Hydrogel-Based Artificial Mucosa Restores Local Immune and Microbial Homeostasis for Treating Ulcerative Colitis

Ulcerative colitis (UC) is a common inflammatory bowel disease driven by the dyshomeostasis of intestinal immune system and microbiota, but its treatment options are limited due to impaired epithelial barrier integrity and function. Herein, a multifunctional biomimetic hydrogel is developed as artificial colonic mucosa, which can readily establish a bioadhesive barrier at the ulcer site and restore local immune and microbial homeostasis to exert potent anti-inflammatory effect. The hydrogel framework is generated through the thrombin-mediated activation and polymerization of fibrinogen that resembles natural blood coagulation mechanism. During this process, the antibacterial agent Ag+ is used for the crosslinking between the generated fibrin units and dopamine/thiol-modified hyaluronic acid biopolymers via Ag+-thiol coordination to convey enhanced bioadhesiveness, while the interconnected porous network is employed to encapsulate basic fibroblast growth factor (bFGF) and alanyl-glutamine (ALG) for mucosa regeneration. The hydrogel stably adheres to the ulcer site to protect and repair the damaged epithelium and establishes an anti-inflammatory microenvironment by inducing locoregional M1-to-M2 macrophage repolarization while eliminating harmful gut flora, which can act in a cooperative manner to substantially alleviate UC symptoms. The biomimetic hydrogel here presents a promising approach for effective UC therapy in the clinics.

Automated summary

A multifunctional biomimetic hydrogel, resembling natural blood coagulation mechanism, is developed to treat ulcerative colitis (UC). The hydrogel acts as an artificial colonic mucosa, forming a bioadhesive barrier at the ulcer site and restoring immune and microbial homeostasis. This hydrogel presents a promising approach for effective UC therapy.