An injectable GelMA hydrogel improves Achilles tendon repair through local microenvironment modulation

Achilles tendon injury remains a major clinical challenge because of its limited intrinsic healing capacity and the high risk of disorganized extracellular matrix remodeling during repair. In this study, we developed an injectable gelatin methacryloyl (GelMA) hydrogel loaded with GsMTx4, a mechanosensitive ion channel modulator, for sustained local delivery and evaluated its therapeutic potential for Achilles tendon healing in vitro and in vivo. The hydrogel exhibited favorable physicochemical properties, injectability, and local retention capacity. Biological evaluation showed that treatment with this delivery system was associated with improved cell compatibility, reduced matrix degradation, and enhanced expression of tendon-related markers. In the Achilles tendon injury model, local administration promoted histological repair, improved collagen organization, and alleviated pathological changes in the injured tissue. These beneficial effects were accompanied by modulation of extracellular matrix remodeling and mechanosensitive responses. Collectively, these findings suggest that this injectable GelMA hydrogel-based delivery strategy may serve as a promising local therapeutic approach for improving Achilles tendon repair.