Mixtures of Hemoglobin-Based Oxygen Carriers and Perfluorocarbons Exhibit a Synergistic Effect in Oxygenating Hepatic Hollow Fiber Bioreactors
Mixtures of Hemoglobin-Based Oxygen Carriers and Perfluorocarbons Exhibit a Synergistic Effect in Oxygenating Hepatic Hollow Fiber Bioreactors
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DOI：
10.1002/bit.22571
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发表时间：
2010-02-15
影响因子：
3.8
通讯作者：
Palmer, Andre F.
中科院分区：
文献类型：
--
作者：
Chen, Guo;Palmer, Andre F.
肝中空纤维（HF）生物反应器正在开发中，用作生物人工肝辅助装置（BLAD）。一般来说，BLAD受到O-2限制的运输，这降低了它们的性能。本建模研究旨在研究由血红蛋白氧载体（HBOCs）和全氟化碳（PFCs）的混合物组成的O-2携带溶液是否可以增强O-2向HF生物反应器毛细血管外空间（ECS）中培养的肝细胞的转运。我们模拟用含有这两种类型的氧载体（HBOCs和PFC）的混合物补充HF生物反应器的循环细胞培养基流。根据商业HF生物反应器的尺寸和物理特性建立了数学模型。所得到的一组偏微分方程，它描述了流体传输，以及，质量传输的溶解O-2在伪均相PFC/水相和含氧HBOC，被解决，以产生O-2浓度场在三个HT域（内腔，膜和ECS）。我们的研究结果表明，HBOC和PFC的混合物显示出协同效应，在氧合ECS，因此，在循环细胞培养基中的HBOC和PFC的存在下，显着提高O-2的运输培养的肝细胞。此外，通过在入口pO（2）为80 mmHg时向HF生物反应器中补充HBOC和PFC的混合物，可以重现肝窦中的体内O-2谱。因此，我们预计PFC基氧载体在较高的O-2水平下（例如，在入口pO（2）为760 mmHg时，其对应于在1 atm下与含水细胞培养基平衡的纯O-2）。Biotechnol. Bioeng. 2010;105：534-542. (C)2009 Wiley Periodicals，Inc.
Hepatic hollow fiber (HF) bioreactors are being developed for use as bioartificial liver assist devices (BLADs). In general, BLADs suffer from O-2 limited transport, which reduces their performance. This modeling study seeks to investigate if O-2 carrying solutions consisting of mixtures of hemoglobin-based oxygen carriers (HBOCs) and perfluorocarbons (PFCs) can enhance O-2 transport to hepatocytes cultured in the extra capillary space (ECS) of HF bioreactors. We simulated supplementing the circulating cell culture media stream of the HF bioreactor with a mixture containing these two types of oxygen carriers (HBOCs and PFCs). A mathematical model was developed based on the dimensions and physical characteristics of a commercial HF bioreactor. The resulting set of partial differential equations, which describes fluid transport; as well as, mass transport of dissolved O-2 in the pseudo-homogeneous PFC/water phase and oxygenated HBOC, was solved to yield the O-2 concentration field in the three HT domains (lumen, membrane and ECS). Our results show that mixtures of HBOC and PFC display a synergistic effect in oxygenating the ECS, Therefore, the presence of both HBOC and PFC in the circulating cell culture media dramatically improves transport Of O-2 to cultured hepatocytes. Moreover, the in vivo O-2 spectrum in a liver sinusoid can be recapitulated by supplementing the HF bioreactor with a Mixture of HBOCs and PFCs at an inlet pO(2) of 80 mmHg. Therefore, we expect that PFC-based oxygen carriers will be more efficient at transporting O-2 at higher O-2 levels (e.g., at an inlet pO(2) of 760 mmHg, which corresponds to Pure O-2 in equilibrium with aqueous cell Culture media at 1 atm). Biotechnol. Bioeng. 2010;105: 534-542. (C) 2009 Wiley Periodicals, Inc.