies are currently under investigation in pre-clinical and clinical studies.

Electrospun nanofibers have been extensively used in growth factor delivery and regenerative medicine due to many advantages including large surface area to volume ratio, high porosity, excellent loading capacity, ease of access and cost effectiveness. Their relatively large surface area is helpful for cell adhesion and growth factor loading, while storage and release of growth factor are essential to guide cellular behaviors and tissue formation and organization. In bone tissue engineering, growth factors are expected to transmit signals that stimulate cellular proliferation, migration, differentiation, metabolism, apoptosis and extracellular matrix (ECM) deposition. Bolus administration is not always an effective method for the delivery of growth factors because of their rapid diffusion from the target site and quick deactivation. Therefore, the integration of controlled release strategy within electrospun nanofibers can provide protection for growth factors against in vivo degradation, and can manipulate desired signal at an effective level with extended duration in local microenvironment to support tissue regeneration and repair which normally takes a much longer time. In this review, we provide an overview of growth factor delivery using biomimetic electrospun nanofiber scaffolds in bone tissue engineering. It begins with a brief introduction of different kinds of polymers that were used in electrospinning and their applications in bone tissue engineering. The review further focuses on the nanofiber-based growth factor delivery and summarizes the strategies of growth factors loading on the nanofiber scaffolds for bone tissue engineering applications. The perspectives on future challenges in this area are also pointed out.

Autoplasma enriched with platelet derived growth factor (AET) is a technology that is included in the scope of regenerative medicine. The main active component of AET is biologically active substance - of growth factors, cytokines and chemokines involved in cell growth, proliferation and cell differentiation in accordance with the tissue species specifity. This article presents information on ingredients of autoplasma, classification of AET preparations; the possible mechanisms of action are discussed, and the results of pre-clinical and clinical trials of AET in various diseases, including erectile dysfunction, are also reviewed.

Inflammation of the spinal cord after traumatic spinal cord injury (SCI) leads to destruction of healthy tissue. This "secondary degeneration" is more damaging than the initial physical damage and is the major contributor to permanent loss of functions. In our previous study, we showed that combined delivery of two growth factors, vascular endothelial growth factor and platelet-derived growth factor, significantly reduced secondary degeneration after hemisection injury of the spinal cord in the rat. Growth factor treatment reduced the size of the lesion cavity at 30 days, compared to control animals, and further reduced the cavity at 90 days in treated animals, whereas in control animals the lesion cavity continued to increase in size. Growth factor treatment also reduced astrogliosis and reduced macroglia/macrophage activation around the injury site. Treatment with individual growth factors alone had similar effects to control treatments. The present study investigated whether growth factor treatment would improve locomotor behavior after spinal contusion injury, a more relevant pre-clinical model of SCI. The growth factors were delivered for the first 7 days to the injury site by osmotic minipump. Locomotor behavior was monitored at 1-28 days after injury using the Basso, Beattie and Bresnahan (BBB) score and at 30 days using automated gait analysis. Treated animals had BBB scores of 18; control animals scored 10. Treated animals had significantly reduced lesion cavities and reduced macroglia/macrophage activation around the injury site. We conclude that growth factor treatment preserved spinal cord tissues after contusion injury, thereby allowing functional recovery. This treatment has the potential to significantly reduce the severity of human spinal cord injuries.

Background/aim: The aim of the present study was to evaluate the safety and the clinical outcome of platelet-rich plasma for the treatment of teno-desmic injures in competition horses., Patients and Methods: From January 2009 to December 2011, 150 sport horses suffering from teno-desmic injuries were treated with no-gelled platelet-concentrate., Results: No horse showed any major adverse reaction as a result of the procedure. Full healing was obtained for 81% of the horses. Twelve percent had clinical improvement and only 7% a failure. Eight percent of cases of relapse were observed. No statistically significant correlation existed between clinical outcome and the area of the lesion. A statistically significant correlation existed between the clinical outcome and the age of the horse., Conclusion: Treatment with platelet-derived growth factors leads to the formation of a tendon with normal morphology and functionality, which translate in the resumption of the agonistic activity for the horses we treated., (Copyright © 2014 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.)

