Nanoenzyme-Reinforced Multifunctional Scaffold Based on Ti₃C₂Tx MXene Nanosheets for Promoting Structure-Functional Skeletal Muscle Regeneration via Electroactivity and Microenvironment Management

The completed volumetric muscle loss (VML) regeneration remains a challenge due to the limited myogenic differentiation as well as the oxidative, inflammatory, and hypoxic microenvironment. Herein, a 2D Ti₃C₂Tx MXene@MnO₂ nanocomposite with conductivity and microenvironment remodeling was fabricated and applied in developing a multifunctional hydrogel (FME) scaffold to simultaneously conquer these hurdles. Among them, Ti₃C₂Tx MXene with electroconductive ability remarkably promotes myogenic differentiation via enhancing the myotube formation and upregulating the relative expression of the myosin heavy chain (MHC) protein and myogenic genes (MyoD and MyoG) in myogenesis. The MnO₂ nanoenzyme-reinforced Ti₃C₂Tx MXene significantly reshapes the hostile microenvironment by eliminating reactive oxygen species (ROS), regulating macrophage polarization from M1 to M2 and continuously supplying O₂. Together, the FME hydrogel as a bioactive multifunctional scaffold significantly accelerates structure-functional VML regeneration in vivo and represents a multipronged strategy for the VML regeneration via electroactivity and microenvironment management.