Inflammation Targeting‐Triggered Healing Hydrogel for In Situ Reconstruction of Colonic Mucosa

Abstract Inflammatory bowel disease (IBD) is characterized by intestinal mucosal damage that exacerbates inflammation and promotes disease recurrence. Although hydrogel‐based therapies have shown potential for mucosal repair, challenges remain due to inadequate targeting and low hydrogel density, leading to ongoing infiltration of harmful substances and delayed mucosal healing. In this study, an inflammation‐targeting‐triggered healing hydrogel (ITTH hydrogel) is developed, composed of polyvinyl alcohol‐alginate microgels (PALMs) and a cyclodextrin polymer crosslinker (CPC). This hydrogel specifically targets inflamed colonic sites and crosslinks in situ to form a dense network. The results demonstrate that the ITTH hydrogel adheres effectively to inflamed colonic tissue in both IBD mouse models and human samples. The dense crosslinked network acts like the mucosal barrier, preventing the penetration of detrimental substances such as bacteria and small molecules, thereby protecting the underlying mucosal tissue. Furthermore, the ITTH hydrogel significantly improved therapeutic outcomes in mice with dextran sulfate sodium (DSS)‐induced colitis. These findings suggest that the ITTH hydrogel is a promising candidate for in situ reconstruction of colonic mucosa and the treatment of IBD.