Evaluation of Genipin-Crosslinked Small Intestinal Submucosa for a Full-Thickness Gastric Defect Repair

Gastrectomy is often associated with serious complications that lack effective treatments. Despite the widespread adoption in tissue engineering, the rapid degradation of small intestinal submucosa (SIS) compromised its performance in gastric tissue engineering. Thereby, genipin, a natural crosslinking agent, was employed to modify SIS, and the potential of genipin-crosslinked SIS (GP-SIS) in promoting the regeneration of full-thickness gastric defects was explored. The data on crosslinking efficiency demonstrated that genipin can efficiently fix SIS. GP-SIS exhibited high resistance against collagenase, enhanced hydrothermal stability, and improved mechanical properties according to in vitro degradation, shrinkage temperature, and uniaxial tensile tests. Additionally, GP-SIS maintained excellent biocompatibility based on a cytotoxicity test and rat subcutaneous implantation. In the rat full-thickness gastric wall defect model, GP-SIS, serving as a protective barrier, accelerated the newly formed granulation tissues and fibrosis, avoiding the occurrence of gastric leakage. Its niche and growth factors further promoted the vascularization and epithelialization of the regenerated area. In conclusion, GP-SIS will be feasible in the near future for gastric wall reconstruction after gastrectomy.