DescriptionDiabetic 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 (sRAGE) and improve SDF-1 persistence using a liposome delivery system. To test the effectiveness of SDF-1, a transwell migration assay was developed, where Human Leukemia-60 (HL-60) cells, that contain the CXCR4 receptor, migrate through a porous membrane towards a supply of SDF-1. The major finding using this assay was that, as SDF-1 increases, percent cell migration increases. In addition, when HL-60 cells are pre-treated with 25mM extra glucose in cell media for 24 hours, cell migration decreased compared to cells cultured with plain media and media supplemented with L-glucose. sRAGE treatment reversed this impairment and restored migration. The mechanism causing this phenomenon is the increased superoxide ion (O2-) in increased glucose cultures, which was measured through dihydroethidium. The SDF-1 liposomes were created using standard self assembly methods and also induced HL-60 cell migration in the transwell. SDF-1 liposomes maintained the induction of a calcium response associated with SDF-1 signaling. The SDF-1 liposomes also rapidly and uniformly infiltrated dermal scaffolds Alloderm® and Integra®. In an in vivo diabetic excisional wound model, sRAGE alone was not enough to restore SDF-1 function. However, SDF-1 liposomes sped up wound closure by 1 week over the controls through increased dermal cell proliferation and promotion of wound contraction.