A 3-Dimensional Bioprinted Decellularized Umbilical Cord Matrix Patch for Enhanced Storage and Delivery of Extracellular Vesicles in Diabetic Wound Healing

Extracellular vesicles (EVs) are promising cell-free therapeutics for diabetic wound healing due to their immunomodulatory and proangiogenic properties. Nonetheless, challenges in ensuring long-term stability and achieving targeted delivery continue to impede clinical translation. Herein, we developed a 3-dimensional bioprinted methacrylated decellularized umbilical cord matrix (MDUM) patch enabling the sustained delivery of telomerase-immortalized umbilical cord mesenchymal stem cell-derived EVs (TMSC-EVs). TMSC-EVs encapsulated in MDUM maintained their structural integrity and biological functionality for more than 30 d under 4 °C storage, outperforming those encapsulated in gelatin methacryloyl ( P < 0.01). In a diabetic murine wound model, our data demonstrated that MDUM could enhance the retention and delivery of TMSC-EVs and further augment the therapeutic effects for diabetic wound healing as revealed by attenuating proinflammatory cytokine levels, enhancing neovascularization, and accelerating collagen deposition. This study pioneers the integration of biomaterial engineering with immortalized cell-derived EVs, establishing a translatable platform for regenerative therapies in chronic wound management.