Chen Guo, Palmer Andre F
Department of Chemical and Biomolecular Engineering, The Ohio State University, Columbus, 43210, USA.
Biotechnol Bioeng. 2009 Apr 15;102(6):1603-12. doi: 10.1002/bit.22200.
A mathematical model was developed to study O(2) transport in a convection enhanced hepatic hollow fiber (HF) bioreactor, with hemoglobin-based O(2) carriers (HBOCs) present in the flowing cell culture media stream of the HF lumen. In this study, four HBOCs were evaluated: PEG-conjugated human hemoglobin (MP4), human hemoglobin (hHb), bovine hemoglobin (BvHb) and polymerized bovine hemoglobin (PolyBvHb). In addition, two types of convective flow in the HF extra capillary space (ECS) were considered in this study. Starling flow naturally occurs when both of the ECS ports are closed. If one of the ECS ports is open, forced convective flow through the ECS will occur due to the imposed pressure difference between the lumen and ECS. This type of flow is referred to as cross-flow in this work, since some of the fluid entering the HF lumen will pass across the HF membrane and exit via the open ECS port. In this work, we can predict the dissolved O(2) concentration profile as well as the O(2) transport flux in an individual HF of the bioreactor by solving the coupled momentum and mass transport equations. Our results show that supplementation of the cell culture media with HBOCs can dramatically enhance O(2) transport to the ECS (containing hepatocytes) and lead to the formation of an in vivo-like O(2) spectrum for the optimal culture of hepatocytes. However, both Starling flow and cross-flow have a very limited effect on O(2) transport in the ECS. Taken together, this work represents a novel predictive tool that can be used to design or analyze HF bioreactors that expose cultured cells to defined overall concentrations and gradients of O(2).
建立了一个数学模型，用于研究对流增强型肝中空纤维（HF）生物反应器中的氧气（O₂）传输，其中基于血红蛋白的氧气载体（HBOCs）存在于HF内腔的流动细胞培养基流中。在本研究中，评估了四种HBOCs：聚乙二醇共轭人血红蛋白（MP4）、人血红蛋白（hHb）、牛血红蛋白（BvHb）和聚合牛血红蛋白（PolyBvHb）。此外，本研究考虑了HF毛细血管外空间（ECS）中的两种对流。当ECS的两个端口都关闭时，自然会发生斯塔林流。如果ECS的一个端口打开，由于内腔和ECS之间施加的压力差，将发生通过ECS的强制对流。在这项工作中，这种类型的流动被称为错流，因为一些进入HF内腔的流体将穿过HF膜并通过开放的ECS端口流出。在这项工作中，我们可以通过求解耦合的动量和质量传输方程来预测生物反应器单个HF中的溶解氧浓度分布以及氧气传输通量。我们的结果表明，在细胞培养基中添加HBOCs可以显著增强氧气向ECS（含肝细胞）的传输，并导致形成类似体内的氧气谱，以实现肝细胞的最佳培养。然而，斯塔林流和错流对ECS中的氧气传输影响都非常有限。综上所述，这项工作代表了一种新型的预测工具，可用于设计或分析将培养细胞暴露于确定的总体浓度和氧气梯度的HF生物反应器。
