In situ Injectable Tetra-PEG Hydrogel Bioadhesive for Sutureless Repair of Gastrointestinal Perforation†

Abstract

Hydrogel bioadhesives represent promising and efficient alternatives to sutures or staples for gastrointestinal (GI) perforation management. However, several concerns remain for the existing bioadhesives including slow and/or weak adhesive, poor mechanical strength, low biocompatibility, and poor biodegradability, which largely limit their clinical application in GI perforation repair. In this work, we introduce an in situ injectable Tetra-PEG hydrogel bioadhesive (SS) composed of tetra-armed poly(ethylene glycol) amine (Tetra-PEG-NH2) and tetra-armed poly(ethylene glycol) succinimidyl succinate (Tetra-PEG-SS) for the sutureless repair of GI defects. The SS hydrogel exhibits rapid gelation behavior and high burst pressure and is capable of providing instant robust adhesion and fluid-tight sealing in the ex vivo porcine intestinal and gastric models. Importantly, the succinyl ester linkers in the SS hydrogel endow the bioadhesive with suitable in vivo degradability to match the new GI tissue formation. The in vivo evaluation in the rat GI injured model further demonstrates the successful sutureless sealing and repair of the intestine and stomach by the SS hydrogel with the advantages of neglectable postsurgical adhesion, suppressed inflammation, and enhanced angiogenesis. Together, our results support potential clinical applications of the SS bioadhesive for the high-efficient repair of GI perforation.