Research Project
7613269
Abstract Chronic non-healing wounds represent a significant complication of diabetes, resulting in significant morbidity, lost productivity, and healthcare expenditures. The rising incidence of obesity and diabetes has increased the number of people at risk for diabetic wounds. Despite the enormous impact these chronic wounds have, effective therapies have been lacking. The correction or prevention of diabetes impaired wound healing has far reaching consequences on patient outcomes, healthcare expenditures, and public health. Normal wound healing is an intricate process involving multiple growth factors, cell types, and complex signaling interactions. Alterations in growth factor and chemokine production, cellular recruitment, angiogenesis, extracellular matrix production, and wound contraction have all been shown to contribute to the diabetic wound healing impairment. While these factors have been implicated as potential etiologies in the diabetic wound healing impairment, very little information is available about the biomechanical properties of the diabetic dermis prior to injury or following wound closure. Tissues with inferior biomechanical properties are structurally and/or materially weakened and are at high risk for injury, degeneration, failure or other pathologies. We have recently demonstrated that the diabetic dermis has inherently inferior biomechanical properties at baseline, prior to injury, which puts the tissue at increased risk for damage and/or failure when compared to non-diabetic skin. We have recently demonstrated that treatment of diabetic wounds with stromal progenitor cells (SPC) or lenti-viral overexpression of SDF-1[unreadable], a chemokine involved in progenitor recruitment, can correct the impairment in diabetic wound closure. We hypothesize that SPC, or strategies to increase progenitor recruitment, can correct the inferior biomechanical properties of the diabetic dermis and improve the subsequent wound healing following injury. In addition, characterization of the mechanisms involved in SPC or lenti-SDF-1[unreadable] mediated correction of the diabetic wound healing impairment will provide further insight into strategies to modify the diabetic wound healing response.
