Extracellular matrix in skeletal muscle injury and atrophy: mechanisms and therapeutic implications.

Extracellular matrix (ECM) is an intricate, dynamic network that is essential for structural and biochemical support of skeletal muscle cells. Upon skeletal muscle injury, ECM undergoes rapid remodeling to clear damaged tissue and provides a scaffold to support muscle regeneration. Disruptions in the structure and composition of ECM lead to fibrosis and impaired muscle function, consequently hindering the regenerative capability of skeletal muscle following acute injury. Besides, dysregulation of ECM can also affect muscle mass and cross-sectional area, contributing to the onset of muscle atrophy. Thus, understanding the physiological and mechanical roles of ECM in skeletal muscle injury and atrophy is crucial for developing strategies to treat muscle-related diseases. This review focuses on the complex interactions between the ECM and skeletal muscle, aiming to summarize the regulatory function and mechanism of ECM in muscle development, injury repair, and atrophy. Additionally, it covers recent advances in the treatment of skeletal muscle diseases via the utilization or modulation of ECM components. We will discuss the potential benefits of ECM-based therapies and the current challenges in this area, including producing standardized ECM, minimizing graft-versus-host disease (GVHD), and ensuring that scaffolds have the appropriate biological function. In sum, this comprehensive review will provide a foundation and insights into the relationship between ECM and skeletal muscle, shedding light on the development of ECM-based therapies in the treatment of muscle injury and atrophy. The Translational Potential of This Article: This article systematically explores the regulatory function and mechanism of ECM in muscle development, injury repair, and atrophy. It also summarizes recent advances in therapeutic strategies for skeletal muscle injury and atrophy from the ECM perspective. Insights from this review contribute to the development of therapeutic strategies for skeletal muscle injury and atrophy by modulating or utilizing ECM components, thus providing novel therapeutic avenues for tissue engineering and regenerative medicine approaches to muscle-related disorders.