Growth Factors In Wound Healing Research Articles

Endothelial response boosted by platelet lysate: The involvement of calcium toolkit

Wound repair is a dynamic process during which crucial signaling pathways are regulated by growth factors and cytokines released by several kinds of cells directly involved in the healing process. However, the limited applications and heterogeneous clinical results of single growth factors in wound healing encouraged the use of a mixture of bioactive molecules such as platelet derivatives for best results in wound repair. An interesting platelet derivative, obtained from blood samples, is platelet lysate (PL), which has shown potential clinical application. PL is obtained from freezing and thawing of platelet-enriched blood samples. Intracellular calcium (Ca2+) signals play a central role in the control of endothelial cell survival, proliferation, motility, and differentiation. We investigated the role of Ca2+ signaling in the PL-driven endothelial healing process. In our experiments, the functional significance of Ca2+ signaling machinery was highlighted performing the scratch wound assay in presence of different inhibitors or specific RNAi. We also pointed out that the PL-induced generation of intracellular ROS (reactive oxygen species) via NOX4 (NADPH oxidase 4) is necessary for the activation of TRPM2 and the resulting Ca2+ entry from the extracellular space. This is the first report of the mechanism of wound repair in an endothelial cell model boosted by the PL-induced regulation of [Ca2+]i.

WOUND HEALING CONCEPTS: CONTEMPORARY PRACTICES AND FUTURE PERSPECTIVES

The advancements in the development of wound dressings have seen tremendous growth in the past few decades. Wound healing approach has majorly shifted from dry healing to moist healing. There has been a significant advancement in our understanding of the underlying physiology involved in wound healing and the associated systemic factors having a direct or indirect influence on the healing. This has resulted in the development of wound dressings designed to treat specific types of wounds. The present review discusses the physiology of wound healing, followed by different factors that contribute to healing. The advancements in wound dressings with their merits and limitations, newer approaches in wound care i.e., hyperbaric oxygen, negative pressure therapy, skin substitutes and role of growth factors in wound healing, have been highlighted. In addition, more recent approaches for effective wound care like smart devices with sensing, reporting and responding functions are discussed.

Endothelial response boosted by platelet lysate: the involvement of calcium toolkit.

Wound repair is a dynamic process during which crucial signaling pathways are regulated by growth factors and cytokines released by several kinds of cells directly involved in the healing process. However, the limited applications and heterogeneous clinical results of single growth factors in wound healing encouraged the use of a mixture of bioactive molecules such as platelet derivatives for best results in wound repair. An interesting platelet derivative, obtained from blood samples, is platelet lysate (PL), which has shown potential clinical application. PL is obtained from freezing and thawing of platelet-enriched blood samples. Intracellular calcium (Ca2+) signals play a central role in the control of endothelial cell survival, proliferation, motility, and differentiation. We investigated the role of Ca2+ signaling in the PL-driven endothelial healing process. In our experiments, the functional significance of Ca2+ signaling machinery was highlighted performing the scratch wound assay in presence of different inhibitors or specific RNAi. We also pointed out that the PL-induced generation of intracellular ROS (reactive oxygen species) via NOX4 (NADPH oxidase 4) is necessary for the activation of TRPM2 and the resulting Ca2+ entry from the extracellular space. This is the first report of the mechanism of wound repair in an endothelial cell model boosted by the PL-induced regulation of [Ca2+]i.

Functionalising Collagen-Based Scaffolds With Platelet-Rich Plasma for Enhanced Skin Wound Healing Potential.

