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)/Ga 3+ (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.