Abstract

Gastrointestinal wall defects (e.g., perforations and leaks) present significant clinical challenges due to high rates of leakage, infection, and postoperative tissue adhesions. Current synthetic patches lack biocompatibility, leading to chronic inflammation, poor tissue integration, and postoperative tissue adhesion. To overcome these issues, this study introduces a multifunctional tissue-engineered gastrointestinal patch (TEGIP) that combines an extracellular matrix (ECM)-derived biomaterials with a wet-adhesive system and an anti-adhesion layer. The tri-layer TEGIP, designed for rapid modular assembly using off-the-shelf components, comprises an acellular dermal matrix (ADM) for mechanical support and tissue repair; a photo-crosslinkable methacrylated hyaluronic acid (HAMA) hydrogel layer to minimize peritoneal attachments; and a polyethyleneimine/polyacrylic acid (PEI/PAA) powder-based adhesive for rapid wet bonding. The structural integrity of tri-layer TEGIP is maintained through physical interlocking and interfacial interpenetration without the need for additional chemical crosslinking. In vitro evaluations confirmed robust mechanical durability (11.6 ± 2.0 MPa), effective reduction of cell adhesion by the HAMA layer, and PEI/PAA bonding strength comparable to fibrin glue, and high burst pressures (155 ± 22 mmHg) when sealing a 10-mm perforation. In a rat acute gastric perforation model, the TEGIP effectively sealed defects and significantly reduced postoperative adhesions. Moreover, TEGIP potentially facilitated tissue repair by guiding M2 macrophage polarization and mitigating excessive collagen deposition at repair stie. Additionally, no adverse hepato-renal toxicity was observed, ensuring sustained biocompatibility. These findings position the TEGIP as a promising sutureless solution for gastrointestinal defect sealing, offering robust sealing, enhanced biocompatibility, and reduced adhesion-related complications. Statement of Significance Tri-layered