Photobiomodulation for skeletal muscle regeneration: mechanisms, dosimetry, and translational challenges.

Photobiomodulation (PBM) has gained increasing attention as a non-invasive modality for enhancing skeletal muscle recovery; however, its clinical translation remains limited by inconsistencies in dosimetry, methodology, and reporting across studies. This review synthesizes over two decades of preclinical and clinical research to evaluate how key parameters such as wavelength, irradiance, fluence, pulse structure, and timing affect muscle regeneration. Evidence indicates that red and near-infrared light modulate mitochondrial cytochrome c oxidase activity, promoting nitric oxide dissociation, increasing ATP production, and inducing controlled reactive oxygen species (ROS) signaling that supports satellite cell activation, angiogenesis, and anti-inflammatory responses. These effects follow a biphasic dose-response relationship and are strongly influenced by tissue optical properties, which differ significantly between animal models and humans, contributing to variability in clinical outcomes. This review highlights critical challenges, including uncertainties in light delivery and tissue-level dose deposition. This review outlines recommendations to improve reproducibility, including standardized dosimetry, radiometric calibration, and integration of PBM with exercise-based rehabilitation. Emerging approaches, such as Monte Carlo light transport modeling and patient-specific optical simulations, are discussed as promising strategies for personalized treatment planning. Collectively, these advances support the transition of PBM from an empirical intervention toward a mechanistically guided and clinically reliable therapy for skeletal muscle regeneration.