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调节电纺纤维的导电性和内部结构以促进心肌细胞伸长和同步跳动。

Tuning the conductivity and inner structure of electrospun fibers to promote cardiomyocyte elongation and synchronous beating.

作者信息

Liu Yaowen, Lu Jinfu, Xu Guisen, Wei Jiaojun, Zhang Zhibin, Li Xiaohong

机构信息

School of Life Sciences, School of Materials Science and Engineering, Southwest Jiaotong University, Key Laboratory of Advanced Technologies of Materials, Ministry of Education, Chengdu 610031, PR China; College of Food Science, Sichuan Agricultural University, Yaan 625014, PR China.

School of Life Sciences, School of Materials Science and Engineering, Southwest Jiaotong University, Key Laboratory of Advanced Technologies of Materials, Ministry of Education, Chengdu 610031, PR China.

出版信息

Mater Sci Eng C Mater Biol Appl. 2016 Dec 1;69:865-74. doi: 10.1016/j.msec.2016.07.069. Epub 2016 Jul 27.

Abstract

The key to addressing the challenges facing cardiac tissue engineering is the integration of physical, chemical, and electrical cues into scaffolds. Aligned and conductive scaffolds have been fabricated as synthetic microenvironments to improve the function of cardiomyocytes. However, up to now, the influence of conductive capability and inner structure of fibrous scaffolds have not been determined on the cardiomyocyte morphologies and beating patterns. In the current study, highly aligned fibers were fabricated with loaded up to 6% of carbon nanotubes (CNTs) to modulate the electrical conductivity, while blend and coaxial electrospinning were utilized to create a bulk distribution of CNTs in fiber matrices and a spatial embedment in fiber cores, respectively. Conductive networks were formed in the fibrous scaffolds after the inoculation of over 3% CNTs, and the increase in the conductivity could maintain the cell viabilities, induce the cell elongation, enhance the production of sarcomeric α-actinin and troponin I, and promote the synchronous beating of cardiomyocytes. Although the conductivity of blend fibers is slightly higher than that of coaxial fibers with the same CNT loadings, the lower exposures to CNTs resulted in higher cell viability, elongation, extracellular matrix secretion and beating rates for cardiomyocytes on coaxial fibers. Taken altogether, core-sheath fibers with loaded 5% of CNTs in the fiber cores facilitated the cardiomyocyte growth with a production of organized contractile proteins and a pulsation frequency close to that of the atrium. It is suggested that electrospun scaffolds that couple conductivity and fibrous structure considerations may provide optimal stimuli to foster cell morphology and functions for myocardial regeneration or establishment of in vitro cardiomyocyte culture platform for drug screening.

摘要

应对心脏组织工程面临挑战的关键在于将物理、化学和电信号整合到支架中。已制备出排列整齐且具有导电性的支架作为合成微环境,以改善心肌细胞的功能。然而,到目前为止,纤维支架的导电能力和内部结构对心肌细胞形态和搏动模式的影响尚未确定。在当前研究中,制备了负载高达6%碳纳米管(CNT)的高度排列纤维以调节电导率,同时分别利用共混和同轴静电纺丝在纤维基质中形成碳纳米管的整体分布以及在纤维芯中形成空间嵌入。接种超过3%的碳纳米管后,在纤维支架中形成了导电网络,电导率的增加可维持细胞活力、诱导细胞伸长、增强肌节α - 肌动蛋白和肌钙蛋白I的产生,并促进心肌细胞的同步搏动。尽管在相同碳纳米管负载量下,共混纤维的电导率略高于同轴纤维,但较低的碳纳米管暴露量使得同轴纤维上的心肌细胞具有更高的细胞活力、伸长、细胞外基质分泌和搏动率。总体而言,在纤维芯中负载5%碳纳米管的核 - 鞘纤维促进了心肌细胞的生长,产生了有组织的收缩蛋白,且搏动频率接近心房。研究表明,兼顾导电性和纤维结构的电纺支架可能提供最佳刺激,以促进细胞形态和功能,用于心肌再生或建立用于药物筛选的体外心肌细胞培养平台。

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