Development of a Novel Synthetic Hydrogel Sealant for Effective Prevention of Liver Resection-Associated Bile Leakage

Bile leakage is a major complication following hepatectomy; these often lead to surgical site infections, liver failure, and even death. Biomaterials, including fibrinogen-based collagen fleece (TachoSil) and fibrin glue, are ineffective for bile sealing. Synthetic sealants, including cyanoacrylate and polymer-based materials, independent of coagulation, are inadequate for bile leakage management. Therefore, in the present study, a novel hydrogel-based sealant (DCSN_100_25) is developed using 3 types of poly(ethylene glycol) (PEG) with a dual-stage cross-linking mechanism, termed the delayed cross-linked single network (DCSN). This design facilitates rapid initial solidification followed by gradual network formation, ensuring immediate sealing and stable adhesion to the amputated liver tissue surface. Experiments using in vivo rat hepatectomy models demonstrated that DCSN_100_25 achieved hemostasis within 1 min, outperforming conventional sealants, such as SURGICEL and TachoSil, and effectively preventing both bleeding and bile leakage. Furthermore, in vivo safety assessments confirmed its safety profile, with PEG brushes remaining on the liver tissue and exhibiting minimal inflammation and no chronic liver damage. These findings suggest that DCSN_100_25 is a promising surgical sealant that effectively manages bile leakage and enhances hepatectomy safety.