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

Area of Science:

• Biomedical Engineering
• Skeletal Muscle Physiology
• Cellular Mechanobiology

Background:

• Skeletal muscle function is crucial for movement and overall health.
• Mechanisms of muscle growth and repair, especially during exercise, require further elucidation.
• Understanding cellular responses to mechanical stimuli is key to muscle health.

Purpose of the Study:

• To develop and validate a microfluidic system for simulating skeletal muscle injury and repair.
• To investigate the cellular and molecular responses to different exercise intensities.
• To provide a platform for studying muscle diseases and developing therapies.

Main Methods:

• Design of a multifunctional microfluidic chip simulating distinct movement modes.
• Induction of muscle injury and repair in situ by modulating device parameters.
• Analysis of myoblast and myotube responses using molecular and imaging techniques.
• Development of a simplified numerical simulation model.

Main Results:

• High-intensity exercise caused myoblast damage and detachment.
• Low-intensity exercise activated mechanosensitive ion channels (Piezo1) and upregulated adhesion proteins (Talin1).
• Regenerated myotubes showed organized actin-myosin filaments, enhanced myogenic gene expression, and longitudinal fusion.

Conclusions:

• The microfluidic system effectively models exercise-induced muscle injury and repair.
• Low-intensity exercise promotes skeletal muscle regeneration and maturation through specific mechanotransduction pathways.
• This platform offers a novel approach for skeletal muscle disease modeling and therapeutic development.