Thiol-mediated ROS-responsive hydrogel with arginine-driven NO cascade for colitis treatment

NO generation to trigger a therapeutic cascade. Specifically, the TPA-derived thiol moieties facilitate inflammation-targeted mucoadhesion via disulfide exchange with the mucosal layer, while simultaneously providing potent, direct ROS scavenging (72.21 ± 2.47% DPPH· radical scavenging). Furthermore, the metabolic byproducts of the hydrogel network provide prebiotic support to restore microbial equilibrium. In a DSS-induced murine colitis model, oral administration of ODCAS significantly attenuated disease severity, reducing the DAI by 52.08%, downregulating pro-inflammatory cytokines, and restoring both intestinal barrier integrity and microbial homeostasis. These findings highlight the ODCAS hydrogel as a robust, ROS-responsive biomaterial platform that orchestrates disulfide-mediated anchoring and an arginine-driven NO cascade for the effective management of chronic inflammatory diseases.