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, Yuan Zhang, Jiamin Li, Heng Liu, Jing Feng, Wenqian Jiang, Ling Liu, Yongchao Chen, Xiaohan Li, Limin Zhao, Jing Guan, Yong Zhang, Yong Zhang
Abstract
Schematic illustration of the formation of an adhesion conductive hydrogel and its application in treating MI rats. ‘TEG-GR’ represents methoxytriethylene glycol-functionalized graphene and ‘GelDA’ represents dopamine-modified gelatin. • Methoxytriethylene glycol-functionalized graphene (TEG-GR) with defined structure was synthesized for the first time. • TEG-GR/GelDA cardiac patch has suitable conductivity and degradation rate for treating MI. • TEG-GR/GelDA cardiac patch enhances myocardial electrical coupling and protects cardiac function. • TEG-GR/GelDA cardiac patch can promote angiogenesis and inhibit cardiomyocytes apoptosis. 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. We propose an optimized synthetic route for synthesizing methoxytriethylene glycol-functionalized graphene (TEG-GR) with a defined structure. The aim of this study is to establish a novel self-adhesion conductive cardiac patch based on TEG-GR for protecting cardiac function after MI. 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. Methoxytriethylene glycol side chain endowed graphene with low immunogenicity and superior biological properties without compromising conductivity. In rats, transplantation of TEG-GR/GelDA cardiac patch onto the infarcted area of heart could 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 indicated that TEG-GR/GelDA cardiac patch could improve cardiac function by maintaining gap junction, promoting angiogenesis, and suppressing cardiomyocytes apoptosis. 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.