3D bioprinted functional and contractile cardiac tissue constructs.

3D bioprinted functional and contractile cardiac tissue constructs.
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DOI:
10.1016/j.actbio.2018.02.007
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发表时间:
2018-04-01
期刊:
影响因子:
9.7
通讯作者:
Atala A
Atala A
中科院分区:
工程技术1区
文献类型:
--
作者:
Wang Z;Lee SJ;Cheng HJ;Yoo JJ;Atala A

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由原代心肌细胞组成的功能性心肌组织的生物工程技术在心肌再生和体外组织建模方面具有很大的潜力。然而,它的应用仍然有限,因为心脏组织是一个高度组织的结构,具有独特的生理、生物力学和电学特性。在这项研究中,我们进行了一项概念验证研究,通过使用三维生物打印策略来开发具有细胞组织、均匀性和可扩展性的可收缩心脏组织。从幼鼠心脏中分离原代心肌细胞,悬浮在基于纤维蛋白的生物墨水中,以确定心脏组织工程的打印能力。利用牺牲型水凝胶和支撑型聚合物框架,通过300 μm喷嘴,加压空气依次打印出承载细胞的水凝胶。生物打印的心脏组织结构在培养中具有自发的同步收缩,这意味着心脏组织在体外发育和成熟。α-肌动蛋白和连接蛋白43免疫染色证实心肌组织发育进展,心肌细胞排列均匀、致密、机电偶联。这些结构对已知的心脏药物的搏动频率和收缩力表现出生理反应。此外,Notch信号阻断显著加速了生物打印心脏组织的发育和成熟。我们的结果证明了生物打印功能心脏组织的可行性,可以用于组织工程应用和制药目的。
Bioengineering of a functional cardiac tissue composed of primary cardiomyocytes has great potential for myocardial regeneration and in vitro tissue modeling. However, its applications remain limited because the cardiac tissue is a highly organized structure with unique physiologic, biomechanical, and electrical properties. In this study, we undertook a proof-of-concept study to develop a contractile cardiac tissue with cellular organization, uniformity, and scalability by using three-dimensional (3D) bioprinting strategy. Primary cardiomyocytes were isolated from infant rat hearts and suspended in a fibrin-based bioink to determine the priting capability for cardiac tissue engineering. This cell-laden hydrogel was sequentially printed with a sacrificial hydrogel and a supporting polymeric frame through a 300-μm nozzle by pressured air. Bioprinted cardiac tissue constructs had a spontaneous synchronous contraction in culture, implying in vitro cardiac tissue development and maturation. Progressive cardiac tissue development was confirmed by immunostaining for α-actinin and connexin 43, indicating that cardiac tissues were formed with uniformly aligned, dense, and electromechanically coupled cardiac cells. These constructs exhibited physiologic responses to known cardiac drugs regarding beating frequency and contraction forces. In addition, Notch signaling blockade significantly accelerated development and maturation of bioprinted cardiac tissues. Our results demonstrated the feasibility of bioprinting functional cardiac tissues that could be used for tissue engineering applications and pharmaceutical purposes.
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