Strategies for improving growth factor function in diabetic wounds

TL;DRAbstract

Diabetic Foot Ulcers (DFUs) are debilitating non-healing wounds that often lead to amputation. The dermal scaffold is a promising treatment strategy that provides a template for cell migration and vascularization. Nevertheless, they fail in many instances due to the pro-inflammatory state of the wound, which includes increased matrix metalloproteases (MMPs) that degrade growth factors. MMPs act on both endogenous and exogenous growth factors that are added to the wound to aid in healing. Therefore, the goal of this project is to improve growth factor treatments delivered in dermal scaffolds by specifically packaging them to survive the diabetic milieu. The growth factor used here, stromal cell-derived factor-1 (SDF-1) is a chemokine that binds to the CXCR4 receptor on stem and progenitor cells; it is down-regulated in diabetes. This dissertation aims to improve SDF-1 action by blocking the pro-inflammatory receptor for advanced glycation end products (RAGE) pathway with soluble RAGE (s

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