Porous collagen-glycosaminoglycan (collagen-GAG) scaffolds have shown promising clinical results for wound healing; however, these scaffolds do not replace the dermal and epidermal layer simultaneously and rely on local endogenous signaling to direct healing. Functionalizing collagen-GAG scaffolds with signaling factors, and/or additional matrix molecules, could help overcome these challenges. An ideal candidate for this is platelet-rich plasma (PRP) as it is a natural reservoir of growth factors, can be activated to form a fibrin gel, and is available intraoperatively. We tested the factors released from PRP (PRPr) and found that at specific concentrations, PRPr enhanced cell proliferation and migration and induced angiogenesis to a greater extent than fetal bovine serum (FBS) controls. This motivated us to develop a strategy to successfully incorporate PRP homogeneously within the pores of the collagen-GAG scaffolds. The composite scaffold released key growth factors for wound healing (FGF, TGFβ) and vascularization (VEGF, PDGF) for up to 14 days. In addition, the composite scaffold had enhanced mechanical properties (when compared to PRP gel alone), while providing a continuous upper surface of extracellular matrix (ECM) for keratinocyte seeding. The levels of the factors released from the composite scaffold were sufficient to sustain proliferation of key cells involved in wound healing, including human endothelial cells, mesenchymal stromal cells, fibroblasts, and keratinocytes; even in the absence of FBS supplementation. In functional in vitro and in vivo vascularization assays, our composite scaffold demonstrated increased angiogenic and vascularization potential, which is known to lead to enhanced wound healing. Upon pro-inflammatory induction, macrophages released lower levels of the pro-inflammatory marker MIP-1α when treated with PRPr; and released higher levels of the anti-inflammatory marker IL1-ra upon both pro- and anti-inflammatory induction when treated with the composite scaffold. Finally, our composite scaffold supported a co-culture system of human fibroblasts and keratinocytes that resulted in an epidermal-like layer, with keratinocytes constrained to the surface of the scaffold; by contrast, keratinocytes were observed infiltrating the PRP-free scaffold. This novel composite scaffold has the potential for rapid translation to the clinic by isolating PRP from a patient intraoperatively and combining it with regulatory approved scaffolds to enhance wound repair.

JNK-mediated Slit-Robo signaling facilitates epithelial wound repair by extruding dying cells

Multicellular organisms repair injured epithelium by evolutionarily conserved biological processes including activation of c-Jun N-terminal kinase (JNK) signaling. Here, we show in Drosophila imaginal epithelium that physical injury leads to the emergence of dying cells, which are extruded from the wounded tissue by JNK-induced Slit-Roundabout2 (Robo2) repulsive signaling. Reducing Slit-Robo2 signaling in the wounded tissue suppresses extrusion of dying cells and generates aberrant cells with highly upregulated growth factors Wingless (Wg) and Decapentaplegic (Dpp). The inappropriately elevated Wg and Dpp impairs wound repair, as halving one of these growth factor genes cancelled wound healing defects caused by Slit-Robo2 downregulation. Our data suggest that JNK-mediated Slit-Robo2 signaling contributes to epithelial wound repair by promoting extrusion of dying cells from the wounded tissue, which facilitates transient and appropriate induction of growth factors for proper wound healing.

Platelet-Rich Plasma with Endothelial Progenitor Cells Accelerates Diabetic Wound Healing in Rats by Upregulating the Notch1 Signaling Pathway

Diabetic wounds, as a kind of refractory wound, are very difficult to heal. Both endothelial progenitor cell (EPC) transplantation and platelet-rich plasma (PRP) can improve diabetic wound healing to some extent. However, PRP application cannot provide reparative cells, while EPC transplantation cannot replenish the required growth factors for wound healing. Thus, when applied alone, neither of these factors is sufficient for effective wound healing. Furthermore, the proliferation, differentiation, and fate of the transplanted EPCs are not well known. Therefore, in this study, we examined the efficacy of combined PRP application with EPC transplantation in diabetic wound healing. Our results indicated that PRP application improved EPC proliferation and migration. The Notch signaling pathway plays a key role in the regulation of the proliferation and differentiation of stem cells and angiogenesis in wound healing. The application of PRP upregulated the Notch pathway-related gene and protein expression in EPCs. Furthermore, experiments with shNotch1-transfected EPCs indicated that PRP enhanced the function of EPCs by upregulating the Notch1 signaling pathway. In vivo studies further indicated that the combination of PRP and EPC transplantation increased neovascularization, reduced wound size, and improved healing in rat wound models. Thus, PRP application can provide the necessary growth factors for wound healing, while EPC transplantation offers the required cells, indicating that the combination of both is a potent novel approach for treating diabetic wounds.

