Functional assembly of engineered myocardium by electrical stimulation of cardiac myocytes cultured on scaffolds
Functional assembly of engineered myocardium by electrical stimulation of cardiac myocytes cultured on scaffolds
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DOI：
10.1073/pnas.0407817101
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发表时间：
2004-12-28
影响因子：
11.1
通讯作者：
Vunjak-Novakovic, G
中科院分区：
文献类型：
--
作者：
Radisic, M;Park, H;Vunjak-Novakovic, G
组织工程的主要挑战是指导细胞建立不同层次尺度上被替换组织的生理结构和功能。为了工程化心肌，细胞的生物物理调节需要重现天然心脏中存在的多种信号。我们假设兴奋-收缩偶联对正常心脏的发育和功能至关重要，决定了工程心肌的发育和功能。为了诱导培养的心脏结构的同步收缩，我们施加了旨在模拟天然心脏的电信号。在体外仅8天，电场刺激诱导细胞排列和耦合，同步构建收缩的幅度增加了7倍，并导致了显着水平的超微结构组织。心脏结构的传导性和收缩性的发展是同步的，强烈依赖于电刺激的开始和持续时间。
The major challenge of tissue engineering is directing the cells to establish the physiological structure and function of the tissue being replaced across different hierarchical scales. To engineer myocardium, biophysical regulation of the cells needs to recapitulate multiple signals present in the native heart. We hypothesized that excitation-contraction coupling, critical for the development and function of a normal heart, determines the development and function of engineered myocardium. To induce synchronous contractions of cultured cardiac constructs, we applied electrical signals designed to mimic those in the native heart. Over only 8 days in vitro, electrical field stimulation induced cell alignment and coupling, increased the amplitude of synchronous construct contractions by a factor of 7, and resulted in a remarkable level of ultrastructural organization. Development of conductive and contractile properties of cardiac constructs was concurrent, with strong dependence on the initiation and duration of electrical stimulation.