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用于增强心肌细胞成熟及心脏药物筛选中细胞间通讯的石墨烯SU-8平台

Graphene SU-8 Platform for Enhanced Cardiomyocyte Maturation and Intercellular Communication in Cardiac Drug Screening.

作者信息

Li Longlong, Shanmugasundaram Arunkumar, Kim Jongyun, Oyunbaatar Nomin-Erdene, Kanade Pooja P, Cha Seong-Eung, Lim Daeyun, Lee Chil-Hyoung, Kim Young-Baek, Lee Bong-Kee, Kim Eung-Sam, Lee Dong-Weon

机构信息

Department of Mechanical Engineering, Chonnam National University, Gwangju 61186, Republic of Korea.

Advanced Medical Device Research Center for Cardiovascular Disease, Chonnam National University, Gwangju 61186, Republic of Korea.

出版信息

ACS Nano. 2024 Dec 10;18(49):33293-33309. doi: 10.1021/acsnano.4c05365. Epub 2024 Nov 26.

Abstract

Cell culture substrates designed for myocardial applications are pivotal in promoting the maturation and functional integration of cardiomyocytes. However, traditional in vitro models often inadequately mimic the diverse biochemical signals and electrophysiological properties of mature cardiomyocytes. Herein, we propose the application of monolayer graphene, transferred onto SU-8 cantilevers integrated with a microelectrode array, to evaluate its influence on the structural, functional, and electro-mechano-physiological properties of cardiomyocytes. The monolayer graphene, prepared using chemical vapor deposition, is adeptly transferred to the target substrates via thermal release tape. The electrical conductivity of these graphene-enhanced SU-8 substrates is about 1600 S/cm, markedly surpassing that of previously reported cell culture substrates. Immunofluorescence staining and Western blot analyses reveal that the electrically conductive graphene significantly enhances cardiomyocyte maturation and cardiac marker expression compared to bare SU-8 substrates. Cardiomyocytes cultured on graphene-transferred substrates exhibit conduction velocity approximately 3.4 times greater than that of the control group. Such improvements in cardiac marker expression, mechano-electrophysiological performance lead to better responsiveness to cardiovascular drugs, such as Verapamil and Isoproterenol. While the graphene monolayer does not fully replicate the complex environment found in native cardiac tissue, its use on SU-8 substrates offers a feasible approach for accelerating cardiomyocyte maturation and facilitating drug screening applications.

摘要

为心肌应用设计的细胞培养基质对于促进心肌细胞的成熟和功能整合至关重要。然而,传统的体外模型往往无法充分模拟成熟心肌细胞的多种生化信号和电生理特性。在此,我们提出将转移到集成有微电极阵列的SU-8悬臂上的单层石墨烯用于评估其对心肌细胞的结构、功能和机电生理特性的影响。使用化学气相沉积制备的单层石墨烯通过热释放胶带巧妙地转移到目标基板上。这些石墨烯增强的SU-8基板的电导率约为1600 S/cm,明显超过先前报道的细胞培养基板。免疫荧光染色和蛋白质印迹分析表明,与裸露的SU-8基板相比,导电石墨烯显著增强了心肌细胞的成熟和心脏标志物表达。在石墨烯转移基板上培养的心肌细胞的传导速度比对照组快约3.4倍。心脏标志物表达、机电生理性能的这种改善导致对心血管药物(如维拉帕米和异丙肾上腺素)的反应更好。虽然石墨烯单层不能完全复制天然心脏组织中的复杂环境,但其在SU-8基板上的应用为加速心肌细胞成熟和促进药物筛选应用提供了一种可行的方法。

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