ROS-Responsive Dynamic Hydrogel for Gastric Perforation Repair

Gastric perforation repair demands adhesive hydrogels that couple robust sealing with controlled drug release to overcome the challenges of continuous peristalsis and the oxidative wound microenvironment. Herein, we developed a reactive oxygen species (ROS)-responsive dynamic hydrogel formed by incorporating a ROS-cleavable tannic acid-2-formylphenylboronic acid (TA-FPBA) complex into an imine-crosslinked network made of 4-arm polyethylene glycol benzaldehyde (4-arm-PEG-CHO) and ε-poly-L-lysine (ε-PLL) through tandem dynamic iminoboronate and boronate ester bonds, denoted as PEG-PL-TA₁ hydrogel. The hydrogel exhibited rapid in situ gelation (∼64 s), robust tissue adhesion (∼25.7 kilopascal), and sufficient burst pressure (∼128.8 millimeters of mercury) for effective gastric sealing. Upon exposure to elevated ROS levels at the wound site, boronate ester bonds were cleaved to trigger the on-demand release of TA. The released TA demonstrated potent antioxidant activity, protecting gastric epithelial cells from oxidative damage and preserving viability. In vivo outcomes of gastric perforation treatments in rats revealed that the PEG-PL-TA₁ hydrogel synergistically sealed the defect while modulating the wound microenvironment by alleviating oxidative stress and shifting immune balance toward repair, ultimately accelerating perforation repair. Our work provides a promising design strategy for dynamic hydrogels for controlled drug release and offers a potential therapeutic strategy for clinical gastric perforation treatment.