Biomimetic interfacial water-regulated hybrid dual-layer hydrogel for wound healing, anti-adhesion and hemostasis post partial hepatectomy

Biomimetic hydrogels, with their excellent biocompatibility and tissue adaptability, have garnered significant attention in the field of wound repair. Dual-layer hydrogels can simultaneously achieve hemostasis and anti-adhesion, demonstrating notable potential for application in liver resection surgery. However, existing systems suffer from insufficient mechanical properties and wet adhesion capabilities, and their efficacy in promoting liver wound healing is limited, severely hindering their clinical translation. To address the complex microenvironment of post-liver resection wounds, this study developed a dual-layer functional hydrogel (DAR@Glu) comprising an anti-adhesion layer (AAL) and a repair layer (RL). Through the synergistic interaction of interfacial water regulation and a multi-hydrogen-bond network, this material combines stable wet adhesion with anti-adhesion properties: the repair layer achieves strong wet adhesion via dynamic covalent bonds and hydrogen bonds, while the introduction of glutamic acid further enhances liver tissue repair activity; the anti-adhesion layer forms a dense hydrated layer that effectively prevents tissue adhesion. In vitro experiments confirmed that DAR@Glu can stably adhere to a 1.5 kg weight underwater, demonstrating excellent mechanical properties and sustained wet adhesion. In a rat partial liver resection model, the introduction of glutamic acid significantly enhanced liver tissue repair efficacy. Postoperative day 7 regional quantitative immunohistochemical analysis of liver tissues showed that in the focal regenerative region at the hydrogel-adjacent liver wound edge, the positive staining levels of Cyclin D1, Ki67 and PCNA in the DAR@Glu group were all significantly increased compared with the control group.The CD68 positivity rate was the lowest, while the hydrogel also demonstrated good hemostatic effects; in a cecal injury model, this hydrogel effectively inhibited intra-abdominal adhesions. Therefore, DAR@Glu can efficiently promote wound healing, hemostasis, and anti-adhesion after liver resection, providing an innovative strategy for the clinical repair of liver injuries.