Development of rolled scaffold for high-density adherent cell culture

Development of rolled scaffold for high-density adherent cell culture
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用于高密度贴壁细胞培养的卷式支架的开发

DOI:
10.1007/s10544-019-0459-9
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发表时间:
2020
影响因子:
2.8
通讯作者:
Park, Kidong
Park, Kidong
中科院分区:
工程技术3区
文献类型:
--
作者:
YekrangSafakar, Ashkan;Hamel, Katie M.;Mehrnezhad, Ali;Jung, Jangwook P.;Park, Kidong

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用于大规模培养哺乳动物细胞的生物反应器在生物技术和生物工程中发挥着重要作用。已经开发了各种生物反应器,但它们的容量和效率通常受到传质速率不足和高剪切应力的限制。滚动支架(RS)是一种用于哺乳动物细胞高密度贴壁培养的完全定义的支架。RS是一种带有间隔物的聚合物薄膜,它被卷成一个圆柱体,每圈之间有预定的间隙。细胞在其内表面上培养,而培养基流过差距。RS具有超过100 cm 2/mL的高表面积与体积比,并且可以通过单向层流中的对流而不是搅拌罐生物反应器中的扩散和随机湍流来输送营养物和气体,剪切应力显著降低。本文采用RS生物反应器扩增中国人卵巢细胞,细胞培养密度超过6000万个/mL,生长速度高于常规悬浮培养。此外,小鼠胚胎干细胞成功地扩增,而不失去其多能性。RS将为生物制药行业中的重组细胞和组织工程中的剪切敏感干细胞的大规模培养提供负担得起的,可扩展的和可靠的平台。
Bioreactors for large-scale culture of mammalian cells are playing vital roles in biotechnology and bioengineering. Various bioreactors have been developed, but their capacity and efficiency are often limited by insufficient mass transfer rate and high shear stress. A rolled scaffold (RS) is a fully defined scaffold for high-density adherent culture of mammalian cells. The RS is a polymer film with spacers, that is rolled into a cylinder with a pre-determined gap between each turn. Cells are cultured on its inner surfaces, while media flows through the gap. The RS exhibits high surface-area-to-volume ratio over 100 cm2/mL and can transport nutrients and gases with significantly reduced shear stress via convection in a unidirectional laminar flow, rather than diffusion and random turbulent flow as in stirred-tank bioreactors. In this paper, we expanded Chinese Hamster Ovary cells with RS bioreactors and demonstrated cell culture density over 60 million cells/mL with a growth rate higher than conventional suspension culture. Besides, murine embryonic stem cells were successfully expanded without losing their pluripotency. The RS will provide an affordable, scalable, and reliable platform for large-scale culture of recombinant cells in biopharmaceutical industries and shear-sensitive stem cells for tissue engineering.
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