ABSTRACT Chronic nonhealing wounds are debilitating with high morbidity and mortality. It is widespread and costly to treat (e.g. ~ $15 billion/year for venous leg ulcers in the United States alone). Despite extensive efforts to develop therapeutic strategies for effective treatment of chronic wounds, so far, limited clinical success has been achieved. Currently available devices and products are designed only to target one or more complex impaired cellular and molecular functions in chronic wounds. The increasing clinical significance and medical and social responsibilities to treat and cure chronic skin wounds are driving the demand for development of efficiently designed and fabricated wound-healing devices. A system that not only possesses the physico-mechanical properties of skin, but also corrects or avoids the impaired molecular and cellular machinery of chronic wounds, including angiogenesis, epithelial migration and cell proliferation, unresolved inflammation, and infection, would be a major advance. The proposed research project is aimed to develop a multifunctional patch with a unique capacity to resume bodies' capacity to heal chronic wounds. In this regards, we develop a nanoextrusion approach to fabricate a multifunctional nanofibrous composite patch capable of addressing the main challenges associated with the healing process of chronic wounds, including i) providing a suitable environment in which cells can easily proliferate and form new blood vessels; ii) preventing or reducing existing bacterial infection using ferumoxytol nanoparticles with and without protein corona; and iii) minimizing unbalanced and prolonged inflammation. We plan to homogeneously incorporate multi-functional biomolecules (e.g., follistatin-like 1, Ac2-26, and ferumoxytol nanoparticles) within its fibrous framework to accelerate angiogenesis and cell proliferation, while minimizing the risk of bacterial infection and prolonged inflammation. A wide range of in-vitro and in-vivo therapeutic efficacy of the novel patches will be conducted. For the in-vivo experiments, we use a rat models of diabetes provided by Charles River to probe the therapeutic and antibacterial efficacy of the patch. Involved mechanisms of the cell and immune system interactions with the multifunctional patch will be identified using a wide range of analysis including advanced electron microscopy. This study will pave the way for the development of new tissue engineering scaffolds to improve the body's natural (endogenous) repair mechanisms by redirecting impaired healing pathways, thus providing a unique opportunity to repair and regenerate damaged skin and tissue in a wide range of chronic wounds.