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Development and Characterization of a Parallelizable Perfusion Bioreactor for 3D Cell Culture

机译:用于3D细胞培养的可并行灌注生物反应器的开发和表征

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摘要

The three dimensional (3D) cultivation of stem cells in dynamic bioreactor systems is essential in the context of regenerative medicine. Still, there is a lack of bioreactor systems that allow the cultivation of multiple independent samples under different conditions while ensuring comprehensive control over the mechanical environment. Therefore, we developed a miniaturized, parallelizable perfusion bioreactor system with two different bioreactor chambers. Pressure sensors were also implemented to determine the permeability of biomaterials which allows us to approximate the shear stress conditions. To characterize the flow velocity and shear stress profile of a porous scaffold in both bioreactor chambers, a computational fluid dynamics analysis was performed. Furthermore, the mixing behavior was characterized by acquisition of the residence time distributions. Finally, the effects of the different flow and shear stress profiles of the bioreactor chambers on osteogenic differentiation of human mesenchymal stem cells were evaluated in a proof of concept study. In conclusion, the data from computational fluid dynamics and shear stress calculations were found to be predictable for relative comparison of the bioreactor geometries, but not for final determination of the optimal flow rate. However, we suggest that the system is beneficial for parallel dynamic cultivation of multiple samples for 3D cell culture processes.
机译:在动态生物反应器系统中,干细胞的三维(3D)培养对于再生医学至关重要。仍然缺乏生物反应器系统,该系统允许在不同条件下培养多个独立样品,同时确保对机械环境的全面控制。因此,我们开发了具有两个不同生物反应器腔室的小型化,可并行化的灌注生物反应器系统。还采用了压力传感器来确定生物材料的渗透性,这使我们能够近似切应力条件。为了表征两个生物反应器室中多孔支架的流速和切应力分布,进行了计算流体动力学分析。此外,通过获得停留时间分布来表征混合行为。最后,在概念验证研究中评估了生物反应器腔室不同流量和切应力曲线对人间充质干细胞成骨分化的影响。总之,发现来自计算流体动力学和切应力计算的数据对于生物反应器几何形状的相对比较是可预测的,但对于最佳流速的最终确定却是不可预测的。但是,我们建议该系统对于3D细胞培养过程的多个样品的并行动态培养是有益的。

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