Rational design of hydrogels for the intestinal mucosa restoration

Inflammatory bowel disease (IBD), including Crohn’s disease and ulcerative colitis, is characterized by gut dysbiosis, impaired mucus and epithelial barrier integrity, and chronic inflammation and affects 0.3–0.5% of the global population. Current therapies are limited by poor bioavailability and short residence time at the inflamed site, highlighting the need for biomaterials capable of prolonged mucosal delivery and tissue repair. We developed hydrogels based on pectin, which exhibits anti-inflammatory and prebiotic effects, and Aloe Vera juice, internally crosslinked with CaCO₃, for intestinal mucosal restoration and therapeutic delivery. Sodium butyrate was used as a model therapeutic additive. Rheological analyses, including frequency sweep, recovery, and yield-stress tests, were performed to investigate the viscoelastic properties, self-healing behavior, and mucosal retention, respectively. CaCO₃ concentration and Aloe Vera juice pH were identified as key parameters controlling CaCO₃ dissolution and thus the degree of crosslinking. The addition of sodium butyrate did not alter the viscoelastic properties, confirming the suitability of the hydrogel as an active loading matrix. The hydrogels recovered their mechanical properties after repeated stimuli and exhibited yield stress values exceeding intestinal luminal shear stresses, supporting mucosal retention and thus their potential for stable mucoadhesion and sustained local therapy in IBD.