Department of Bio-Medical Engineering, Technion - Institute of Technology, Haifa, Israel.
Biotechnol Bioeng. 2010 Feb 15;105(3):645-54. doi: 10.1002/bit.22555.
Novel tissue-culture bioreactors employ flow-induced shear stress as a means of mechanical stimulation of cells. We developed a computational fluid dynamics model of the complex three-dimensional (3D) microstructure of a porous scaffold incubated in a direct perfusion bioreactor. Our model was designed to predict high shear-stress values within the physiological range of those naturally sensed by vascular cells (1-10 dyne/cm(2)), and will thereby provide suitable conditions for vascular tissue-engineering experiments. The model also accounts for cellular growth, which was designed as an added cell layer grown on all scaffold walls. Five model variants were designed, with geometric differences corresponding to cell-layer thicknesses of 0, 50, 75, 100, and 125 microm. Four inlet velocities (0.5, 1, 1.5, and 2 cm/s) were applied to each model. Wall shear-stress distribution and overall pressure drop calculations were then used to characterize the relation between flow rate, shear stress, cell-layer thickness, and pressure drop. The simulations showed that cellular growth within 3D scaffolds exposes cells to elevated shear stress, with considerably increasing average values in correlation to cell growth and inflow velocity. Our results provide in-depth analysis of the microdynamic environment of cells cultured within 3D environments, and thus provide advanced control over tissue development in vitro.
新型组织培养生物反应器采用流动诱导剪切力作为细胞机械刺激的手段。我们开发了一种多孔支架的复杂三维（3D）微结构的计算流体动力学模型，该支架在直接灌注生物反应器中孵育。我们的模型旨在预测生理范围内的高剪切应力值，这些值是血管细胞自然感知到的（1-10 达因/平方厘米），从而为血管组织工程实验提供合适的条件。该模型还考虑了细胞生长，这被设计为在所有支架壁上生长的附加细胞层。设计了五个模型变体，其几何差异对应于细胞层厚度为 0、50、75、100 和 125 微米。每个模型都施加了四个入口速度（0.5、1、1.5 和 2 厘米/秒）。然后使用壁面剪切应力分布和总压降计算来表征流速、剪切应力、细胞层厚度和压降之间的关系。模拟结果表明，3D 支架内的细胞生长使细胞暴露于升高的剪切应力下，与细胞生长和流入速度相关的平均剪切应力值显著增加。我们的结果提供了对 3D 环境中培养的细胞的微动态环境的深入分析，从而提供了对体外组织发育的先进控制。
