Computational fluid dynamic characterization of vertical-wheel bioreactors used for effective scale-up of human induced pluripotent stem cell aggregate culture,The Canadian Journal of Chemical Engineering

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Computational fluid dynamic characterization of vertical-wheel bioreactors used for effective scale-up of human induced pluripotent stem cell aggregate culture
The Canadian Journal of Chemical Engineering ( IF 1.6 ) Pub Date : 2021-07-08 , DOI: 10.1002/cjce.24253
Tiffany Dang _{1,

2,

3} , Breanna S. Borys _{1,

2,

3,

4} , Shivek Kanwar _{1,

5} , James Colter _{1,

2,

3} , Hannah Worden ₄ , Abigail Blatchford ₄ , Matthew S. Croughan ₆ , Tareq Hossan ₇ , Derrick E. Rancourt ₇ , Brian Lee ₄ , Michael S. Kallos _{1,

2,

3} , Sunghoon Jung ₄

Affiliation

Bioreactor-based processes are the method of choice for efficient expansion of cells in a controlled setting. However, induced pluripotent stem cells (iPSCs) have proven to be extremely sensitive to the bioreactor hydrodynamic environment, making the use of suspension bioreactors to produce quality-assured cells at clinical and commercial scales very challenging. The PBS vertical-wheel (VW) bioreactor combines radial and axial flow components to produce uniform hydrodynamic force distributions, making it a promising platform to overcome the scale-up challenges associated with iPSCs. In this study, hydrodynamic characterization through computational fluid dynamics modelling of VW bioreactors was performed. Analysis of these models proved that important volume average hydrodynamic variables could be maintained throughout scale-up from the 0.1 L to the 15 L VW bioreactor scale. Each bioreactor scale (0.1, 0.5, 3, and 15 L) was modelled at a variety of agitation rates, leading to the generation of scale-up correlation equations. These equations allow operators to define a working range of hydrodynamic variables at one scale and calculate the corresponding agitation rates at other modelled scales. A suggested operating range of agitation rates was determined for the successful culture of iPSCs in the VW bioreactor at each scale, corresponding to constant volume average energy dissipation rate. Agitation rates from the 0.1 and 0.5 L VW bioreactor scale were experimentally tested to biologically validate the suggested range. High cell-fold expansion, healthy aggregate morphology, growth, and uniformity were demonstrated for all conditions tested within the suggested working range.

中文翻译：

用于有效放大人诱导多能干细胞聚集体培养的垂直轮生物反应器的计算流体动力学表征

基于生物反应器的过程是在受控环境中有效扩增细胞的首选方法。然而，诱导多能干细胞 (iPSC) 已被证明对生物反应器的流体动力学环境极其敏感，这使得使用悬浮生物反应器在临床和商业规模上生产质量有保证的细胞非常具有挑战性。PBS 垂直轮 (VW) 生物反应器结合了径向和轴向流动组件以产生均匀的水动力分布，使其成为克服与 iPSC 相关的放大挑战的有前途的平台。在这项研究中，通过 VW 生物反应器的计算流体动力学建模进行了流体动力学表征。对这些模型的分析证明，重要的体积平均水动力变量可以在从 0. 1 L 至 15 L VW 生物反应器规模。每个生物反应器规模（0.1、0.5、3 和 15 L）都在各种搅拌速率下建模，从而生成放大相关方程。这些方程允许操作员在一个尺度上定义流体动力学变量的工作范围，并在其他建模尺度下计算相应的搅拌速率。为在大众生物反应器中成功培养 iPSCs 在每个规模上确定了建议的搅拌速率操作范围，对应于恒定的体积平均能量耗散率。对 0.1 和 0.5 L VW 生物反应器规模的搅拌速率进行了实验测试，以从生物学上验证建议的范围。在建议的工作范围内测试的所有条件都证明了高细胞倍数扩增、健康的聚集体形态、生长和均匀性。

更新日期：2021-07-08

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