Plasma-activated hydrogel promotes postoperative colonic anastomotic leak healing

Xiaoyuan Deng; Kaijie Ren; Tianhao Min; Yuyi Ma; Yuanchang Peng; Siyi Wang; Bo Zhang; Xin Xie; Yanglong Nan; Shiyao Tong; Yuanyuan Liu; Yong Zhang; Kang Li; Wei Wang; Nan Hao; Guanjun Zhang; Chengxue Dang; Tuanhe Sun; Kun Zhu; Hao Zhang

doi:10.1016/j.jare.2026.02.056

Plasma-activated hydrogel promotes postoperative colonic anastomotic leak healing

J Adv Res. 2026 Mar 6:S2090-1232(26)00189-X. doi: 10.1016/j.jare.2026.02.056. Online ahead of print.

Authors

Xiaoyuan Deng¹, Kaijie Ren¹, Tianhao Min¹, Yuyi Ma¹, Yuanchang Peng¹, Siyi Wang¹, Bo Zhang², Xin Xie³, Yanglong Nan¹, Shiyao Tong¹, Yuanyuan Liu¹, Yong Zhang¹, Kang Li¹, Wei Wang⁴, Nan Hao¹, Guanjun Zhang⁵, Chengxue Dang¹, Tuanhe Sun⁶, Kun Zhu⁷, Hao Zhang⁸

Affiliations

¹ Department of Surgical Oncology, The First Affiliated Hospital of Xi' an Jiaotong University, Xi'an, Shaanxi 710061, China.
² Department of Surgical Oncology, The First Affiliated Hospital of Xi' an Jiaotong University, Xi'an, Shaanxi 710061, China; State Key Laboratory of Electrical Insulation and Power Equipment, School of Electrical Engineering, Xi'an Jiaotong University, Xi'an, Shaanxi 710049, China.
³ Department of Nuclear Medicine, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, China.
⁴ Department of Obstetrics and Gynecology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, China.
⁵ State Key Laboratory of Electrical Insulation and Power Equipment, School of Electrical Engineering, Xi'an Jiaotong University, Xi'an, Shaanxi 710049, China.
⁶ Department of Surgical Oncology, The First Affiliated Hospital of Xi' an Jiaotong University, Xi'an, Shaanxi 710061, China; State Key Laboratory of Electrical Insulation and Power Equipment, School of Electrical Engineering, Xi'an Jiaotong University, Xi'an, Shaanxi 710049, China. Electronic address: suntuanhe@xjtu.edu.cn.
⁷ Department of Surgical Oncology, The First Affiliated Hospital of Xi' an Jiaotong University, Xi'an, Shaanxi 710061, China. Electronic address: dr.zhkun@mail.xjtu.edu.cn.
⁸ Department of Surgical Oncology, The First Affiliated Hospital of Xi' an Jiaotong University, Xi'an, Shaanxi 710061, China. Electronic address: hao.zhang@xjtu.edu.cn.

PMID: 41794222
DOI: 10.1016/j.jare.2026.02.056

Abstract

Introduction: Colonic anastomotic leak (CAL) represents one of the most critical complications following gastrointestinal surgery, inducing severe intra-abdominal infections, adhesion formation and persistently high mortality rates. This complication imposes a substantial socioeconomic and healthcare burden.

Objectives: To address this challenge, cold atmospheric plasma (CAP)-loaded hydrogel was developed for intraperitoneal delivery of reactive species to anastomotic sites.

Methods: An anastomotic leak (AL) model was established in SD rats via surgical intervention. For in vitro studies, apoptosis was induced in HCT116 cells by treatment with TNF-α. Apoptosis was assessed using flow cytometry and Western blotting. Inflammatory cytokine levels were measured by enzyme-linked immunosorbent assay (ELISA). Histological changes were evaluated via immunofluorescence staining and immunohistochemistry.

Results: The cold atmospheric plasma-activated hydrogel (Hyd@CAP) gradually formed effective coverage over the anastomotic sites, enabling sustained release reactive oxygen and nitrogen species (RONS). These reactive species collectively exerted multifunctional effects including antimicrobial, anti-inflammatory and tissue-reparative activities. Our research demonstrated consistent adhesive stability at anastomotic sites and significant reduction in adhesion scores. Transcriptomic analysis of anastomotic tissues revealed that Hyd@CAP accelerated regeneration and proliferation of intestinal epithelial cells by releasing RONS that further activated the mTOR signaling pathway, thereby exerting antimicrobial, anti-inflammatory and tissue-reparative effects.

Conclusion: Hyd@CAP represents an emerging therapeutic strategy with potential applications in the management of AL following gastrointestinal surgery. Its efficacy has been preliminarily validated in a rat model of CAL, suggesting potential for early-phase clinical translation and possible extension to anastomotic repair throughout the entire gastrointestinal tract.

Keywords: Colonic anastomotic leak (CAL); Plasma-activated hydrogel (Hyd@CAP); Reactive oxygen and nitrogen species (RONS); Tissue repair; mTOR.