OCIAM, Mathematical Institute, University of Oxford, Andrew Wiles Building, Radcliffe Observatory Quarter, Woodstock Road, Oxford, OX2 6GG, UK.
Biomech Model Mechanobiol. 2015 Apr;14(2):387-402. doi: 10.1007/s10237-014-0611-7. Epub 2014 Sep 12.
We present a simplified two-dimensional model of fluid flow, nutrient transport and cell distribution in a hollow fibre membrane bioreactor, with the aim of exploring how fluid flow can be used to control the distribution and yield of a cell population which is sensitive to both fluid shear stress and nutrient concentration. The cells are seeded in a scaffold in a layer on top of the hollow fibre, only partially occupying the extracapillary space. Above this layer is a region of free-flowing fluid which we refer to as the upper fluid layer. The flow in the lumen and upper fluid layer is described by the Stokes equations, whilst the flow in the porous fibre membrane is assumed to follow Darcy's law. Porous mixture theory is used to model the dynamics of and interactions between the cells, scaffold and fluid in the cell-scaffold construct. The concentration of a limiting nutrient (e.g. oxygen) is governed by an advection-reaction-diffusion equation in each region. Through exploitation of the small aspect ratio of each region and asymptotic analysis, we derive a coupled system of partial differential equations for the cell volume fraction and nutrient concentration. We use this model to investigate the effect of mechanotransduction on the distribution and yield of the cell population, by considering cases in which cell proliferation is either enhanced or limited by fluid shear stress and by varying experimentally controllable parameters such as flow rate and cell-scaffold construct thickness.
我们提出了一种简化的二维模型,用于研究如何通过控制流体流动来控制对流体剪切应力和营养浓度敏感的细胞群体的分布和产量。该模型描述了中空纤维膜生物反应器中的流体流动、营养物质传输和细胞分布,其中细胞接种在中空纤维顶部的支架上的一层中,仅部分占据毛细血管外空间。在该层上方是一个自由流动的流体区域,我们称之为上流体层。管腔和上流体层中的流动由 Stokes 方程描述,而多孔纤维膜中的流动则假定遵循达西定律。多孔混合物理论用于模拟细胞、支架和细胞-支架结构中流体的动力学和相互作用。在每个区域中,通过对流-反应-扩散方程来控制限制营养物质(例如氧气)的浓度。通过利用每个区域的小纵横比和渐近分析,我们推导出了细胞体积分数和营养浓度的耦合偏微分方程组。我们使用该模型通过考虑由流体剪切应力增强或限制细胞增殖的情况以及通过改变实验可控制参数(例如流速和细胞-支架结构厚度)来研究机械转导对细胞群体分布和产量的影响。