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Self-adhesion conductive cardiac patch based on methoxytriethylene glycol-functionalized graphene effectively improves cardiac function after myocardial infarction
Journal of Advanced Research ( IF 11.4 ) Pub Date : 2024-11-19 , DOI: 10.1016/j.jare.2024.11.026
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

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.


中文翻译:


基于甲氧基三甘醇功能化石墨烯的自粘性导电心脏贴剂可有效改善心肌梗死后的心脏功能


 介绍


心肌梗死 (MI) 后心脏的异常电活动可能导致心力衰竭或心源性猝死。基于石墨烯的导电水凝胶可以模拟心肌组织的微环境,改善心肌梗死后的心脏功能。然而,现有的石墨烯及其衍生物制备方法存在纯度低、工艺复杂、结构不明确等缺点,限制了其生物学应用。

 目标


我们提出了一种优化的合成路线,用于合成具有明确结构的甲氧基三甘醇功能化石墨烯 (TEG-GR)。本研究的目的是建立一种基于 TEG-GR 的新型自粘性导电心脏贴剂,用于保护 MI 后的心脏功能。

 方法


我们优化了π延伸聚合 (APEX) 反应以合成 TEG-GR。将 TEG-GR 掺入多巴胺修饰的明胶 (GelDA) 中以构建导电心脏贴剂 (TEG-GR/GelDA)。我们在 MI 大鼠模型中验证了 TEG-GR/GelDA 心脏补片的功能,并通过 RNA 测序和分子生物学实验探讨了 TEG-GR/GelDA 心脏补片的作用机制。

 结果


甲氧基三甘醇侧链赋予石墨烯高导电性、低免疫原性和卓越的生物学特性。在大鼠中,与非导电心脏补片相比,将 TEG-GR/GelDA 心脏补片移植到心脏梗死区域可以更有效地提高射血分数、减弱胶原蛋白沉积、缩短 QRS 间期并增加治疗后 28 天的血管密度。转录组分析表明,TEG-GR/GelDA 心脏贴剂可以通过维持间隙连接、促进血管生成和抑制心肌细胞凋亡来改善心脏功能。

 结论


具有明确官能团的聚合物的精确合成扩展了石墨烯在生物医学领域的应用,新型心脏贴剂可以成为治疗心肌梗死的有前途的候选者。
更新日期:2024-11-19
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