School of Chemical Engineering, Oklahoma State University, Stillwater, OK 74078, USA.
Biotechnol Prog. 2012 Jul;28(4):1045-54. doi: 10.1002/btpr.1547. Epub 2012 May 21.
In this study, transport characteristics in flow-through and parallel-flow bioreactors used in tissue engineering were simulated using computational fluid dynamics. To study nutrient distribution and consumption by smooth muscle cells colonizing the 100 mm diameter and 2-mm thick scaffold, effective diffusivity of glucose was experimentally determined using a two-chambered setup. Three different concentrations of chitosan-gelatin scaffolds were prepared by freezing at -80°C followed by lyophilization. Experiments were performed in both bioreactors to measure pressure drop at different flow rates. At low flow rates, experimental results were in agreement with the simulation results for both bioreactors. However, increase in flow rate beyond 5 mL/min in flow-through bioreactor showed channeling at the circumference resulting in lower pressure drop relative to simulation results. The Peclet number inside the scaffold indicated nutrient distribution within the flow-through bioreactor to be convection-dependent, whereas the parallel-flow bioreactor was diffusion-dependent. Three alternative design modifications to the parallel-flow were made by (i) introducing an additional inlet and an outlet, (ii) changing channel position, and (iii) changing the hold-up volume. Simulation studies were performed to assess the effect of scaffold thickness, cell densities, and permeability. These new designs improved nutrient distribution for 2 mm scaffolds; however, parallel-flow configuration was found to be unsuitable for scaffolds more than 4-mm thick, especially at low porosities as tissues regenerate. Furthermore, operable flow rate in flow-through bioreactors is constrained by the mechanical strength of the scaffold. In summary, this study showed limitations and differences between flow-through and parallel-flow bioreactors used in tissue engineering.
本研究采用计算流体力学模拟了组织工程中使用的流动式和并流式生物反应器中的传输特性。为了研究定殖在 100mm 直径和 2mm 厚支架上的平滑肌细胞对营养物质的分布和消耗情况，使用双室装置实验测定了葡萄糖的有效扩散系数。通过在-80°C 下冷冻然后冻干制备了三种不同浓度的壳聚糖-明胶支架。在两种生物反应器中进行实验以测量不同流速下的压降。在低流速下，两种生物反应器的实验结果与模拟结果吻合良好。然而，在流动式生物反应器中，流速增加到 5mL/min 以上时，在圆周处出现了通道现象，导致压降低于模拟结果。支架内的佩克莱数表明，流动式生物反应器中的营养物质分布取决于对流，而平行流式生物反应器则取决于扩散。对平行流式生物反应器进行了三种设计修改：（i）增加一个入口和一个出口；（ii）改变通道位置；（iii）改变持液量。进行了模拟研究以评估支架厚度、细胞密度和渗透性的影响。这些新设计改善了 2mm 支架的营养物质分布；然而，平行流配置被发现不适合厚度超过 4mm 的支架，尤其是在组织再生时，低孔隙率下更是如此。此外，流动式生物反应器的可操作流速受到支架机械强度的限制。总之，本研究表明了组织工程中使用的流动式和并流式生物反应器之间的局限性和差异。
