Micropeptide-Inspired Engineered Stapled Peptide-Loaded Hydrogel Platform Promotes Skeletal Muscle Repair After...

Skeletal muscle is a highly organized tissue possessing an intrinsic regenerative capacity; however, severe injury often results in incomplete functional recovery due to persistent inflammation and fibrotic tissue deposition. Current therapeutic strategies rely on anti-inflammatory drugs, stem cell therapies, and growth factors but have shown limited clinical success. Herein, we developed a micropeptide-inspired stapled peptide, M.R., which exhibits potent regenerative capacity at nanomolar concentrations with enhanced stability and efficacy by promoting myogenic differentiation, modulating inflammation, and limiting fibrosis. Further, M.R was encapsulated within a borax-functionalized guar gum hydrogel, providing a biocompatible platform for sustained release of therapeutic lead and promoting muscle repair following a cryolesion-induced muscle injury model. Overall, this study introduces a first-in-class peptide-based therapeutic lead, M.R., encapsulated within a biocompatible hydrogel platform for promoting muscle repair through a multidimensional regenerative approach.