Synergistic effects of conductive hydrogels and electrical stimulation in volumetric muscle loss

Abstract

Functional biomaterials capable of providing regenerative environments have been widely studied to facilitate efficient repair of volumetric muscle loss (VML). In this study, we devised an injectable conductive hydrogel composed of MXene (Ti3C2Tx), a conductive nanoparticle, and hexanoyl glycol chitosan (HGC), a thermoresponsive polymer, for VML muscle regeneration. Especially, the MXene-containing HGC hydrogel (HGC-MX) with 3 mg/mL MXene and 3 % HGC exhibited good injectability with the sol–gel transition at physiologically relevant temperature (approximately 30 °C) and conductivity (0.8 mS/cm), which can effectively create electroactive environments. Animal studies using a mouse VML defect model revealed that HGC-MX injection significantly facilitated muscle regeneration, as evidenced by enhanced muscle strength recovery, increased skeletal muscle fiber maturation, and reduced fibrosis. Electrical stimulation with HGC-MX further enhanced muscle fiber maturation and angiogenesis, demonstrating its synergistic effect with the conductive hydrogel for muscle regeneration. Overall, our injectable conductive hydrogels provide favorable environments and permit efficient electrical stimulation for skeletal muscle regeneration after VML injury. Our HGC-MX hydrogels can serve as promising and effective platforms for the regeneration of various electroactive tissues, including muscles and nerves. © 2025 Elsevier B.V.