Muscle regeneration on a chip: exercise-induced microtrauma and optimal mechanical stimulation regimen

Abstract

Skeletal muscles, through their coordinated interaction with bones and joints, enable diverse human movements and are essential for maintaining normal physiological functions and overall health. However, the physiological state of skeletal muscles and the mechanisms underlying muscle growth during exercise remain incompletely understood. To address this, we propose a multifunctional microfluidic chip system capable of simulating two distinct modes of movement. By modulating device parameters, this system enables in situ induction of muscle injury and subsequent mechanical repair. Our findings reveal that high-intensity exercise induces myoblast damage and cell detachment. Low-intensity exercise, over time, promotes activation of mechanosensitive ion channels (Piezo1) in myoblasts, upregulation of adhesion proteins (Talin1), cytoskeletal reorganization, and longitudinal myotube fusion along the mechanical stimulation axis. The regenerated myotubes exhibit distinct striations of actin and myosin filaments, accompanied by elevated expression of myogenic genes, indicating maturational development. Furthermore, a simplified numerical simulation model validates the platform's efficacy in studying muscle injury and repair processes. This work provides a novel strategy for future research on skeletal muscle disease modeling and therapeutic development.