Molecular hydrogen promotes wound healing by inducing early epidermal stem cell proliferation and extracellular matrix deposition.

Abstract

Using a cutaneous aseptic wound model, this study examined the effects of 66% H2 inhalation on wound repair through gene enrichment analysis, spatial profiling, metabolomics, flow cytometry, and live-cell imaging. By day 11 post-wounding, the H2 group exhibited a healing rate approximately 3-fold higher than controls. This acceleration was independent of oxygen supply or reactive oxygen species scavenging. Within 3 days of wounding, enhanced deposition of extracellular matrix components—including dermal collagen-I, epidermal collagen-III, and dermis-epidermis-junction collagen-XVII—was detected in the proximal wound area. H2 also advanced epidermal stem cell proliferation by 1–2 days and promoted their differentiation into myoepithelial cells, which further contributed to ECM deposition. Additional findings included sustained moist healing conditions, improved vascularization, reduced Th1/Th17-associated systemic inflammation, and enhanced tissue remodeling. Mitochondrial function maintenance was proposed as a contributing mechanism.

Mechanism

H2 promotes early proliferation of epidermal stem cells and their differentiation into myoepithelial cells, driving early deposition of collagen-I, -III, and -XVII in the wound area. Maintenance of baseline mitochondrial function is proposed to underlie enhanced cell viability across multiple cell types.