GelMA Hydrogel Loaded with Extracellular Vesicles Derived from Umbilical Cord Mesenchymal Stem Cells for Promoting Cutaneous Diabetic Wound Healing.

Chronic diabetic wounds have become a significant cause of disability worldwide. It is highly desired to develop effective therapies that can promote the rapid healing of diabetic wounds. Owing to the outstanding hydrophilic and water-retaining properties, hydrogels could accelerate the healing process. Extracellular vesicles (EVs) have shown the ability to promote cell regeneration and angiogenesis. In this study, we chose a gelatin methacryloyl (GelMA) hydrogel, a kind of biomaterial characteristic of good biocompatibility, to load the EVs derived from umbilical cord mesenchymal stem cells (UCMSCs) in order to have a long-lasting effect by consistent release of EVs. Then, the hydrogel with EVs was used to treat diabetic wounds in rat models. Nuclear magnetic resonance spectroscopy and scanning electron microscopy were used to characterize the synthesis of the hydrogel; cell experiments, animal experiments, and histological staining were used to evaluate the function of the hydrogel with EVs. The results show that the GelMA hydrogel incorporated with the UCMSC-derived EVs exhibits unique physicochemical properties, excellent biocompatibility, and much enhanced therapeutic effects for diabetic wounds.