Dynamic covalent constructed self-healing hydrogel for sequential delivery of antibacterial agent and growth factor in wound healing

The conventional injectable hydrogels as wound dressing materials frequently encounter bacterial infection and lack self-healing ability. Besides, the hydrogels injected into the irregular wound sites are easily damaged by external forces, which further hinder wound healing. To make up for these deficiencies, we developed a novel hydrogel with the unique properties including dynamic covalent based self-healing, antibacterial and sequential drug release. This injectable and self-healing hydrogel was constructed via the dynamic reaction of aminated gelatin (NGel), adipic acid dihydrazide (ADH) and oxidized dextran (ODex). After injection or damage, the broken hydrogel pieces performed excellent self-healing capability to generate an integral hydrogel owing to dynamic imine and acylhydrazone bonds. Meanwhile, bFGF@PLGA microspheres and chlorhexidine acetate (CHA) were embedded into the hydrogels. This bFGF@PLGA/CHA/hydrogel presented a good biodegradability, and it could retain the morphological stability after swelling. Moreover, bFGF@PLGA/CHA/hydrogels achieved the sequential release of CHA and bFGF during the drug release assay. When topically applied onto the wound skin of rats, the hydrogels can effectively prevent infection at the early stages due to the rapid release of CHA, then further accelerate cell proliferation and wound healing through the sustained release of bFGF. These results indicate that the proposed self-healing hydrogel with sequential release properties is a highly promising dressing material for wound healing.

Current Insights into the Potential Misuse of Platelet-based Applications for Doping in Sports.

Platelet-based applications are currently used for the delivery of growth factors and other biomolecules as autologous biomaterials in regenerative medicine and cosmetic therapies. Many studies have revealed that platelet-based applications such as platelet-rich plasma and platelet releasate exhibit beneficial biological effects after a sports injury or trauma when administered locally by intramuscular injections. At present, treatment of the public, patients and athletes with platelet-based applications is permitted and regulated by the Food and Drug Administration and the World Anti-Doping Agency. Since 2011 the use of autologous platelet-rich plasma is permitted in competitive sports by the World Anti-Doping Agency, due to the lack of evidence in performance enhancement and anabolic effects. However, accumulating research has recently shed light on the role of platelet-derived growth factors in wound healing, skeletal myogenesis, muscle stem cell function and tissue regeneration. Although any ergogenic potential of platelet-rich plasma and platelet releasate on intact skeletal muscle and human sports performance remain to be established, novel evidence suggests that platelet-derived growth factors can modulate muscle, tendon, ligament, protein synthesis/degradation, vascularization, energy utilization and regenerative capacity in various experimental settings. Since platelet-based applications are currently not prohibited, they constitute a tool for potential abuse and doping in sports. The aim of this review is to critically discuss and assimilate current insights and biological evidence that set the ground for exploitation and misuse in competitive sports, and develop strategies to combat these activities.

Role of photobiomodulation on the activation of the Smad pathway via TGF-β in wound healing

Wound healing is an essential process in which the separated or destroyed tissue attempts to restore itself into its normal state. In some instances, healing is prolonged and remains stagnant in the inflammatory phase, and is referred to as a chronic wound. At a cellular and molecular level, many factors are required during the process of successful wound healing, such as cytokines, polypeptide growth factors and components of the extracellular matrix (ECM). Transforming growth factor-beta (TGF-β) is considered as one of the essential growth factors in wound healing. Working through the Smad pathway, it is the main inducer of fibroblast differentiation which is essential for wound healing. Photobiomodulation (PBM) shows significant advantages in wound healing, and may stimulate cellular processes and tissue regeneration that results in an increase in growth factors and a decrease in inflammatory cytokines. Moreover, it leads to enhanced cell proliferation, migration, angiogenesis, and increased adenosine triphosphate (ATP) and cytochrome C oxidase (CCO) activity. In this review paper, we discuss the effects of PBM and its role on the activation of the TGF-β/Smad pathway in the process of wound healing.

Effects of the Diabetes-Induced MicroRNA-155 on Wound Healing and Fibroblast Growth Factor 7 Expression

