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

The study presents a novel approach to enhance skin regeneration using a combination of ultrasound stimulation and a GelMA hydrogel delivery system 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, which in turn amplifies regenerative pathways such as angiogenesis, matrix modulation, and neural repair. In vitro experiments showed that ultrasound synergized with MSC-EVs significantly improved fibroblast functions. In a mouse model with full-thickness wounds, this system accelerated wound closure, promoted neovascularization and neurogenesis, and facilitated hair follicle regeneration. The study identifies ultrasound-driven calcium influx and actin depolymerization as key mechanisms for enhanced MSC-EVs uptake, offering a promising strategy for functional skin regeneration.