Chronic wounds present a significant clinical challenge due to impaired skin microvasculature, particularly in diabetes. The tissue engineering study introduces therapeutic Exo-Q, a unique thermoresponsive polymer hydrogel created with Q protein nanofibers and cultured human bone marrow multipotent stromal cell exosomes with consistent gene signature. Limited, local and topical application of Exo-Q hydrogel is feasible for maximum neovascularization during murine diabetic wound closure in a xenotransplantation model, as well as compatibility and vascular delivery in human skin in a xenograft model. Exo-Q hydrogel treatment significantly reduces diabetic wound closure time within ranges of non-diabetic wounds. This innovative, non-invasive tissue engineered therapeutic option offers a promising approach to addressing the complex pathologies of non-healing wounds.