Endoscopic Delivery of a Double-Umbrella-Shaped Hydrogel Occluder with Instant Mechanical Interlock and Robust Wet Adhesion for Gastric Perforation Repair

Abstract

Achieving robust adhesion of bioadhesives on wet tissues to block gastric perforation remains a challenge due to the gradually deteriorated adhesive-tissue interactions by interfacial acidity and multienzyme gastric fluids, thus accompanying failure shedding and life-threatening risks. Here, we report a biocompatible double-umbrella-shaped endoscopy-deliverable hydrogel occluder (EHO) made of caffeic acid (CA)-grafted chitosan (CS) and polyacrylamide (PAM) by molding technique, which is capable of the customizable, rapid, robust, and long-term sealing of large gastric perforations. In addition to interfacial physiochemical interactions (e.g., H-bonding, chelation) between the tissues and polymers, efficient sealing also integrates the advantages of fast mechanical interlocking in space and gradual self-expansion over time to tolerant acidic and mechanically dynamic environments. The EHO exhibits favorable biodegradability due to the reducible disulfide cross-linkers and remarkable protective barrier functions to impede the infiltration of gastric acid and digestive pepsin into the wound. To validate EHO's therapeutic efficacy, we further demonstrate the robust in vivo sealing to large gastric tissues via endoscopic delivery to the porcine stomach and monitor of healing process with improved retention of endogenous growth factors. Besides, in views of simple hydrogel fabrication using molding technique, the biodegradable EHO can be facilely tailored with various topologies according to application scenarios in surgical and minimally invasive endoscopic delivery, thus offering a promising alternative for clinical repair of gastrointestinal perforations and other organs.

Keywords: endoscopic delivery; gastric perforation; hydrogel occluder; mechanical interlock; wound healing.