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

Thecompleted volumetric muscle loss (VML) regeneration remainsa challenge due to the limited myogenic differentiation as well asthe oxidative, inflammatory, and hypoxic microenvironment. Herein,a 2D Ti(3)C(2)Tx MXene@MnO2 nanocompositewith conductivity and microenvironment remodeling was fabricated andapplied in developing a multifunctional hydrogel (FME) scaffold tosimultaneously conquer these hurdles. Among them, Ti(3)C(2)Tx MXene with electroconductive ability remarkably promotesmyogenic differentiation via enhancing the myotube formation and upregulatingthe relative expression of the myosin heavy chain (MHC) protein andmyogenic genes (MyoD and MyoG) in myogenesis. The MnO2 nanoenzyme-reinforcedTi(3)C(2)Tx MXene significantly reshapes the hostilemicroenvironment by eliminating reactive oxygen species (ROS), regulatingmacrophage polarization from M1 to M2 and continuously supplying O-2. Together, the FME hydrogel as a bioactive multifunctionalscaffold significantly accelerates structure-functional VMLregeneration in vivo and represents a multiprongedstrategy for the VML regeneration via electroactivity and microenvironmentmanagement.