An Injectable Zwitterionic Hydrogels with Multiple Intermolecular Interactions for Effective Prevention of Abdominal Adhesions

Abstract Postoperative abdominal adhesions are the most common complication following abdominopelvic surgery, posing a significant burden on patients, clinicians, and society. However, current physical barriers often involve a tradeoff between preventing these adhesions and inhibiting inflammation. Herein, a one‐stone‐two‐birds strategy is presented to address this challenge through an injectable intertwined hydrogel containing sulfobetaine, modified aminocaproic acid (A6ACA), and ZnO nanoparticles (PSA‐ZnO hydrogel). This intertwined network is stabilized by multiple intermolecular coordination bonds, including hydrogen bonds and electrostatic interactions—enabling facile injection and resistance to abdominal creep stress. Experimental results demonstrate that PSA‐ZnO hydrogel fully reduce the severity of peritoneal adhesions in treated rats at both 7‐ and 14‐days post‐surgery, outperforming commercially available hyaluronic acid (HA) gel due to its superior antifouling, antibacterial (> 95% clearance of E. coli and S. aureus ,), hemostatic (55 s), and wound healing properties (IL‐6 and TNF‐α decreased and VEGF increased). Unlike conventional barriers, PSA‐ZnO prevents foreign body formation by inhibiting blood clot organization and pathologic fibrin accumulation at wound sites. This integrated approach offers a clinically translatable solution for complete prevention of postoperative adhesions and inflammation, with the potential to improve patient outcomes and reduce healthcare burdens.