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通过生物打印各向异性器官构建块对工程化心脏组织中的细胞排列进行编程。

Programming Cellular Alignment in Engineered Cardiac Tissue via Bioprinting Anisotropic Organ Building Blocks.

机构信息

John A. Paulson School of Engineering and Applied Sciences and Wyss Institute for Biologically Inspired Engineering, Harvard University, Cambridge, MA, 02138, USA.

Wyss Institute for Biologically Inspired Engineering, Harvard University, Cambridge, MA, 02138, USA.

出版信息

Adv Mater. 2022 Jul;34(26):e2200217. doi: 10.1002/adma.202200217. Epub 2022 May 25.

DOI:10.1002/adma.202200217
PMID:35451188
Abstract

The ability to replicate the 3D myocardial architecture found in human hearts is a grand challenge. Here, the fabrication of aligned cardiac tissues via bioprinting anisotropic organ building blocks (aOBBs) composed of human induced pluripotent stem cell derived cardiomyocytes (hiPSC-CMs) is reported. A bioink composed of contractile cardiac aOBBs is first generated and aligned cardiac tissue sheets with linear, spiral, and chevron features are printed. Next, aligned cardiac macrofilaments are printed, whose contractile force and conduction velocity increase over time and exceed the performance of spheroid-based cardiac tissues. Finally, the ability to spatially control the magnitude and direction of contractile force by printing cardiac sheets with different aOBB alignment is highlighted. This research opens new avenues to generating functional cardiac tissue with high cell density and complex cellular alignment.

摘要

复制人类心脏中发现的 3D 心肌结构的能力是一个巨大的挑战。在这里,通过生物打印各向异性器官构建块(aOBB)来制造对齐的心脏组织,这些构建块由人诱导多能干细胞衍生的心肌细胞(hiPSC-CMs)组成。首先生成由收缩性心脏 aOBB 组成的生物墨水,并打印具有线性、螺旋形和人字形特征的对齐心脏组织片。接下来,打印对齐的心脏宏观纤维,其收缩力和传导速度随时间增加,并超过基于球体的心脏组织的性能。最后,通过打印具有不同 aOBB 对齐方式的心脏片来突出显示空间控制收缩力幅度和方向的能力。这项研究为生成具有高细胞密度和复杂细胞对齐的功能性心脏组织开辟了新途径。

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