Photobiomodulation therapy in the management of chronic wounds: From molecular mechanisms to translational clinical evidence.

Abstract

Chronic wounds, including diabetic, venous ulcers, pressure injuries, and severe burns, impose a major burden on patient quality of life and healthcare systems worldwide. Persistent disparities in wound care highlight the need for novel, effective, and affordable therapeutic interventions. Photobiomodulation therapy (PBMT), using red and near-infrared light, has emerged as an effective non-pharmacological, non-thermal, and painless approach to enhance wound repair and other inflammatory-mediated ailments. Despite growing evidence of its therapeutic potential, literature remains fragmented with insufficient integration of molecular insights with clinical outcomes, while heterogeneity in dosimetric protocols limits the clinical translation. Therefore, this review provides a critical and integrated overview of the underlying molecular mechanisms and therapeutic applications of PBMT in wound healing through a comprehensive analysis of literature. PBMT primarily operates via mitochondrial photostimulation and downstream signaling cascades involving reactive oxygen species, nitric oxide, calcium flux, bioenergetic activations, redox modulation, and key regulatory pathways, including MAPK/ERK, Wnt/β-catenin, JAK/STAT, PI3K/AKT, and TGF-β/Smad. These pathways collectively influence tissue repair process, including cellular proliferation, neovascularization, immunomodulatory response, and extracellular matrix remodeling, thereby promoting fibroblast activation, keratinocyte migration, collagen deposition, and tissue regeneration. Systematic clinical evidence suggests that PBMT delivered via lasers or LEDs in the visible and near-infrared range with optimum irradiation dosages (450-950 nm, 2-20 J/cm2, 10-500 mW/cm2, continuous/pulsed/superpulsed modes) can significantly improve healing outcomes across diverse wound types by accelerating wound closure, enhancing collagen synthesis, reducing inflammation, and relieving pain. Overall, PBMT is emerging as a safe, non-invasive, cost-effective, and clinically promising photostimulating approach for chronic wounds.