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 transforming growth factor-beta1 (TGF-beta1,) and insulin-like growth factor-I (IGF-I) has been shown to significantly enhance the healing of partial thickness skin wounds in healthy swine. In preparation for testing this composition on chronic ulcers in human clinical studies, this project will examine the dose dependent efficacy on wounds in diabetic mice of TGF-beta1, IGF-I or the combination of TGF-beta1/IGF-I delivered in a 2% methylcellulose gel vehicle. Specifically, investigators will evaluate the healing of full thickness wounds on genetically diabetic mice (C57BL/KsJdb/db) following the repeated application of: 1) 1.0 mu g of either TGF-beta1, IGF-I or the TGF-beta1/IGF-I combination 2) 5.0mu g of either TGF-beta1, IGF-I or the TGF-beta1/IGF-I combination. Control wounds will receive either the vehicle or dressing only. 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 and 14, 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. In phase II studies investigators will continue to optimize the efficacy of the most promising composition. The results from these studies will elucidate appropriate dose levels for initial evaluation in human clinical trials in patients with chronic wounds of diabetic patients.