Treatment of Denervated Muscle Atrophy by Injectable Dual-responsive Hydrogels Loaded with Extracellular Vesicles

Denervated muscle atrophy often causes irreversible fibrosis due to inefficient treatments. A novel ultrasound and pH-responsive hydrogel was created to deliver stem cell-derived EVs, enhancing treatment outcomes. Made from crosslinked carboxymethyl chitosan, oxidized chondrotin sulfate, and cystamine, it degrades under ultrasound and acidic conditions for controlled EV release. The hydrogel, when loaded with human umbilical cord-derived EVs, significantly preserved muscle function and restored strength, circumference, and weight post-nerve reconstruction, offering a promising therapy for atrophy.