S-nitrosoglutathione releasing nano-micron combination hydrogel enhances cutaneous wound healing via promoting angiogenesis and collagen deposition

Nitric oxide (NO) is essential for wound healing, promoting angiogenesis and collagen deposition. This study investigates a novel dual-matrix nanocomposite hydrogel incorporating S-nitrosoglutathione (GSNO), a physiological NO donor, to enhance cutaneous wound healing. GSNO was encapsulated in ammonio methacrylate copolymer nanoparticles and embedded in an alginate-based matrix, achieving controlled NO release. GSNO-loaded nanoparticles were prepared using solvent displacement and solvent evaporation methods, resulting in spherical, well-distributed and positively charged particles. These nanoparticles were cross-linked with negatively charged alginic acid to form a nanocomposite hydrogel. The hydrophobic nanoparticles protected GSNO from degradation, while the hydrophilic alginate matrix sustained the release of active GSNO for up to 10 h, promoting haemostasis and maintaining a moist wound environment. The hydrogel exhibited good biocompatibility in human fibroblasts and significantly enhanced wound repair by promoting fibroblast formation, neovascularisation and collagen deposition, as demonstrated by haematoxylin and eosin staining and Masson's trichrome staining. In conclusion, the GSNO-loaded nanocomposite hydrogel significantly accelerated the healing process by enhancing angiogenesis and collagen deposition, offering a promising strategy for improving wound healing.