Injectable gallic acid-engineered zwitterionic hydrogel for preventing postoperative adhesions in thyroid surgery through modulating oxidative stress and inflammation

Postoperative adhesions after thyroid surgery pose significant clinical challenges, leading to dysphagia and reoperation risks. Current anti-adhesion barriers are limited by poor anatomical conformity of membranes, short retention time of gels, and insufficient ability to regulate the microenvironment involved in adhesion formation. To address this issue, an injectable SAG adhesive hydrogel is developed by integrating gallic acid (for oxidation regulation) and a zwitterionic polymer (for anti-fouling), to create a stable barrier that physically separates wounds while modulating the pathological microenvironment. The SAG hydrogel exhibits excellent injectability, biodegradability, and anti-fouling performance. <i>In vitro</i> and <i>in vivo</i> studies confirm it suppresses pro-inflammatory cytokine expression and alleviates oxidative stress. In rat thyroid surgery models, SAG hydrogel reduces tissue fibrosis and prevents adhesion formation through dual mechanisms: 1) providing a stable physical barrier, and 2) modulating the local microenvironment via downregulation of fibrotic markers (COL-1/TGF-β) and inflammatory cytokines (IL-6/TNF-α). Functional recovery tests demonstrate improved restoration of respiratory and swallowing capacities. Transcriptomics further validates its role in inhibition of fibrosis via downregulation of ECM-receptor interaction, focal adhesion, PI3K-AKT pathway, cell adhesion molecules, and TGF-β pathways. This work offers a promising strategy for preventing postoperative thyroid adhesions by combining physical barrier functions with local microenvironment modulation.