Department of Chemical Engineering and Institute of Biomedical Engineering, National Tsing Hua University, Hsinchu 30013, Taiwan, ROC.
Biomaterials. 2013 Jan;34(4):1063-72. doi: 10.1016/j.biomaterials.2012.10.065. Epub 2012 Nov 17.
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.
心肌梗死常伴有电功能异常,这是由于大量功能失调的心肌细胞丧失所致。本工作开发了一种由聚苯胺(PANI)和聚乳酸-共-羟基乙酸(PLGA)的取向复合纳米纤维组成的网格,作为一种电活性支架,可协调培养的心肌细胞同步搏动。HCl 掺杂后,电纺纤维可转化为带正电荷的导电形式,从而吸引带负电荷的黏附蛋白(如纤连蛋白和层粘连蛋白)并增强细胞黏附性。孵育过程中,黏附的心肌细胞彼此关联并形成孤立的细胞簇;每个簇中的细胞伸长并沿纤维网的主轴排列其形态。培养后,在孤立的细胞簇中可以清楚地观察到细胞间连接蛋白 connexin 43 的表达。每个簇中的所有心肌细胞都同步搏动,这表明细胞之间的偶联已完全形成。此外,通过设计电刺激可以同步这些孤立细胞簇的搏动频率,该电刺激旨在模拟天然心脏中的电刺激。重要的是,改善受损的心脏功能取决于植入细胞与宿主心肌之间的电偶联,以确保它们的同步搏动。