Electrical coupling of isolated cardiomyocyte clusters grown on aligned conductive nanofibrous meshes for their synchronized beating

Electrical coupling of isolated cardiomyocyte clusters grown on aligned conductive nanofibrous meshes for their synchronized beating
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DOI:
10.1016/j.biomaterials.2012.10.065
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发表时间:
2013-01-01
期刊:
影响因子:
14
通讯作者:
Sung, Hsing-Wen
Sung, Hsing-Wen
中科院分区:
工程技术1区
文献类型:
--
作者:
Hsiao, Chun-Wen;Bai, Meng-Yi;Sung, Hsing-Wen

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心肌梗死通常与由于功能性心肌细胞的大量丧失而导致的电功能异常相关。这项工作开发了一个网格,由聚苯胺(PANI)和聚(乳酸-羟基乙酸)(PLGA)的对齐复合纳米纤维组成,作为一个电活性支架,用于协调培养的心肌细胞的跳动同步。在通过HCl掺杂之后,电纺纤维可以转化为携带正电荷的导电形式,其然后可以吸引带负电荷的粘附蛋白(即纤连蛋白和层粘连蛋白)并增强细胞粘附。在孵育期间,粘附的心肌细胞彼此结合并形成孤立的细胞簇;每个簇内的细胞伸长并沿纤维网的主轴沿着其形态。培养后,间隙连接蛋白连接蛋白43的表达清楚地观察到在孤立的集群细胞间。每个簇内的所有心肌细胞都同步跳动,这意味着细胞之间的耦合已经完全发展。此外,这些分离的细胞簇之间的跳动速率可以通过设计成模仿天然心脏中产生的电刺激来同步。重要的是,改善受损的心脏功能取决于移植细胞和宿主心肌之间的电耦合,以确保它们的同步跳动。(C)2012爱思唯尔有限公司保留所有权利。
Myocardial infarction is often associated with abnormalities in electrical function due to a massive loss of functioning cardiomyocytes. This work develops a mesh, consisting of aligned composite nanofibers of polyaniline (PANI) and poly(lactic-co-glycolic acid) (PLGA), as an electrically active scaffold for coordinating the beatings of the cultured cardiomyocytes synchronously. Following doping by HCl, the electrospun fibers could be transformed into a conductive form carrying positive charges, which could then attract negatively charged adhesive proteins (i.e. fibronectin and laminin) and enhance cell adhesion. During incubation, the adhered cardiomyocytes became associated with each other and formed isolated cell clusters; the cells within each cluster elongated and aligned their morphology along the major axis of the fibrous mesh. After culture, expression of the gap-junction protein connexin 43 was clearly observed intercellularly in isolated clusters. All of the cardiomyocytes within each cluster beat synchronously, implying that the coupling between the cells was fully developed. Additionally, the beating rates among these isolated cell clusters could be synchronized via an electrical stimulation designed to imitate that generated in a native heart. Importantly, improving the impaired heart function depends on electrical coupling between the engrafted cells and the host myocardium to ensure their synchronized beating. (C) 2012 Elsevier Ltd. All rights reserved.