Multifunctional Hydrogel Integrated Hemangioma Stem Cell‐Derived Nanovesicle‐Loaded Metal‐Polyphenol Network Promotes Diabetic Flap Survival
Rui Chang, Pei Wang, Hongrui Chen, Shih‐Jen Chang, Qianyi Chen, Lei Chang, Yajing Qiu, Xiansong Wang, Xiaoxi Lin
Abstract
Abstract Diabetes‐associated skin defects represent a significant global health challenge. While flap grafts have been a preferred treatment for soft‐tissue injuries in diabetic patients, their survival is often compromised by impaired vascularization, infection, and the adverse diabetic pathological microenvironment. To address these limitations, a hybrid photo‐crosslinkable hydrogel (HPC) integrated hemangioma stem cell‐derived nanovesicle (HemV)‐loaded dual‐metal‐polyphenol network (dMPN) (HemV@dMPN/HPC) is developed. HemVs, derived from highly vascularized infantile hemangioma tissues, play a key role in promoting cell proliferation and angiogenesis. The dMPN facilitates the gradual release of copper (Cu 2+ ) and magnesium ions (Mg 2+ ), stimulating angiogenesis and mitigating inflammation. The HPC further sustains ion release while preserving the therapeutic efficacy of HemVs. Moreover, both HPC and Cu 2+ act to confer antibacterial properties, further accelerating wound healing. This multifunctional HemV@dMPN/HPC platform offers a promising therapeutic strategy for treating large diabetic skin defects and can potentially improve flap graft survival.