Development of treatments to improve healing of ischemic wounds

Between 15-25% of the ~29 million diabetic Americans develop serious foot ulcers; ~65% of these ulcers have ischemic pathology and frequently become chronic wounds due to impaired healing. To improve healing of chronic ischemic ulcers, researchers have sought to increase angiogenesis at the wound site using angiogenic growth factors. However, the clinical success of growth factor therapies for chronic wounds has been limited largely due to the overexpression of matrix metalloproteases (MMPs) that degrade or inactivate the growth factors in the wound environment. The excess MMPs also promote degradation of the newly formed granulation tissue and counteract healing. To overcome the limitations of loss of VEGF and granulation tissue due digestion by MMPs, and systemic diffusion of VEGF, we have developed a glycosaminogycan based molecule that binds to and protect the matrix from degradation and also stimulates VEGF receptor 1 to promote angiogenesis and healing.

This therapeutic, called SILY-DS-LXW7 binds to and protects collagen based tissue and stimulates VEGF receptors on EPCs. We co-administered the SILY-DS-LXW7, EPCs, and a collagen scaffold to provide a provisional, pro-angiogenic scaffold to support tissue regeneration while limiting systemic exposure to VEGF activity. Our data demonstrated improved time in wound closure in diabetic ischemic wounds and supports further development of the therapeutic.