Acid-Triggered Charge-Switchable Antibacterial Hydrogel for Accelerated Healing of Gastric Mucosal Wounds

Infection with <i>Helicobacter pylori</i> (<i>H. pylori</i>) is a primary etiological factor for chronic gastritis, peptic ulcers, and gastric cancer. The limited specificity of antibiotics against <i>H. pylori</i>, combined with the risk of severe adverse events from endoscopic submucosal dissection (ESD), presents a major global health challenge in treating gastric mucosal injuries. To address this issue, we developed a targeted antibacterial hydrogel based on a charge-reversal amphiphilic molecule, designed for the harsh gastric acid environment and capable of immediate and strong adhesion. The hydrogel is composed of acryl aspartate (AASP) and cysteine-grafted carboxymethyl chitosan (CMCS-NAC) as the base matrix, integrated with gastric acid-responsive charge-reversal antibacterial molecules (C₁₆N-DCA). Simulated studies show that C₁₆N-DCA undergoes charge reversal under acidic conditions (pH 3), enabling targeted <i>H. pylori</i> eradication mediated by gastric acid, with 98% efficacy and sustained antibacterial activity for up to 36 h. In vitro and in vivo experiments in rodent and porcine models confirmed its safety and efficacy in acidic gastric conditions. This hydrogel offers strong tissue protection and effectively modulates the gastric wound microenvironment, facilitating wound healing and presenting an easily adoptable solution for gastric wound management.