Ultrasound-Activated GelMA Hydrogel Loaded with MSC-EVs Promotes Functional Regeneration of Skin Vasculature, Nerves, and Appendages

The study presents a novel bioengineered approach to enhance skin regeneration using a combination of ultrasound stimulation and a GelMA hydrogel loaded with mesenchymal stem cell-derived extracellular vesicles (MSC-EVs). This method addresses the challenge of poor delivery efficiency of MSC-EVs by using ultrasound to enhance their internalization through calcium-dependent cytoskeletal remodeling. The approach significantly improved fibroblast viability, migration, and secretory functions in vitro and accelerated wound healing in a murine model, achieving 90% closure by Day 14. It also promoted neovascularization, neurogenesis, and hair follicle regeneration. The findings suggest that this synergistic integration of physical and biochemical cues could transform regenerative therapeutics for skin injuries.