Impaired wound healing is a serious late-diabetic complication resulting in significant morbidity. MicroRNAs (miRNAs), post-transcriptional gene-regulators, are differentially expressed in several conditions, such as diabetes. To assess the mechanistic action of miRNAs in diabetic wound healing streptozotocin (STZ)-induced diabetic and control mice (n=6/group, 6 weeks of diabetes) were subjected to 6-mm full-thickness excisional wounds. Biopsies were obtained at days 3 and 10 post-wounding. Wound healing was delayed in diabetic mice (p<0.05). The skin miRNA profile was determined for up to 561 unique miRNAs using Taqman MicroRNA array cards. We identified 288 different robustly expressed miRNA in skin. While half of them were decreased more than 1.5 fold, 41 were increased more than 1.5 fold, during wound healing. MiR-155-5p was increased in diabetic skin (15.8 fold (95% CI: 3.5-28.1), however, it was 9.7 fold (95% CI: 4.2-15.2) decreased at day 10 post wounding, as compared to nondiabetic mouse skin. Scratch assays in HaCaT cells showed increased scratch closure after 24 hours, when miR-155 was inhibited (Ctrl: 31%, miR-155 inhibitor: 8.1% of scratch remaining, P<0.001). In vivo, topical treatment of diabetic mouse wounds with miR-155 inhibitor dose-dependently accelerated wound closure with maximal effect at 2.5pmol (P<0.03). Interestingly, reporter-gene analysis identified fibroblast growth factor (FGF) 7 mRNA as a target of miR-155-5p. Moreover, miR-155 inhibitor treated mouse wounds showed significant increase in FGF7 protein expression by immunofluorescence. We present evidence that miR-155-5p expression is altered in diabetic mouse skin and its suppression significantly improves wound healing under diabetic conditions, indicating its potential as a novel chronic diabetic foot ulcer treatment. Disclosure L.T. Dalgaard: Employee; Spouse/Partner; Novo Nordisk A/S. Stock/Shareholder; Spouse/Partner; Novo Nordisk A/S. Stock/Shareholder; Self; Novo Nordisk A/S. E.C. Leal: None. R. Svendsen: None. J. Moura: None. A.E. Sørensen: Research Support; Self; Danish Diabetes Academy, Merck Serono. P.T. Jørgensen: None.

Combined Topical Growth Factor and Protease Inhibitor in Chronic Wound Healing: Protocol for a Randomized Controlled Proof-of-Concept Study.

BackgroundLeg ulcers due to venous disease are chronic wounds that can take 6 or more months to heal. Growth factors have been used to try and improve this healing; however, many such studies have failed, and that is thought to be due to enzymes in the wound that degrade the growth factors and prevent them from working.ObjectiveThis is a proof-of-concept study that will evaluate the treatment of chronic leg ulcers with topically applied growth factors that are combined with a therapy to prevent their inactivation in the wound. This combined therapy has the potential to speed up the healing of these wounds and thereby improve the quality of life of patients and reduce the costs to the health system.MethodsThis will be a double-blind, placebo-controlled, randomized controlled proof-of-concept study comparing growth factor with protease inhibitor wound dressings to growth factors with standard wound dressings.ResultsThe project was funded by the Canadian Institutes for Health Research and enrollment is expected to be initiated in 2018. It is expected that results will be available in 2021.ConclusionsIt is expected that the results of this trial will inform as to whether modifying the wound environment through the use of protease inhibitors increases the effectiveness of topically applied growth factors in the healing of chronic wounds.Trial RegistrationClinicalTrials.gov NCT02845466; https://clinicaltrials.gov/ct2/show/NCT02845466 (Archived by WebCite at http://www.webcitation.org/6yOPhSBUA)

Studies on the use of recombinant spider silk protein/polyvinyl alcohol electrospinning membrane as wound dressing.

A series of wound membranes of polyvinyl alcohol and recombinant spider silk protein (pNSR16) was prepared by electrospinning. The membrane was analyzed by scanning electron microscopy, atomic force microscopy, and Fourier transform infrared spectroscopy. The result showed that the three factors that affected average fiber diameter from high to low were, voltage, flow speed, and solidification distance; and the three factors that affected fiber uniformity from high to low were, flow speed, solidification distance, and voltage. The fibers adhered together after being dealt with alcohol. pNSR16 transformed from random coil into β-sheet after being immersed in alcohol. Additionally, the porosity of the electrospun membrane was 84.85%, which was higher than that of cast membrane prepared with the same composition. Experiments of applying electrospun membranes as wound dressing for Sprague Dawley rat wound healing showed that it could promote wound healing and basic fibroblast growth factor expression.

Advanced Growth Factor Delivery Systems in Wound Management and Skin Regeneration.

Growth factors are endogenous signaling molecules that regulate cellular responses required for wound healing processes such as migration, proliferation, and differentiation. However, exogenous application of growth factors has limited effectiveness in clinical settings due to their low in vivo stability, restricted absorption through skin around wound lesions, elimination by exudation prior to reaching the wound area, and other unwanted side effects. Sophisticated systems to control the spatio-temporal delivery of growth factors are required for the effective and safe use of growth factors as regenerative treatments in clinical practice, such as biomaterial-based drug delivery systems (DDSs). The current review describes the roles of growth factors in wound healing, their clinical applications for the treatment of chronic wounds, and advances in growth factor-loaded DDSs for enhanced wound healing, focusing on micro- and nano-particulate systems, scaffolds, hydrogels, and other miscellaneous systems.

