Zwitterionic polymer nanocomposite hydrogels with immunoregulation for effectively preventing postoperative abdominal adhesions.

Abstract

Zwitterionic hydrogels are attractive physical barriers for preventing postoperative abdominal adhesions because of their outstanding antifouling properties; however, their inherent biological inertness and poor degradability often hinder therapeutic efficacy and clinical translational potential. Herein, we report a bioactive and dissociable zwitterionic nanocomposite hydrogel that integrates zwitterionic polymer chains with clearance potential, hydrolytically dissociable networks, and Prussian blue (PB) nanozymes. A molecular-weight-controlled polycarboxybetaine acrylate precursor (PCBOAA, ∼50 kDa) was prepared by reversible addition-fragmentation chain-transfer (RAFT) polymerization and subsequently crosslinked with dithiothreitol via thiol-acrylate Michael addition reaction to form a zwitterionic hydrogel featuring β-thioether ester linkage, which could gradually dissociate under physiological conditions into low-molecular-weight polymer with reduced risk of prolonged retention. Incorporation of PB nanoparticles further endowed the PCBOAA@PB hydrogel with antioxidative and immunomodulatory activity. In vitro, PCBOAA@PB hydrogel could effectively resist protein adsorption and cell adhesion and suppress pro-inflammatory macrophage polarization. In a rat cecum-abdominal wall adhesion model, it exhibited markedly superior anti-adhesion efficacy compared with a clinically used hyaluronic acid hydrogel. Mechanistically, this excellent anti-adhesion efficacy of PCBOAA@PB hydrogel as a physical barrier stemmed from its dual ability to reprogram the postoperative inflammatory-fibrotic microenvironment and reduce excessive collagen deposition. In summary, this work provides a zwitterionic hydrogel design strategy that integrates antifouling, microenvironment modulation, and clearance potential for effective adhesion prevention.