Avidin-biotin binding-based cell seeding and perfusion culture of liver-derived cells in a porous scaffold with a three-dimensional interconnected flow-channel network

Avidin-biotin binding-based cell seeding and perfusion culture of liver-derived cells in a porous scaffold with a three-dimensional interconnected flow-channel network
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DOI:
10.1016/j.biomaterials.2007.05.004
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发表时间:
2007-09-01
期刊:
影响因子:
14
通讯作者:
Sakai, Yasuyuki
Sakai, Yasuyuki
中科院分区:
工程技术1区
文献类型:
--
作者:
Huang, Hongyun;Oizumi, Shunsuke;Sakai, Yasuyuki

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为了工程化可植入肝组织,我们设计了一种具有三维分支和连接流动通道网络的新型支架,该网络包括多个四面体单元(4-mm边长)。对于该网络的制造,将可生物降解的聚己内酯(PCL)和80%(w/w)的NaCl盐颗粒作为致孔剂充分混合,并应用于选择性激光烧结(SLS)工艺,一种适用于快速成型的技术。因此,我们获得了具有100-200 μ m孔径和3D流动通道的高(89%)孔隙率的支架。为了评价其生物相容性,使用亲和素-生物素(AB)结合将人肝癌Hep G2细胞接种到支架中,并在灌注系统中培养9天。结果表明,这种三维流动通道对细胞的生长和功能至关重要。此外,基于AB结合的接种显著改善了细胞负载支架的整体性能。基于相同的设计和使用人类肝细胞祖细胞,制造一个更精细的支架,具有500 cm(3)的规模,可能会在不久的将来导致用于人类的可植入肝组织等效物的开发。(c)2007爱思唯尔有限公司保留所有权利。
To engineer implantable liver tissues, we designed a novel scaffold with a three-dimensional (31)) branching and joining flow-channel network comprising multiple tetrahedral units (4-mm edge length). For the fabrication of this network, biodegradable polycaprolactone (PCL) and 80% (w/w) NaCl salt particles serving as porogen were thoroughly mixed and applied in a selective laser sintering (SLS) process, a technique adapted to rapid prototyping. We thus obtained a scaffold that had high (89%) porosity with a pore size of 100-200 mu m and 3D flow channels. To evaluate its biocompatibility, human hepatoma Hep G2 cells were seeded into the scaffold using avidin-biotin (AB) binding and cultured in a perfusion system for 9 days. The results demonstrated that such 3D flow channels are essential to the cells' growth and function. In addition, the AB binding-based seeding remarkably improved the overall performance of the cell-loaded scaffolds. The fabrication of a much finer scaffold, having a 500cm(3) scale, based on the same design and the use of human hepatocyte progenitors, may, in the near future, lead to the development of an implantable liver tissue equivalent for use in humans. (c) 2007 Elsevier Ltd. All rights reserved.