Non-healing wounds caused by diabetes mellitus account for one of the most common complications of this disease leading to increased healthcare expenditures, decreased quality of life, infections, amputations, and death. The fabrication of a material biochemically modified to promote angiogenesis, and with tunable material properties would present a promising solution to the problems currently encountered in diabetic wound healing.
The aim of this work is to engineer a bioactive scaffold designed to overcome the impairments present in diabetic wound healing. These include angiogenic growth factor deficiency, endothelial progenitor cell (EPC) homing to the wound site, and vascularization at the wound bed. The cytokines stromal cell-derived factor-1a (SDF-1a) and WNT5A have a crucial role in EPC homing and angiogenesis, respectively, and both have been implicated in diabetic wound healing. Here, we propose the fabrication of a WNT5A/SDF-1a-activated biomaterial as a dermal scaffold to improve healing of diabetic ulcers. We envision that the bioactive scaffold will recruit EPCs to the wound site via the controlled release of SDF-1a from polymeric microparticles, and promote the ingrowth of blood vessels from the local environment via the presentation of WNT5A. Finally, we believe increased vascularization at the wound bed will hasten wound healing and enable complete skin regeneration. It is envisioned that this work will not only lay the foundation for future clinical trials, but also be beneficial o other types of wounds such as arterial and venous insufficiency wounds, pressure ulcers, and burns.
Diabetic ulcers stemming from impaired wound healing are a common complication of patients with diabetic mellitus and a leading cause of non-traumatic amputations in the United States. Given the high economic and healthcare burden of treating these wounds, and the projected increase in the prevalence of diabetes from the current population of 25.8 million Americans with diabetes, a solution is urgently needed. We propose to create a tissue engineered dermal scaffold to uniquely present and deliver angiogenic factors for promoting the healing of diabetic wounds. The proposed work outlined presents a promising and trans-disciplinary approach towards finding a solution to this significant and unmet clinical need.
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