Hydrogen-Enriched Hyaluronic Acid Dressing Ameliorates Diabetic Foot Ulcer via Promoting Mitophagy

Diabetic foot ulcer (DFU) is one of the most common chronic complications of diabetes. This study developed a hydrogen-enriched hyaluronic acid (HA) dressing and aimed to explore its therapeutic effects and mechanisms in DFU treatment.

A combination of vacuum-assisted closure (VSD) and hydrogen-rich saline was used to treat DFU patients and assess the clinical outcomes of wound repair. A rat model of DFU was established, and treatment with hydrogen-enriched HA dressing. Subsequently, the protective effects of the dressing were evaluated, including histological studies, the expression of inflammatory factors and angiogenesis markers. Western blot was used to analyze the expression levels of mitophagy-related proteins. In vitro, the role of HA and hydrogen on cell mitochondrial damage, apoptosis, migration, and markers associated with mitophagy pathways in human foreskin fibroblast-1 (HFF-1) was assessed.

VSD combined with hydrogen-rich saline significantly enhanced wound healing in patients, while reducing inflammation and oxidative damage. In vivo studies showed that the dressing promoted wound healing, increased collagen deposition, reduced inflammatory cytokines, and enhanced neovascularization. In vitro studies, high glucose induced cell morphological damage and oxidative stress, disrupted mitochondrial membrane potential, leading to apoptosis and attenuating cell migration. However, both HA and hydrogen significantly induced SIRT3 expression and activated the downstream FOXO3A/PINK1-PARKIN signaling pathway, promoting mitochondrial autophagy and reducing cell apoptosis. Furthermore, the SIRT3/SOD2 pathway was also activated, decreasing reactive oxygen species (ROS) production and enhancing migration.

This study confirmed that the hydrogen-enriched HA dressing has the potential to enhance diabetic wound repair.