Bioactive Nb 2 C MXene‐Functionalized Hydrogel with Microenvironment Remodeling and Enhanced Neurogenesis to Promote Skeletal Muscle Regeneration and Functional Restoration

The complete structure-functional repair of volumetric muscle loss (VML) remains a giant challenge and biomedical hydrogels to remodel microenvironment and enhance neurogenesis have appeared to be a promising direction. However, the current hydrogels for VML repair hardly achieve these two goals simultaneously due to their insufficient functionality and the challenge in high-cost of bioactive factors. In this study, a facile strategy using Nb₂C MXene-functionalized hydrogel (OPTN) as a bioactive scaffold is proposed to promote VML repair with skeletal muscle regeneration and functional restoration. In vitro experiments show that OPTN scaffold can effectively scavenge reactive oxygen species (ROS), guide macrophages polarization toward M2 phenotype, and resist bacterial infection, providing a favorable microenvironment for myoblasts proliferation as well as the endothelial cells proliferation, migration, and tube formation. More importantly, OPTN scaffold with electroactive feature remarkably boosts myoblasts differentiation and mesenchymal stem cells neural differentiation. Animal experiments further confirm that OPTN scaffold can achieve a prominent structure-functional VML repair by attenuating ROS levels, alleviating inflammation, reducing fibrosis, and facilitating angiogenesis, newborn myotube formation, and neurogenesis. Collectively, this study provides a highly promising and effective strategy for the structure-functional VML repair through designing bioactive multifunctional hydrogel with microenvironment remodeling and enhanced neurogenesis.