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柔性纳米薄膜涂覆有取向排列的压电微纤维,可保持心肌细胞的收缩性。

Flexible nanofilms coated with aligned piezoelectric microfibers preserve the contractility of cardiomyocytes.

机构信息

CNC-Center of Neurosciences and Cell Biology, University of Coimbra, 3004-517 Coimbra, Portugal; Instituto de Investigação Interdisciplinar, University of Coimbra, Casa Costa Alemão - Pólo II, Rua Dom Francisco de Lemos, 3030-789 Coimbra, Portugal.

CNC-Center of Neurosciences and Cell Biology, University of Coimbra, 3004-517 Coimbra, Portugal.

出版信息

Biomaterials. 2017 Sep;139:213-228. doi: 10.1016/j.biomaterials.2017.05.048. Epub 2017 May 31.

Abstract

The use of engineered cardiac tissue for high-throughput drug screening/toxicology assessment remains largely unexplored. Here we propose a scaffold that mimics aspects of cardiac extracellular matrix while preserving the contractility of cardiomyocytes. The scaffold is based on a poly(caprolactone) (PCL) nanofilm with magnetic properties (MNF, standing for magnetic nanofilm) coated with a layer of piezoelectric (PIEZO) microfibers of poly(vinylidene fluoride-trifluoroethylene) (MNF+PIEZO). The nanofilm creates a flexible support for cell contraction and the aligned PIEZO microfibers deposited on top of the nanofilm creates conditions for cell alignment and electrical stimulation of the seeded cells. Our results indicate that MNF+PIEZO scaffold promotes rat and human cardiac cell attachment and alignment, maintains the ratio of cell populations overtime, promotes cell-cell communication and metabolic maturation, and preserves cardiomyocyte (CM) contractility for at least 12 days. The engineered cardiac construct showed high toxicity against doxorubicin, a cardiotoxic molecule, and responded to compounds that modulate CM contraction such as epinephrine, propranolol and heptanol.

摘要

用于高通量药物筛选/毒理学评估的工程心脏组织在很大程度上仍未得到探索。在这里,我们提出了一种支架,该支架模拟了心脏细胞外基质的某些方面,同时保持了心肌细胞的收缩性。该支架基于具有磁性的聚己内酯(PCL)纳米薄膜(MNF,代表磁性纳米薄膜),其表面涂有一层聚偏二氟乙烯-三氟乙烯(PIEZO)的微纤维(MNF+PIEZO)。纳米薄膜为细胞收缩提供了一个灵活的支撑,而沉积在纳米薄膜顶部的定向 PIEZO 微纤维则为细胞排列和接种细胞的电刺激创造了条件。我们的结果表明,MNF+PIEZO 支架促进了大鼠和人心肌细胞的附着和排列,保持了细胞群体的比例随时间的变化,促进了细胞间的通讯和代谢成熟,并至少保持了 12 天的心肌细胞(CM)收缩性。该工程心脏结构对多柔比星(一种心脏毒性分子)表现出高毒性,并对调节 CM 收缩的化合物(如肾上腺素、普萘洛尔和庚醇)产生反应。

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