Mucin-Based Injectable Hydrogel Loaded with Resolvin E1 for Rectal Mucosal Repair after Endoscopic Submucosal Dissection.

Abstract

Endoscopic submucosal dissection (ESD), while a gold-standard minimally invasive technique for treating early-stage intestinal cancers, poses significant challenges for postoperative mucosal repair, owing to the risk of complications such as bleeding, perforation, and infection. Existing strategies often fail to provide a bioactive healing microenvironment. This study presents a Resolvin E1 (RvE1)-loaded, mucin-based injectable hydrogel (MHSR) designed to address these limitations. Employing a component-based biomimetic approach, this hydrogel combines thiol-modified mucin (MUC-S) with zwitterionic methacrylated hyaluronic acid (HA-SB-MA) via thiol-ene click chemistry. The MHSR hydrogel demonstrates good injectability, self-healing properties, and adhesion to positively charged inflamed tissues via electrostatic interactions and disulfide bonds. It establishes a strong physical barrier that effectively resists biofouling from proteins, cells, and bacteria. Notably, MHSR orchestrates comprehensive mucosal regeneration by scavenging reactive oxygen species (ROS), modulating inflammatory responses, enhancing angiogenesis, restoring tight junction integrity, normalizing goblet cell function, and regulating gut microbiota. In the rat model of rectal ESD, MHSR significantly accelerated wound closure, reduced inflammation, and promoted functional restoration of the mucosal barrier. This multifunctional hydrogel system constitutes a highly promising biomimetic strategy for promoting mucosal repair and remodeling of the intestinal microenvironment after ESD. STATEMENT OF SIGNIFICANCE: The study reports a mucin-based injectable hydrogel (MHSR) loaded with Resolvin E1 for rectal mucosal repair after endoscopic submucosal dissection. It combines thiol-modified mucin and zwitterionic hyaluronic acid to form an adhesive, self-healing barrier with anti-biofouling properties. The hydrogel scavenges reactive oxygen species, modulates inflammation, promotes angiogenesis, restores mucosal integrity, and regulates gut microbiota. It significantly accelerates wound healing and reduces complications in a rat ESD model, offering a promising strategy for post-operative regenerative therapy.