Abstract Bioreactor design is a challenging endeavour that aims to provide the most ideal environment in which cells can grow and biological reactions can occur. The emergence of regenerative medicine and stem cell therapies has led to the need for more diverse environmental requirements in the bioreactor design space. The study presented uses an additive manufacturing approach for the initial design phase of a packed/fluidized bed bioreactor for mesenchymal stem cell expansion. Combining 3D-printing with CFD for precision control over the bioreactor flow dynamics. Novel flow distributors were developed to engender swirling particle fluidization. The design was simulated and optimised using CFD, demonstrating an increase from 0.01 m/s to 0.02 m/s in the radial velocity of 3.0 mm macrocarriers (1080 kg/m3) at the minimum fluidization velocity. An autoclavable prototype was constructed to illustrate proof-of-concept in the use of swirling flow distribution to enhance cell attachment efficiency (compared to static culture system). Commercial Cytodex 1 carriers were tested: an improvement in attachment efficiency after 24 h from 50 % to 95 % was induced by the swirling flow distributor, with subsequent expansion of 2.4-fold after 6 days of culture. The computational design, modelling and 3D-printing of complex geometric architecture that control the flow dynamics within a bioreactor, provides a novel approach to bioprocess unit operation development for manufacturing novel ATMPs.

中文翻译：

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用于间充质干细胞培养的生物反应器设计的增材制造方法

摘要 生物反应器设计是一项具有挑战性的工作，旨在提供最理想的细胞生长和生物反应发生的环境。再生医学和干细胞疗法的出现导致对生物反应器设计空间的环境要求更加多样化。该研究介绍了在用于间充质干细胞扩增的填充/流化床生物反应器的初始设计阶段使用增材制造方法。将 3D 打印与 CFD 相结合，以精确控制生物反应器的流动动力学。开发了新型流量分配器以产生涡流颗粒流化。该设计使用 CFD 进行了模拟和优化，表明在最小流化速度下 3.0 mm 大载体 (1080 kg/m3) 的径向速度从 0.01 m/s 增加到 0.02 m/s。构建了一个可高压灭菌的原型，以说明使用旋流分布来提高细胞附着效率（与静态培养系统相比）的概念验证。测试了商用 Cytodex 1 载体：24 小时后的附着效率从 50% 提高到 95%，这是由旋流分配器诱导的，随后在培养 6 天后扩增了 2.4 倍。控制生物反应器内流动动力学的复杂几何结构的计算设计、建模和 3D 打印，为制造新型 ATMP 的生物过程单元操作开发提供了一种新方法。测试了商用 Cytodex 1 载体：24 小时后的附着效率从 50% 提高到 95%，这是由旋流分配器诱导的，随后在培养 6 天后扩增了 2.4 倍。控制生物反应器内流动动力学的复杂几何结构的计算设计、建模和 3D 打印，为制造新型 ATMP 的生物过程单元操作开发提供了一种新方法。测试了商用 Cytodex 1 载体：24 小时后的附着效率从 50% 提高到 95%，这是由旋流分配器诱导的，随后在培养 6 天后扩增了 2.4 倍。控制生物反应器内流动动力学的复杂几何结构的计算设计、建模和 3D 打印，为制造新型 ATMP 的生物过程单元操作开发提供了一种新方法。