Recent Advances in Stimuli-Responsive Hydrogels for Inflammatory Bowel Disease Therapy

Inflammatory bowel disease (IBD) is a chronic and relapsing gastrointestinal disorder that requires long-term management, while current therapies remain limited by premature drug loss, systemic exposure, and insufficient local retention. Stimuli-responsive hydrogels provide a local delivery platform whose network structure changes in response to gastrointestinal and inflammatory microenvironments, thereby affecting drug protection, retention, and release. This review discusses hydrogel network transitions, crosslinking strategies, and drug-loading approaches, together with the effects of pH, redox conditions, enzymes, inflammatory signals, and temperature on hydrogel behavior. Oral, rectal, and endoscopic delivery are examined in relation to gastrointestinal protection, local retention, mucosal adhesion, and lesion-localized therapy. The therapeutic effects of these systems include epithelial barrier protection and repair, regulation of oxidative stress and immune responses, modulation of the gut microbiota, and mucosal regeneration. Differences in gastrointestinal and inflammatory environments are also considered in relation to hydrogel response, local drug delivery, and long-term performance. Furthermore, the existing bottlenecks restricting their clinical translation are highlighted, and feasible directions for the follow-up optimization of responsive hydrogel systems for IBD treatment are prospected.