Progression of diabetic foot ulcers is the leading cause of lower limb amputation in the U.S. The high incidence of diabetic foot complications demonstrates aggressive conventional therapy is neither realistically accomplished, nor cost-effective. Furthermore, conventional therapy does not treat the causative microcirculatory pathology. The overall project goal is to evaluate Encelle, Inc.'s proprietary hydrogel matrix (E-Matrix) as a single injection therapy for vascularization of skin lesions. The project will develop characterization assays for E-Matrix to understand the physical and chemical properties of the matrix, measure manufacturing consistency and E-Matrix stability. Efficacy will be evaluated using two wound models resulting from compromised vasculature in pigs. Surgical interruption of the skin vasculature, or phenol chemical burns, will be induced at six separate sites in two cohorts of four pigs each. The effect on wound size and rate of closure following no treatment, a single control injection, or a single E-Matrix injection circumferentially and centrally, will be studied. After 14 days, the animals will be sacrificed, and tissue samples obtained for immunohistochemical preparation and analysis. Tissue analysis using histological and immunohistochemical methods will qualitatively and semi-quantitatively delineate the vascular density at wound sites, differentiation of blood vessel types, the number and type of infiltrating cells, mitotic indices, apoptosis during healing, amount and type of collagen formed and induction of metalloproteinases. Understanding the detailed tissue and cellular response to E-Matrix treatment using reproducibly manufactured E-Matrix with known physical and chemical characteristics in well-defined animal models will provide a strong baseline for the commercial development of this product.
Potential applications of E-Matrix include the treatment of conditions associated with compromised vascular flow including diabetic ulcers, decubitus ulcers, burns, atherosclerosis of the peripheral vasculature, coronary artery disease, and stroke.
