Multifunctional hydrogel assembled from phenylboronic acid-chitosan and Polygonati Rhizoma polysaccharide for accelerated radiation-combined wound healing.

Abstract

Combined radiation-wound injury (CRWI) is difficult to heal because of persistent oxidative stress, inflammation, and impaired angiogenesis. Herein, a multifunctional pH and reactive oxygen species (ROS)-responsive hydrogel was prepared by dynamic crosslinking of Polygonati Rhizoma-derived polysaccharide fraction (PC) with phenylboronic acid-modified chitosan (CS-BA) through reversible boronate ester bonds. The obtained PC/CS-BA hydrogel was injectable and exhibited tissue adhesion, self-healing ability, and pH/ROS-responsive network disassembly. The optimized PC/CS-BA-1 hydrogel showed favorable mechanical stability and broad-spectrum antioxidant activity against O2•-, ABTS•, PTIO•, and •OH radicals. In addition, the hydrogel displayed excellent in vitro hemocompatibility and cytocompatibility, effectively reduced irradiation-induced intracellular ROS accumulation, and inhibited cell apoptosis. In a mouse model combining a full-thickness dorsal wound with local irradiation, the hydrogel significantly accelerated wound closure, achieving 81.1% healing on day 7 and nearly complete closure on day 14. Histological analyses further confirmed improved epidermal regeneration, collagen remodeling, skin appendage formation, and angiogenesis. Overall, this PC/CS-BA hydrogel provides a responsive and bioactive wound dressing strategy for radiation-combined wound repair.