Effect of flow configuration and membrane characteristics on membrane fouling in a novel multicoaxial hollow-fiber bioartificial liver.
Effect of flow configuration and membrane characteristics on membrane fouling in a novel multicoaxial hollow-fiber bioartificial liver.
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流动配置和膜特性对新型多同轴中空纤维生物人工肝膜污染的影响。
DOI：
10.1111/j.1749-6632.2001.tb03845.x
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发表时间：
2001
影响因子：
5.2
通讯作者：
Reid,LM
中科院分区：
文献类型：
--
作者：
MacDonald,JM;Wolfe,SP;Roy-Chowdhury,I;Kubota,H;Reid,LM
摘要：开发了一种新型“多同轴中空纤维生物反应器”，由四个同心管组成，最里面的两个管称为中空纤维。生物人工肝是通过在两个最里面的中空纤维之间的空间中培养肝祖细胞并使用夹在细胞室之间的两个室（毛细血管内和毛细血管外）中含有的培养基来创建的。最外面的隔室用于气体交换。最近建立了一个流体动力学模型来预测最佳水力渗透性和生物反应器操作参数，以创建肝腺泡中的物理化学环境。1然而，用无血清激素限定培养基灌注和细胞接种会在方程中引入膜污染，并且必须将该参数纳入模型中。使用市售的半透中空纤维（1 mm [0.65 μm 孔] 和 3 mm [0.1 μm 孔] 外径 [o.d]），阻力的主要原因是中间的中空纤维。使用接种离体大鼠肝细胞并灌注含血清培养基的生物反应器进行的初步研究表明，中间的中空纤维是主要的污垢部位，这种污垢通过阻碍营养物质的转移最终导致细胞死亡。我们进行了实验以确定用于构建生物反应器的最佳商用中空纤维，并对两种外径为 3 毫米的中空纤维进行了比较：聚丙烯和聚砜，孔径分别为 0.2 μm 和 0.1 μm。通过确定阻力随时间的变化，比较了死端和错流配置在减少中间中空纤维膜污染方面的有效性。结果表明，0.2μm孔径的聚丙烯中空纤维是构建多同轴中空纤维生物反应器的最佳选择，并且36小时后错流导致的阻力比死端流低两个数量级。
Abstract:A novel “multicoaxial hollow fiber bioreactor” has been developed consisting of four concentric tubes, the two innermost tubes are called hollow fibers. Bioartificial livers are created by culturing liver progenitors in the space between the two innermost hollow fibers and with culture media contained in the two compartments (intracapillary and extracapillary) sandwiching the cell compartment. The outermost compartment is used for gas exchange. A hydrodynamic model has recently been established to predict the optimum hydraulic permeability and bioreactor operational parameters to create the physicochemical environment found in the liver acinus.1 However, perfusion with serum‐free hormonally‐defined media and inoculation of cells introduces membrane fouling into the equation, and this parameter must be incorporated into the model. Using commercially available semipermeable hollow fibers (1 mm [0.65 μm pores] and 3 mm [0.1 μm pores] outer diameters [o.d]), the primary cause of resistance is the middle hollow fiber. Preliminary studies using bioreactors inoculated with isolated rat hepatocytes and perfused with serum‐containing culture media demonstrated that the middle hollow fiber is the primary site of fouling, and this fouling ultimately causes cell mortality by blocking the transfer of nutrients. Experiments were performed to determine the best commercially available middle hollow fiber for construction of bioreactors and two 3‐mm outer‐diameter middle hollow fibers were compared: polypropylene and polysulfone, with 0.2 μm and 0.1 μm pore sizes, respectively. Dead‐ended and cross flow configurations were compared for their effectiveness at reducing membrane fouling in the middle hollow fiber by determining the change in resistance with time. The results demonstrate that the 0.2‐μm pore size polypropylene hollow fiber is the best choice for construction of the multicoaxial hollow‐fiber bioreactor, and that cross flow results in two orders of magnitude lower resistance than dead‐ended flow after 36 h.
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DOI：
10.1016/0926-6585(65)90122-6
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