Bioengineering of High Cell Density Tissues with Hierarchical Vascular Networks for Ex Vivo Whole Organs

Bioengineering of High Cell Density Tissues with Hierarchical Vascular Networks for Ex Vivo Whole Organs
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用于离体整个器官的具有分层血管网络的高细胞密度组织的生物工程

DOI:
10.1002/adma.202209149
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发表时间:
2023
期刊:
影响因子:
29.4
通讯作者:
Mabuchi Mamoru
Mabuchi Mamoru
中科院分区:
材料科学1区
文献类型:
--
作者:
Wu Peizheng;Asada Hiroki;Hakamada Masataka;Mabuchi Mamoru

文献摘要

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组织样结构如细胞片、球状体和类器官的发展有助于再生医学的进步。同时实现这些组织的放大和高细胞密度是具有挑战性的,因为不能向大的高细胞密度组织的内部供应足够的氧气。在此,显示了在体外制造血管以向毫米大小的无支架组织内部供应氧气,该组织的细胞密度为2.2亿个细胞mL-1,对应于天然组织的细胞密度。由毛细血管和大血管的吻合形成的分级血管网络对于氧气供应是必不可少的,而大血管或毛细血管网络单独对供应的贡献可以忽略不计。分层血管网络是通过自上而下的方法形成的,这为离体整个器官提供了一种新的选择,而无需脱细胞和3D生物打印。
The development of tissue‐like structures such as cell sheets, spheroids, and organoids has contributed to progress in regenerative medicine. Simultaneous achievement of scale up and high cell density of these tissues is challenging because sufficient oxygen cannot be supplied to the inside of large, high cell density tissues. Here, in vitro fabrication of vessels to supply oxygen to the inside of millimeter‐sized scaffold‐free tissues whose cell density is ≈200 million cells mL−1, corresponding to those of native tissues, is shown. Hierarchical vascular networks by anastomosis of capillaries and a large vessel are essential for oxygen supply, whereas a large vessel or capillary networks alone make negligible contributions to the supply. The hierarchical vascular networks are formed by a top‐down approach, which offers a new option for ex vivo whole organs without decellularization and 3D‐bioprinting.