Multifunctional Hydrogel Integrated Hemangioma Stem Cell‐Derived Nanovesicle‐Loaded Metal‐Polyphenol Network Promotes Diabetic Flap Survival

A novel vascularization treatment system consisting of a hybrid photo-crosslinked hydrogel (HPC) encapsulating a dual-metal-polyphenol network (dMPN) loaded with hemangioma stem cell-derived nanovesicles (HemVs) (HemV@dMPN/HPC) is developed. This system can promote diabetic flap graft survival by promoting vascularization, regulating inflammation, and inhibiting bacterial growth.

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 (Cu²⁺) and magnesium ions (Mg²⁺), stimulating angiogenesis and mitigating inflammation. The HPC further sustains ion release while preserving the therapeutic efficacy of HemVs. Moreover, both HPC and Cu²⁺ 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.