A Zwitterionic Hydrogel with Anti‐Oxidative and Anti‐Inflammatory Properties for the Prevention of Peritoneal Adhesion by Inhibiting Mesothelial‐Mesenchymal Transition

Postoperative peritoneal adhesion is a serious clinical complication. Various hydrogel barriers have been developed to prevent peritoneal adhesion. However, it remains a challenge to design a hydrogel with desirable physicochemical properties and bioactivities. In this study, a zwitterionic polysaccharide-based multifunctional hydrogel is developed using epigallocatechin-3-gallate (EGCG) to prevent postoperative abdominal adhesion. This hydrogel is simple to use and has desirable properties, such as excellent injectability, self-healing, and non-swelling properties. The hydrogel also has ultralow fouling capabilities, such as superior bactericidal performance, cell and protein adhesion, and low immunogenicity resistance. Moreover, the hydrogel exhibits good antioxidant activity, which is attributed to the integration of EGCG. Furthermore, the detailed mechanism from in vivo and in vitro experimental studies illustrates that hydrogel compositions can synergistically prevent adhesion formation through multiple pathways, including anti-inflammatory and antioxidant capabilities and inhibition effects on the mesothelial-mesenchymal transition (MMT) process induced by transforming growth factor (TGF-β). In summary, this zwitterionic multifunctional hydrogel has great potential to prevent postoperative adhesion formation in the clinical setting.