Diabetic foot, venous stasis and pressure ulcers are examples of chronic non healing wounds that are refractory to standard therapy and represent a major health care problem especially for the increasing elderly population. Polypeptide growth factors are a class of biological mediators which have been proposed as possible vulnerary agents. The combination of platelet-derived growth factor (PDGF) and epidermal growth factor (EGF) has been shown to be more potent that individual growth factors in stimulating the healing of partial thickness skin wounds in healthy swine. In preparation for testing this composition on diabetic mice of PDGF-BB, EGF or the combination project will examine the dose dependent efficacy on wounds in diabetic mice PDGF-BB, EGC or the combination of PDGF-BB/EGF delivered in a 2% methylcellulose gel vehicle. Specifically, investigators will evaluate the healing of full thickness wounds on genetically diabetic mice (C57BL/KsJ-db/db) following the repeated application of: 1) 4.0 mug PDGF-BB, 15mug PDGF-BB and 50mug EGF per cm wound surface are, 2) 4.0mug PDGF-BB, 3)4.0mug PDGF-BB 60mug EGF or 4.0 PDGF-BB and 60mug EGF per cm wound surface area. Control wounds will receive vehicle alone. Gel treatments will be applied immediately following surgery and 2, 4, and 6 days, thereafter. At the time of surgery and at days 8, 10, 12, 14 and as needed thereafter, standardized photographs will be taken of each wound for wound closure analysis. Complete wound biopsies will be harvested on day 14 for histologic and hydroxyproline analyses. Statistical analyses will be performed for wound closure, histological and hydroxyproline data using Analysis of Variance (ANOVA), Kruskal-Wallis test and Student's t-test, respectively. The results from these studies will elucidate appropriate dose levels for initial evaluation in human clinical trials in chronic wounds of diabetic patients.
