Boron-complexed oxidized dextran/carboxymethyl chitosan hydrogel loaded with paeoniflorin alleviates UC via TLR4-NF-κB pathway regulation and intestinal mucosal barrier restoration

Ulcerative colitis (UC) is a chronic relapsing inflammatory bowel disease characterized by large-intestinal mucosal ulceration and persistent inflammation, which manifests as bloody diarrhea and abdominal pain and may elevate colorectal cancer risk. Polysaccharide-based hydrogels are attractive candidates for local rectal therapy of UC owing to favorable biocompatibility; however, their therapeutic performance is compromised by short lesion residence time caused by continuous intestinal peristalsis. Herein, we fabricated a muco-adaptive multifunctional hydrogel (B-ODT/CM@PF) constructed via dual-dynamic cross-linking of boronate-diol ester bonds and Schiff-base imine bonds for local treatment of UC. The carboxymethyl chitosan component contributes to rapid local hemostasis and epithelial barrier repair, whereas boron-complexed oxidized dextran confers broad-spectrum bactericidal capacity by disrupting bacterial membrane integrity. Benefiting from boronate-diol interactions, paeoniflorin (PF) is anchored within hydrogel networks to realize inflammation-triggered sustained release. The released PF targets the TLR4-NF-κB signaling axis to drive macrophage M2 polarization and mitigate excessive intestinal inflammatory responses. Moreover, B-ODT/CM@PF rescues the integrity of the intestinal mucosal barrier by inhibiting MLCK activation and preserving tight-junction proteins expression, further ameliorating colitis manifestations. Collectively, this dual-crosslinked bioadhesive hydrogel achieves synergistic functions including mucosal adhesion, hemostasis, antibacterial activity, immunomodulation and barrier reconstruction, providing a promising strategy for local treatment of UC.