Liposomes with Silk Fibroin Hydrogel Core to Stabilize bFGF and Promote the Wound Healing of Mice with Deep Second-Degree Scald.

How to maintain the stability of basic fibroblast growth factor (bFGF) in wounds with massive wound fluids is important to accelerate wound healing. Here, a novel liposome with hydrogel core of silk fibroin (SF-LIP) is successfully developed by the common liposomal template, followed by gelation of liquid SF inside vesicle under sonication. SF-LIP is capable of encapsulating bFGF (SF-bFGF-LIP) with high efficiency, having a diameter of 99.8 ± 0.5 nm and zeta potential of -9.41 ± 0.10 mV. SF-LIP effectively improves the stability of bFGF in wound fluids. After 8 h of incubation with wound fluids at 37 °C, more than 50% of free bFGF are degraded, while only 18.6% of the encapsulated bFGF in SF-LIP are destroyed. Even after 3 d of preincubation with wound fluids, the cell proliferation activity and wound healing ability of SF-bFGF-LIP are still preserved but these are severely compromised for the conventional bFGF-liposome (bFGF-LIP). In vivo experiments reveal that SF-bFGF-LIP accelerates the wound closure of mice with deep second-degree scald. Moreover, due to the protective effect and enhanced penetration ability, SF-bFGF-LIP is very helpful to induce regeneration of vascular vessel in comparison with free bFGF or bFGF-LIP. The liposome with SF hydrogel core may be a potential carrier as growth factors for wound healing.

Growth factors in wound healing: Upregulation of VEGF and TGF expressions by a topical amide

Growth factors in wound healing: Upregulation of VEGF and TGF expressions by a topical amide

Biologically Triggered Delivery of EGF from Polymer Fiber Patches.

Wound healing is modulated by complex spatial and temporal regulation of growth factors within a wound site. Regenerative medicine seeks to generate materials that can mimic this environment for the healing of chronic or traumatic wounds. Herein, we report a programmed release of epidermal growth factor (EGF) from coextruded polymer fiber patches, which is triggered by the natural biological cascade of wound healing. Genetically engineered EGF containing a matrix metalloproteinase (MMP) cleavage site was covalently conjugated to a nonwoven poly(ε-caprolactone) (PCL) fiber mat fabricated by multilayered melt coextrusion. The genetically modified EGF showed rapid release in the presence of a biological trigger, MMP-9, while a control protein showed negligible release. The biologically responsive fiber mat dramatically enhanced proliferation and migration of human keratinocytes in the presence of MMP-9. This study describes the release of a critical wound-healing growth factor as triggered by the biology inherent in the healing process.

Adipose-derived stem cells seeded in Pluronic F-127 hydrogel promotes diabetic wound healing

BackgroundChronic nonhealing wound is a multifactorial complication of diabetes that results specifically as a consequence of impaired angiogenesis and currently lacks in effective treatments. Although a stem cell–based therapy may provide a novel treatment to augment diabetic wound healing, inferior cell survival at the diabetic skin wound is one of the key causes that are responsible for the low efficacy of the stem cell therapy. Materials and methodsIn this work, we used an injectable, biocompatible, and thermosensitive hydrogel Pluronic F-127 to encapsulate allogeneic nondiabetic adipose-derived stem cells (ADSCs) and topically applied the cells to a full-thickness cutaneous wound in the streptozotocin-induced diabetic model in rats. ResultsThe cells seeded in the hydrogel enhanced angiogenesis (CD31 marker) and promoted the cell proliferation (Ki67 marker) at the wound site and significantly accelerated wound closure, which was accompanied by facilitated regeneration of granulation tissue. Consistently, levels of the messenger RNA expression of key angiogenesis growth factor, vascular endothelial growth factor, and key wound healing growth factor, transforming growth factor beta 1, were also upregulated in the cell-treated wounds when compared with untreated wounds. ConclusionsThe results indicated that the transplantation of allogeneic ADSCs via the hydrogel improves the efficiency of cell delivery and optimizes the performance of ADSCs for augmenting diabetic wound healing. In conclusion, this ADSC-based therapy may provide a novel therapeutic strategy for the treatment of nonhealing diabetic foot ulcers.

