Photoactive Poly-L-Lysine gel with resveratrol-magnesium metal polyphenol network: A promising strategy for preventing tracheal anastomotic complications following surgery

Yunxuan Jia; Jingfeng Shi; Bowen Ding; Liang Zhao; Ke Xu; Chuang Hu; Weijiao Xu; Anshun Zhu; Haitang Yang; Xiansong Wang; Feng Yao

doi:10.1016/j.mtbio.2023.100938

Photoactive Poly-L-Lysine gel with resveratrol-magnesium metal polyphenol network: A promising strategy for preventing tracheal anastomotic complications following surgery

Mater Today Bio. 2023 Dec 29:24:100938. doi: 10.1016/j.mtbio.2023.100938. eCollection 2024 Feb.

Authors

Yunxuan Jia¹, Jingfeng Shi², Bowen Ding³, Liang Zhao¹, Ke Xu¹, Chuang Hu⁴, Weijiao Xu¹, Anshun Zhu⁵, Haitang Yang¹, Xiansong Wang⁴, Feng Yao^{1

5}

Affiliations

¹ Department of Thoracic Surgery, Shanghai Chest Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200030, China.
² Department of Respiratory and Critical Care Medicine, No.2 People's Hospital of Fuyang City, Fuyang Infectious Disease Clinical College of Anhui Medical University, Fuyang, 236015, China.
³ Department of Pathology, Shanghai Chest Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200030, China.
⁴ Department of Thoracic Surgery, Shanghai Key Laboratory of Tissue Engineering, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200011, China.
⁵ Wenzhou Medical University, Wenzhou, 325015, China.

Abstract

Postoperative complications at the anastomosis site following tracheal resection are a prevalent and substantial concern. However, most existing solutions primarily focus on managing symptoms, with limited attention given to proactively preventing the underlying pathological processes. To address this challenge, we conducted a drug screening focusing on clinically-relevant polyphenolic compounds, given the growing interest in polyphenolic compounds for their potential role in tissue repair during wound healing. This screening led to the identification of resveratrol as the most promising candidate for mitigating tracheal complications, as it exhibited the most significant efficacy in enhancing the expression of vascular endothelial growth factor (VEGF) while concurrently suppressing the pivotal fibrosis factor: transforming growth factor-beta 1 (TGF-β1), showcasing its robust potential in addressing these issues. Building upon this discovery, we further developed an innovative photosensitive poly-L-lysine gel integrated with a resveratrol-magnesium metal polyphenol network (MPN), named Res-Mg/PL-MA. This design allows for the enables sustained release of resveratrol and synergistically enhances the expression of VEGF and also promotes resistance to tensile forces, aided by magnesium ions, in an anastomotic tracheal fistula animal models. Moreover, the combination of resveratrol and poly-L-lysine hydrogel effectively inhibits bacteria, reduces local expression of key inflammatory factors, and induces polarization of macrophages toward an anti-inflammatory phenotype, as well as inhibits TGF-β1, consequently decreasing collagen production levels in an animal model of post-tracheal resection. In summary, our novel Res-Mg/PL-MA hydrogel, through antibacterial, anti-inflammatory, and pro-vascularization mechanisms, effectively prevents complications at tracheal anastomosis, offering significant promise for translational applications in patients undergoing tracheal surgeries.

Keywords: Anastomotic complications; Hydrogels; Metal-polyphenol networks; Resveratrol; Stenosis; Tracheal resection.