Engineering carboxymethyl chitosan/dialdehyde starch hydrogel as a therapeutic platform for immuno-microbial modulation in ulcerative colitis

Ulcerative colitis (UC) is a chronic inflammatory bowel disorder characterized by mucosal barrier disruption, dysregulated immune activation, and microbial dysbiosis. However, current therapies are limited by systemic toxicity, poor retention at inflamed sites, and insufficient promotion of mucosal healing. Here, we engineered an injectable and self-healing hydrogel via dynamic Schiff base cross-linking between carboxymethyl chitosan (CMCS) and dialdehyde starch (DAS), loaded with dexamethasone (DEX) for localized anti-inflammatory delivery. The resulting CMCS/DAS hydrogel exhibited excellent biocompatibility, robust tissue adhesion, and mechanical resilience, which are crucial for ensuring sustained DEX release and reliable retention in the dynamic colonic environment. In vitro , the hydrogel demonstrated pronounced immunomodulatory efficacy through the promotion of macrophage polarization. In a TNBS-induced rat model of UC, the hydrogel treatment significantly attenuated inflammation, promoted epithelial integrity and barrier repair, and effectively rebalanced gut microbiota composition by enriching beneficial commensals. This multifunctional platform simultaneously addresses the central pathological processes of UC and provides a promising strategy for achieving durable therapeutic remission.