Poly glycerol sebacate/poly lactide acid (PGS/PLA) hydrogel in combination with hyperbaric oxygen therapy improved full thickness wound healing in diabetic rat

Abstract

Chronic wounds, particularly in diabetic patients, pose significant therapeutic challenges due to impaired healing under ischemic conditions. This study investigated the synergistic effect of a poly glycerol sebacate/poly lactide acid (PGS/PLA) hydrogel combined with hyperbaric oxygen therapy (HBOT) on wound healing in a diabetic rat model. Full-thickness skin wounds were induced on the dorsum of rats and treated with PGS/PLA, HBOT, or their combination. Histological evaluations were performed using stereological techniques to quantify fibroblasts, neutrophils, and blood vessels. Collagen content was assessed by Masson's trichrome staining. Wound tensile strength, oxidative stress biomarkers (GSH, SOD, CAT, MDA), and expression levels of related genes (TGF-β, VEGF, bFGF, HIF-1α, TNF-α, IL-1β) were also analyzed. The results showed that the PGS/PLA+HBOT group significantly improved wound closure, increased fibroblast density, and reduced neutrophil count compared to other groups (p < 0.05). Vascular density and collagen deposition were highest in the combined treatment group (p < 0.05). Biomechanical analysis revealed enhanced tensile strength in all treated groups, with the combination group outperforming the others (p < 0.05). Antioxidant levels were significantly elevated, while MDA levels were decreased, particularly in the PGS/PLA+HBOT group (p < 0.05). Gene expression analysis showed increased levels of TGF-β, VEGF, and bFGF, and reduced expression of HIF-1α, TNF-α, and IL-1β in treated wounds (p < 0.05). The combination of PGS/PLA nanofiber dressing with HBOT effectively accelerates wound healing by enhancing cellular proliferation, angiogenesis, collagen formation, redox balance, and modulation of inflammatory and regenerative gene expression. This strategy may offer a promising therapeutic approach for managing ischemic wounds.

Keywords: Diabetes; Hydrogel; Hyperbaric oxygen therapy; PGS; PLA; Wound healing.