YekrangSafakar Ashkan, Mehrnezhad Ali, Wu Tongyao, Park Kidong
Division of Electrical and Computer Engineering, Louisiana State University, Baton Rouge, Louisiana, USA.
Biotechnol Bioeng. 2022 Jun;119(6):1498-1508. doi: 10.1002/bit.28079. Epub 2022 Apr 2.
Rapid expansion of biopharmaceutical market calls for more efficient and reliable platforms to culture mammalian cells on a large scale. Stirred-tank bioreactors have been widely used for large-scale cell culture. However, it requires months of trials and errors to optimize culture conditions for each cell line. In this article, we extend our earlier studies on rolled scaffold (RS) bioreactors for high-density adherent cell culture and report two new implementations of RSs with greatly enhanced mass-manufacturability, termed as Mesh-RS and Fiber-RS. CHO-K1 cells were successfully expanded in Mesh-RS and Fiber-RS bioreactors with an average growth rate of 1.09 ± 0.04 1/day and 0.95 ± 0.07 1/day, which were higher than those reported in similar studies. Fiber-RS bioreactor exhibited a very high cell density of 72.8 × 10 cells/ml. Besides, a dialyzer was integrated into the RS bioreactor to remove cellular waste and to replenish nutrients without disturbing the cells. By collecting the dialyzed media separately, the dialysis efficiency was significantly improved. In conclusion, the developed RS bioreactor has a strong potential to provide a highly reliable and easily scalable platform for large-scale cell culture in the biopharmaceutical industry.
生物制药市场的迅速扩张需要更高效、可靠的平台来大规模培养哺乳动物细胞。搅拌罐式生物反应器已广泛用于大规模细胞培养。然而，为每种细胞系优化培养条件需要数月的反复试验。在本文中，我们扩展了早期关于用于高密度贴壁细胞培养的滚动支架（RS）生物反应器的研究，并报告了两种具有大大提高的大规模制造能力的RS新实施方案，称为网状RS和纤维RS。CHO-K1细胞在网状RS和纤维RS生物反应器中成功扩增，平均生长速率分别为1.09±0.04 1/天和0.95±0.07 1/天，高于类似研究中报道的生长速率。纤维RS生物反应器表现出非常高的细胞密度，为72.8×10 个细胞/毫升。此外，将透析器集成到RS生物反应器中，以去除细胞废物并补充营养，而不会干扰细胞。通过分别收集透析后的培养基，透析效率显著提高。总之，所开发的RS生物反应器具有强大的潜力，可为生物制药行业的大规模细胞培养提供高度可靠且易于扩展的平台。
