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

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.