Optimizing normoxic conditions in liver devices using enhanced gel matrices.
Optimizing normoxic conditions in liver devices using enhanced gel matrices.
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使用增强型凝胶基质优化肝脏装置中的含氧量正常条件。
DOI：
10.1002/bit.21681
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发表时间：
2008
影响因子：
3.8
通讯作者：
Coger,RobinN
中科院分区：
文献类型：
--
作者：
Niu,Mei;Clemens,MarkG;Coger,RobinN
对于体外肝脏替代装置，例如填充床生物反应器，为了维持肝脏的基本功能，它们必须至少成功地支持肝细胞，即肝脏的实质细胞。在体内，肝脏是氧气的主要消耗者。因此，氧气（O2）的有限运输距离决定了工程化装置的细胞空间的尺寸，这并不奇怪。由于细胞空间容量直接影响装置的性能，因此O2运输是生物反应器设计规模扩大的关键问题。在目前的调查中，细胞外基质（ECM）的微孔性已被修改，以进一步改善O2运输填充床设备超出以前在文献中报道。对O2增强技术的这些改进使O2转运距离在无细胞条件下达到481.7 ± 12.5 µm;在存在100万个肝细胞的情况下达到418.1 ± 6.0 µm。两个值均显著大于106个肝细胞包装在正常非增强ECM凝胶中时获得的170 µm基线值。这项研究的结果还表明，氧增强技术具有防止严重缺氧和高氧区域在细胞空间内发展的额外好处。因此，增强的ECM凝胶使堆积的肝细胞能够保持比正常非增强凝胶更好的肝细胞代谢状态。Biotechnol. Bioeng. 2008;99：1502-1512。© 2007 Wiley Periodicals，Inc.
For in vitro liver replacement devices, such as packed bed bioreactors, to maintain the essential functions of the liver, they must at least successfully support hepatocytes, the parenchymal cell of the liver. In vivo, the liver is a major consumer of oxygen. Hence it is unsurprising that the limited transport distance of oxygen (O2) governs the dimensions of the cellular space of engineered devices. Because cellular space capacity directly affects the device's performance, O2transport is a critical issue in the scale up of bioreactor designs. In the current investigation, the microporosity of the extracellular matrix (ECM) has been modified to further improve O2transport in packed bed devices beyond that previously reported in the literature. These improvements to the O2enhancement technique enabled O2transport distances of 481.7 ± 12.5 µm to be achieved under acellular conditions; and distances of 418.1 ± 6.0 µm to be attained in the presence of 1 million hepatocytes. Both values are significantly greater than the 170 µm baseline attained when 106hepatocytes are packed within normal non‐enhanced ECM gels. The study's results also illustrate that the O2enhancement technique has the added benefit of preventing regions of severe hypoxia and hyperoxia from developing within the cellular space. As such, enhanced ECM gels enable packed hepatocytes to maintain better hepatocellular metabolic status than is possible with normal non‐enhanced gels. Biotechnol. Bioeng. 2008;99: 1502–1512. © 2007 Wiley Periodicals, Inc.