Natural deep eutectic solvents (NADES)-based chitosan hydrogel for enhanced photoimmunomodulation treatment on various wounds.

Natural Deep Eutectic Solvents (NADES) have recently emerged as eco-friendly, biodegradable alternatives to conventional solvents, offering excellent solubility and low toxicity (10 μg/mL). In this study, we developed a novel NADES-chitosan-based hydrogel combined with photoimmunomodulation (PIM) to enhance healing of ulcer-related wounds. The hydrogel exhibited a nanostructured network with globular aggregates (20-50 nm) interacting with amine and alcohol groups, contributing to improved biocompatibility, biodegradability, and thermal stability (50-120 °C and 130-200 °C). Cytotoxicity and permeability assays confirmed the hydrogel's enhanced bioactivity and extraction efficiency. Following PIM treatment, significant wound healing effects were observed, including increased cell migration, improved mitochondrial membrane potential, reduced intracellular ROS, and differential protein expression in AGS and HT29 cells (p < 0.05 and p < 0.01, respectively). These findings highlight the novelty of using NADES as a gelation solvent in hydrogels for wound therapy, with strong translational potential in diabetic and gastric ulcer treatment and scalability in pharmaceutical, food, and nutraceutical industries. Chemical compounds: chitosan, polyvinyl chloride, bentonite, chlorine chloride, lactic acid and malic acid.