Prolonged Nitric Oxide Release from Composite Hydrogels Containing S-Nitroso Glutathione Microparticles for Diabetic Wound Care

Wound dressings play a critical role in preventing infections, maintaining optimal moisture levels, and expediting healing to enhance wound recovery and minimize scarring in diabetic wounds. Impaired diabetic wounds exhibit persistent inflammation, reduced growth factor secretion, and suppressed angiogenesis, resulting in slow and difficult healing. Nitric oxide (NO) plays a vital role in wound healing, but its production is hindered in diabetic wounds under hyperglycemic conditions. This study explores encapsulating NO donors in polymeric hydrogels to enable controlled and prolonged NO release directly into diabetic wounds.In this study, a NO-releasing hydrogel using chitosan (CS) and S-nitroso glutathione (GSNO) as the NO donor was developed. First, GSNO was successfully synthesized, as confirmed by NMR, FTIR, and UV-vis spectroscopy. After that, GSNO was encapsulated into poly(lactic acid) microparticles through the emulsion solvent evaporation technique, with ۶۹% ± ۵% encapsulation efficiency. Scanning electron microscopy verified microparticle formation with the diameter of ۵.۲ ± ۲.۷ μm. The microparticles were then incorporated into CS hydrogels, synthesized by ionic gelation, to provide prolonged NO release. FTIR confirmed gel formation, while SEM revealed an average pore size of ۱۵۳ ± ۱۶ μm and uniform microparticle distribution. The hydrogel exhibited a swelling ratio of ۲۲.۷ ± ۴.۱ and a water vapor transmission rate of ۲۲۳۷ ± ۱۸۳ g/m۲/day. In vitro NO release studies over ۱۰ days, quantified by the Griess assay, demonstrated controlled and prolonged NO release. Cytocompatibility assays using human dermal fibroblasts (HDF) confirmed that GSNO directly enhances cell proliferation. Overall, this NO-releasing hydrogel shows promise as an advanced wound dressing to treat diabetic wounds.