Nanoenzyme-Reinforced Multifunctional Scaffold Based on TiCTx MXene Nanosheets for Promoting Structure-Functional Skeletal Muscle Regeneration via Electroactivity and Microenvironment Management. Nano letters 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 TiCTx MXene@MnO nanocomposite with conductivity and microenvironment remodeling was fabricated and applied in developing a multifunctional hydrogel (FME) scaffold to simultaneously conquer these hurdles. Among them, TiCTx 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 MnO nanoenzyme-reinforced TiCTx MXene significantly reshapes the hostile microenvironment by eliminating reactive oxygen species (ROS), regulating macrophage polarization from M1 to M2 and continuously supplying O. Together, the FME hydrogel as a bioactive multifunctional scaffold significantly accelerates structure-functional VML regeneration and represents a multipronged strategy for the VML regeneration via electroactivity and microenvironment management. 10.1021/acs.nanolett.3c01784

Highly Aligned Ternary Nanofiber Matrices Loaded with MXene Expedite Regeneration of Volumetric Muscle Loss. Nano-micro letters Current therapeutic approaches for volumetric muscle loss (VML) face challenges due to limited graft availability and insufficient bioactivities. To overcome these limitations, tissue-engineered scaffolds have emerged as a promising alternative. In this study, we developed aligned ternary nanofibrous matrices comprised of poly(lactide-co-ε-caprolactone) integrated with collagen and TiCT MXene nanoparticles (NPs) (PCM matrices), and explored their myogenic potential for skeletal muscle tissue regeneration. The PCM matrices demonstrated favorable physicochemical properties, including structural uniformity, alignment, microporosity, and hydrophilicity. In vitro assays revealed that the PCM matrices promoted cellular behaviors and myogenic differentiation of C2C12 myoblasts. Moreover, in vivo experiments demonstrated enhanced muscle remodeling and recovery in mice treated with PCM matrices following VML injury. Mechanistic insights from next-generation sequencing revealed that MXene NPs facilitated protein and ion availability within PCM matrices, leading to elevated intracellular Ca levels in myoblasts through the activation of inducible nitric oxide synthase (iNOS) and serum/glucocorticoid regulated kinase 1 (SGK1), ultimately promoting myogenic differentiation via the mTOR-AKT pathway. Additionally, upregulated iNOS and increased NO contributed to myoblast proliferation and fiber fusion, thereby facilitating overall myoblast maturation. These findings underscore the potential of MXene NPs loaded within highly aligned matrices as therapeutic agents to promote skeletal muscle tissue recovery. 10.1007/s40820-023-01293-1

Skeletal muscle regeneration with 3D bioprinted hyaluronate/gelatin hydrogels incorporating MXene nanoparticles. International journal of biological macromolecules There has been significant progress in the field of three-dimensional (3D) bioprinting technology, leading to active research on creating bioinks capable of producing structurally and functionally tissue-mimetic constructs. TiCT MXene nanoparticles (NPs), promising two-dimensional nanomaterials, are being investigated for their potential in muscle regeneration due to their unique physicochemical properties. In this study, we integrated MXene NPs into composite hydrogels made of gelatin methacryloyl (GelMA) and hyaluronic acid methacryloyl (HAMA) to develop bioinks (namely, GHM bioink) that promote myogenesis. The prepared GHM bioinks were found to offer excellent printability with structural integrity, cytocompatibility, and microporosity. Additionally, MXene NPs within the 3D bioprinted constructs encouraged the differentiation of C2C12 cells into skeletal muscle cells without additional support of myogenic agents. Genetic analysis indicated that representative myogenic markers both for early and late myogenesis were significantly up-regulated. Moreover, animal studies demonstrated that GHM bioinks contributed to enhanced regeneration of skeletal muscle while reducing immune responses in mice models with volumetric muscle loss (VML). Our results suggest that the GHM hydrogel can be exploited to craft a range of strategies for the development of a novel bioink to facilitate skeletal muscle regeneration because these MXene-incorporated composite materials have the potential to promote myogenesis. 10.1016/j.ijbiomac.2024.130696

Bioactive MXene Promoting Angiogenesis and Skeletal Muscle Regeneration through Regulating M2 Polarization and Oxidation Stress. Advanced healthcare materials Complete repair of skeletal muscles caused by severe mechanical damage and muscle-related diseases remains a challenge. 2D Ti C T (MXene) possesses special photoelectromagnetic properties and has attracted considerable attention in materials science and engineering. However, the bioactive properties and potential mechanism of MXene in tissue engineering, especially in skeletal muscle regeneration, are unclear. Herein, the antioxidation and anti-inflammation activities of MXene and its effects on myogenic differentiation and regeneration of skeletal muscle in vivo are investigated. In vitro studies have shown that MXene has excellent antioxidation and anti-inflammatory properties, and promotes myogenic differentiation and angiogenesis. MXene can remove excess reactive oxygen species in macrophage cells to alleviate oxidative stress and induce the transformation of M1 macrophages into M2 macrophages to reduce excessive inflammation, which can significantly promote the proliferation and differentiation of myoblasts, as well as the proliferation, migration, and tube formation of endothelial cells. Animal experiments with rat tibial anterior muscle defects show that MXene can promote angiogenesis, muscle fiber formation, and skeletal muscle regeneration by regulating the cell microenvironment through anti-inflammatory and antioxidant pathways. The findings suggest that MXene can be used as a multifunctional bioactive material to enhance tissue regeneration through robust antioxidation, anti-inflammation, and angiogenesis activities. 10.1002/adhm.202201862