Work

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

Year: 2025
Type: article
Abstract: 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. In vitro and in vivo 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. This schematic illustrates the design and function of a fouling-resistant, multifunctional hydrogel developed to prevent post-thyroidectomy adhesions. The zwitterionic SAG hydrogel is applied to the injured thyroid surface, where it resists nonspecific protein adsorption and delivers gallic acid to scavenge reactive oxygen species (ROS). This, in turn, promotes the polarization of macrophages from the pro-inflammatory M1 phenotype to the anti-inflammatory M2 phenotype, downregulates IL-6 and TGF-β1 expression, and inhibits extracellular matrix (ECM) deposition and fibroblast activation. • An antiadhesion barrier is engineered to match the unique anatomical constraints of thyroid surgery. • Gallic-acid antioxidant therapy with SBMA zwitterionic anti-fouling is integrated in a single hydrogel platform. • A comprehensive in-vitro and in-vivo evidence was provided to prove the anti-adhesion efficacy in a thyroid-specific model.
Authors: Ye Zhu, Mingbo Zhang, Luyao Feng, Yurong Chen, Yiming Ren, Yiyang Zhao, Xiaoyu Wu, Xiaomeng Zou, Ao Zhang, Bin Zhu, Yazhong Bu, Qiuyang Li, Yukun Luo
Language: English
Subfield: Surgery
Field: Medicine
Open Access status: gold
Estimated APC paid: $3,400
OpenAlex ID: W7116104753
FWCI: 1.785
Cites: 75
Cited by: 2
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