Self-adhesion conductive cardiac patch based on methoxytriethylene glycol-functionalized graphene effectively improves cardiac function after myocardial infarction

Xu Wang; Hao Wang; Xin Liu; Yuan Zhang; Jiamin Li; Heng Liu; Jing Feng; Wenqian Jiang; Ling Liu; Yongchao Chen; Xiaohan Li; Limin Zhao; Jing Guan; Yong Zhang

doi:10.1016/j.jare.2024.11.026

Self-adhesion conductive cardiac patch based on methoxytriethylene glycol-functionalized graphene effectively improves cardiac function after myocardial infarction

J Adv Res. 2024 Nov 18:S2090-1232(24)00545-9. doi: 10.1016/j.jare.2024.11.026. Online ahead of print.

Authors

Xu Wang¹, Hao Wang², Xin Liu³, Yuan Zhang², Jiamin Li³, Heng Liu¹, Jing Feng¹, Wenqian Jiang¹, Ling Liu¹, Yongchao Chen¹, Xiaohan Li¹, Limin Zhao¹, Jing Guan⁴, Yong Zhang⁵

Affiliations

¹ State Key Laboratory of Frigid Zone Cardiovascular Diseases (SKLFZCD), Department of Pharmacology, College of Pharmacy, and Department of Cardiology, the Second Affiliated Hospital, Harbin Medical University, Harbin 150081, China.
² Department of Organic Chemistry, College of Pharmacy, Harbin Medical University, Harbin 150081, China.
³ State Key Laboratory of Frigid Zone Cardiovascular Diseases (SKLFZCD), Department of Pharmacology, College of Pharmacy, and Department of Cardiology, the Second Affiliated Hospital, Harbin Medical University, Harbin 150081, China; State Key Labratoray -Province Key Laboratories of Biomedicine-Pharmaceutics of China, and Key Laboratory of Cardiovascular Research, Ministry of Education, College of Pharmacy, Harbin 150081, China; Research Unit of Noninfectious Chronic Diseases in Frigid Zone (2019RU070), Chinese Academy of Medical Sciences, Harbin 150081, China.
⁴ Department of Organic Chemistry, College of Pharmacy, Harbin Medical University, Harbin 150081, China. Electronic address: guanjing@ems.hrbmu.edu.cn.
⁵ State Key Laboratory of Frigid Zone Cardiovascular Diseases (SKLFZCD), Department of Pharmacology, College of Pharmacy, and Department of Cardiology, the Second Affiliated Hospital, Harbin Medical University, Harbin 150081, China; State Key Labratoray -Province Key Laboratories of Biomedicine-Pharmaceutics of China, and Key Laboratory of Cardiovascular Research, Ministry of Education, College of Pharmacy, Harbin 150081, China; Research Unit of Noninfectious Chronic Diseases in Frigid Zone (2019RU070), Chinese Academy of Medical Sciences, Harbin 150081, China. Electronic address: hmuzhangyong@hotmail.com.

PMID: 39566818
DOI: 10.1016/j.jare.2024.11.026

Abstract

Introduction: Abnormal electrical activity of the heart following myocardial infarction (MI) may lead to heart failure or sudden cardiac death. Graphene-based conductive hydrogels can simulate the microenvironment of myocardial tissue and improve cardiac function post-MI. However, existing methods for preparing graphene and its derivatives suffer from drawbacks such as low purity, complex processes, and unclear structures, which limiting their biological applications.

Objectives: We propose an optimized synthetic route for synthesizing methoxytriethylene glycol-functionalized graphene (TEG-GR) with a defined structure. The aim of this study was to establish a novel self-adhesion conductive cardiac patch based on TEG-GR for protecting cardiac function after MI.

Methods: We optimized π-extension polymerization (APEX) reaction to synthesize TEG-GR. TEG-GR was incorporated into dopamine-modified gelatin (GelDA) to construct conductive cardiac patch (TEG-GR/GelDA). We validated the function of TEG-GR/GelDA cardiac patch in rat models of MI, and explored the mechanism of TEG-GR/GelDA cardiac patch by RNA sequencing and molecular biology experiments.

Results: Methoxytriethylene glycol side chain endows graphene with high electrical conductivity, low immunogenicity, and superior biological properties. In rats, transplantation of TEG-GR/GelDA cardiac patch onto the infarcted area of heart can more effectively enhance ejection fraction, attenuate collagen deposition, shorten QRS interval and increase vessel density at 28 days post-treatment, compared to non-conductive cardiac patch. Transcriptome analysis indicates that TEG-GR/GelDA cardiac patch can improve cardiac function by maintaining gap junction, promoting angiogenesis, and suppressing cardiomyocytes apoptosis.

Conclusion: The precision synthesis of polymer with defined functional group expands the application of graphene in biomedical field, and the novel cardiac patch can be a promising candidate for treating MI.

Keywords: Cardiac patch; Conductive biomaterials; Gap junction; Graphene; Myocardial infarction.