Objective: Recombinant human platelet-derived growth factor (rhPDGF) is used topically in the treatment of diabetic lower-extremity ulcers. There have been few meta-analyses of the efficacy of rhPDGF in this treatment context. The aim of this study was to perform an updated systematic review and meta-analysis to assess the clinical efficacy of rhPDGF in the treatment of diabetic lower-extremity ulcers., Methods: We searched the MEDLINE, Cochrane Library, EMBASE and Web of Knowledge databases up to April 30, 2014. Studies were identified and selected, and data were extracted by two independent reviewers. The primary efficacy outcome was complete healing rate. Adverse events were also assessed. The studies were evaluated for quality and publication bias., Results: A total of 6 randomized controlled trials including 992 patients were selected from 173 identified studies. The studies compared rhPDGF treatment in the context of standard of care (SOC) to placebo or SOC alone. In the absence of study heterogeneity, a fixed-effects model was performed, and the combined odds ratio (OR) indicated a significantly greater complete healing rate in patients treated with rhPDGF compared to placebo or SOC alone. The ORs ranged from 0.58 to 2.77, with a combined OR of 1.53 (95% CI = 1.14 to 2.04, p = 0.004). A sensitivity analysis (leave-one-out method) indicated good study reliability, and a funnel plot with Egger test showed no publication bias., Conclusion: These results indicate that rhPDGF is efficacious in the treatment of diabetic lower-extremity ulcers., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Wound healing is a complex and dynamic biological process that involves the coordinated efforts of multiple cell types and is executed and regulated by numerous growth factors and cytokines. There has been a drive in the past two decades to study the therapeutic effects of various growth factors in the clinical management of nonhealing wounds (e.g., pressure ulcers, chronic venous ulcers, diabetic foot ulcers). For this review, we conducted an online search of Medline/PubMed and critically analyzed the literature regarding the role of growth factors and cytokines in the management of these wounds. We focused on currently approved therapies, emerging therapies, and future research possibilities. In this review, we discuss four growth factors and cytokines currently being used on and off label for the healing of wounds. These include granulocyte-macrophage colony-stimulating factor, platelet-derived growth factor, vascular endothelial growth factor, and basic fibroblast growth factor. While the clinical results of using growth factors and cytokines are encouraging, many studies involved a small sample size and are disparate in measured endpoints. Therefore, further research is required to provide definitive evidence of efficacy., (© 2014 by the Wound Healing Society.)

Background: This work evaluates the effect of adding platelet-derived growth factor to autologous adipose tissue grafts in the treatment of human immunodeficiency virus facial lipoatrophy by means of objective measurements., Methods: This is a randomized clinical trial conducted at the Hospital Clinic of Barcelona. Patients with facial human immunodeficiency virus atrophy were randomized into two groups, one treated with autologous fat injection (group A), and another treated with autologous fat injection with plasma rich in growth factors (group B). Before the treatment, structural changes were identified in facial soft tissue by means of computed tomography, and clinical changes were also assessed by means of photographic records. Posttreatment assessments were repeated after 2 and 12 months to compare the results. Posttreatment complications were recorded., Results: Forty-nine patients (33 men and 16 women), with a mean age of 46 years, participated in the study. In both groups, there was a statistically significant average increase of volume in the facial area measured by computed tomography between the baseline and the 2- and 12-month posttreatment assessments. All cases showed an improvement of the clinical facial atrophy grade after treatment, which was statistically significant. This improvement was related to a statistically significant fat volume increase measured by means of computed tomography. There was no difference in the volume gain between both groups. No major complications were observed., Conclusions: Fat grafting is a safe, effective, and durable treatment for human immunodeficiency virus facial atrophy. The results of this study show that it is not necessary to add plasma rich in growth factors to the adipose tissue graft to get a better result., Clinical Question/level of Evidence: Therapeutic, II.

The tropical diabetes hand syndrome is a complication affecting patients with diabetes mellitus in the tropics, and consists of localized cellulitis, swelling and ulceration of the hands which may progress to fulminant sepsis and gangrene of the whole limb. It is associated with a poor outcome. We report a 32 year old woman with tropical diabetes hand infection with autoamputation of the digits, review the relevant literature, and highlight the need for prevention and early hospital presentation in diabetics with hand infection, in order to prevent potentially crippling or fatal complications.