Multispectral Pulsed Photobiomodulation Enhances Re-Epithelialization via Keratinocyte Activation in Full-Thickness Skin Wounds

Abstract

Chronic wound healing is a complex and tightly regulated process requiring coordinated epithelial and stromal regeneration. Photobiomodulation (PBM) using low-level red light-emitting diode (LED) therapy has emerged as a non-invasive approach to enhancing skin repair. In this study, we evaluated the therapeutic efficacy of a pulsed, multi-wavelength LED system on full-thickness excisional wound healing in a normal murine model. Daily LED treatment significantly accelerated wound closure, promoted re-epithelialization, and improved dermal architecture. Histological and immunohistochemical analyses revealed enhanced epidermal stratification, reduced inflammation, and improved collagen organization. Molecular profiling demonstrated increased expression of proliferation marker Ki67, keratins CK14 and CK17, and extracellular matrix-related genes including MMPs, Col1a1, and Col3a1. In vitro assays using HaCaT keratinocytes showed accelerated scratch wound closure and cytoskeletal remodeling following PBM exposure. These findings suggest that pulsed PBM promotes coordinated epithelial regeneration and matrix remodeling, highlighting its potential as a tunable and effective therapeutic modality for accelerating cutaneous wound healing under physiological conditions.