Feasibility of improving platelet-rich plasma therapy by using chitosan with high platelet activation ability.

Platelet-rich plasma (PRP) is blood plasma containing a high number of platelets that release growth factors for wound healing and tissue regeneration. In the present study, the feasibility of improving PRP therapy by using chitosan that exhibits high platelet activation ability was investigated. A total of 13 chitosan samples with different molecular weight (Mw) and degree of deacetylation (DDA) were individually added to blood samples of rats and the amount of growth factors, albumin and fibrinogen in plasma was measured. To examine the influence of plasma activated by chitosan on the proliferation of fibroblasts and adipose tissue-derived stromal cells (ASCs), the plasma was added to the culture medium of human fibroblasts and adipose tissue-derived stromal cells. Chitosan with a DDA of >75% increased the release of platelet factor 4 into the plasma. The amount of growth factors released into the plasma and platelet activation varied depending on the Mw and DDA, while albumin and fibrinogen were hardly affected. The proliferation rate was highest when using plasma activated by chitosan with a DDA of 75-85% and an Mw of 50,000-190,000 Da. These results suggested that the effectiveness of PRP therapy may be improved by using chitosan with a DDA of 75-85% and an Mw of 50,000-190,000 Da.

Models for the study of skin wound healing. The role of Nrf2 and NF-κB.

Nrf2 and NF-κB transcription factors act in wound healing via their anti-inflammatory and anti-oxidant effects or through the immune response. Studying this process is a matter of some importance given the high cost of wound treatment. A major contribution in this regard is being made by models that enable investigation of the involvement of multiple factors in wound healing and testing new curative substances. This literature review was carried out via searches in the PubMed and Web of Science databases up to 2016. It covers skin wound healing, available models for its study (part I), the role of Nrf2 and NF-κB, substances that influence them and whether they can be used as markers (part II). Was found that in vitro assays are used for their availability but a holistic view must be established in vivo. In silico approaches are facilitating assessment of a vast amount of research data. Nfr2 and NF-κB play a crucial and reciprocal role in wound healing. Nrf2 controls repair-associated inflammation and protects against excessive accumulation of ROS while Nf-κB activates the innate immune reaction, proliferation and migration of cells, modulates expression of matrix metalloproteinases, secretion and stability of cytokines and growth factors for wound healing.

Prospective study of platelet derived growth factor in wound healing of diabetic foot ulcers in Indian population

Background: Recently the world health organization reported a global prevalence of diabetes exceeding 300 million people, predicting a further 60-70% increase by the year 2030, which means India alone will have 100 million people by the year 2030.Wound healing is problematic in diabetic patients. Encouraging results have shown that PDGF application is better than good wound care alone. But the evidence to demonstrate the safety and efficacy of PDGF in diabetic ulcer is scanty.Methods: The present study was carried out at PSG Hospitals, Coimbatore, Tamil Nadu, India for a period of one year, where 50 patients with diabetic foot ulcers were included in the present study. Prospective randomized controlled trail was designed for the study. 50 patients with diabetic foot ulcers admitted in surgery wards at PSG Hospitals over a period from August 2011 to August 2012. 25 patients were in the study/treatment group, 25 patients were in the control group.Results: Out of 50, patients, 25 took treatment in the form of conventional normal saline dressings and 25 took treatment with rh - PDGF dressing once a day. Glycaemic control and adequate control of infection was maintained in both the groups. X-ray foot was taken for all patients and bony involvement was excluded. The initial area measurement was taken on day 01 and final area measurement on day 15 was taken on transparent sheet. Plannimetry was used to measure the outcome that is the target ulcer area using a transparent graph sheet. Results were calculated by using student ‘t’ test.Conclusions: The wounds in the study group treated with rh-PDGF dressing contracted more than the wounds in the control group (38.55% Vs 12.79%; P≤ 0.001- statistically significant) which indicates rh-PDGF dressing is an effective modality to facilitate wound contraction in patients suffering from diabetes. Rh-PDGF dressing is found to be more effective, safe promoter of wound healing and can be used as an adjunct to saline dressing for healing of diabetic wounds and healing of ulcers receiving PDGF was significantly faster as compared to ulcers receiving placebo.