A single-step injectable Janus-adhesive hydrogel for endoscopic gastrointestinal fistula repair

Gastrointestinal fistulas (GFs) represent one of the main causes of morbidity and mortality. While endoscopic techniques provide a minimally invasive approach to GF repair, offering advantages over conventional surgical approaches, the integration of endoscopic delivery with hydrogel sealants in user-friendly and easy processes approaches remains a great challenge. Here we develop a thermoresponsive positively charged poly(N-isopropylacrylamide) (PNIPAM)/Ga³⁺ (PGa^III) hydrogel sealant, formed by slug-inspired biomimetic self-assembly. The PGa^III integrated injectability and single-step-formed Janus-type adhesion to tissues, simultaneously featuring excellent biocompatibility, water/acid resistance, active shrinkage and antibacterial properties, enabling its effective ready-to-use biological sealant for endoscopic repair of GFs and prevention of postoperative adhesions. To validate the efficacy of PGa^III in treating GFs, we demonstrate its effectiveness in repairing GFs and its convenience in non-invasive endoscopic surgery in living Sprague-Dawley rat and Bama miniature pig models. The proposed PGa^III holds potential for the repair of fistulas in other organs in vivo, thereby promoting the establishment of safer and more effective clinical treatment options for related diseases.