An endoscopy deliverable hydrogel dry powder for sealing and repairing gastric perforation.

Abstract

Gastric perforation (GP) is characterized by full-thickness injury of the stomach wall, a severe and potentially life-threatening gastrointestinal disease. However, current treatment, including surgical sutures and endoscopic closure, faces limitations, achieving complete sealing of the perforation and favorable healing remains a great challenge and an acute clinical demand. Here, we report a hydrogel dry powder (PPCL@Mg) for the minimally invasive treatment of GP, which can be delivered to target perforation wounds by spraying via an endoscope, and rapidly absorbing interfacial water and spontaneously forming a hydrogel. This hydrogel was designed with strong adhesion, gastric fluid resistance, good anti-swelling behavior, biocompatibility, anti-oxidation, anti-inflammatory and hemostatic properties, which forms instant, robust and sutureless sealing of GP. In vivo rat GP model results indicated that PPCL@Mg hydrogel effectively sealed the perforation and accelerated healing by promoting cell proliferation and angiogenesis, and regulating inflammation and oxidative stress, and the therapeutic effect surpassed that of surgical suture. Furthermore, the large animal pig GP model further validated the repair efficacy of the PPCL@Mg powder and revealed its superior sealing and repair efficacy compared to titanium clips. Transcriptome sequencing and proteomics analysis further verified the significant therapeutic outcomes and elucidated its mechanism in promoting perforation healing. The proposed PPCL@Mg hydrogel dry powder provides a promising therapeutic approach for GP repair and demonstrates significant clinical translational potential. STATEMENT OF SIGNIFICANCE: As one of the most severe gastrointestinal emergencies, gastric perforation (GP) poses a significant clinical challenge, where reliable perforation sealing and healing are urgently needed. In this work, we introduce PPCL@Mg, a hydrogel dry powder for minimally invasive GP treatment. Delivered endoscopically via spraying, it rapidly absorbs water and spontaneously forms an adhesive hydrogel. Engineered with strong adhesion, gastric-fluid resistance, anti-swelling, biocompatibility, anti-oxidation, anti-inflammatory and hemostatic properties, this hydrogel enables instant, robust, sutureless GP sealing. In vivo rodent and porcine models demonstrated PPCL@Mg hydrogel's efficacy in sealing gastric perforations and accelerating healing. This dry powder system presents a promising strategy for GP repair with significant translational potential.