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用于大规模三维骨组织工程的中空纤维膜生物反应器中贴壁细胞生长的计算建模

Computational modeling of adherent cell growth in a hollow-fiber membrane bioreactor for large-scale 3-D bone tissue engineering.

作者信息

Mohebbi-Kalhori Davod, Behzadmehr Amin, Doillon Charles J, Hadjizadeh Afra

机构信息

Department of Chemical Engineering-Biotechnology, Université de Sherbrooke, 2500, Boulevard de l'Université, Sherbrooke, QC J1K 2R1, Canada.

出版信息

J Artif Organs. 2012 Sep;15(3):250-65. doi: 10.1007/s10047-012-0649-1. Epub 2012 May 19.

Abstract

The use of hollow-fiber membrane bioreactors (HFMBs) has been proposed for three-dimensional bone tissue growth at the clinical scale. However, to achieve an efficient HFMB design, the relationship between cell growth and environmental conditions must be determined. Therefore, in this work, a dynamic double-porous media model was developed to determine nutrient-dependent cell growth for bone tissue formation in a HFMB. The whole hollow-fiber scaffold within the bioreactor was treated as a porous domain in this model. The domain consisted of two interpenetrating porous regions, including a porous lumen region available for fluid flow and a porous extracapillary space filled with a collagen gel that contained adherent cells for promoting long-term growth into tissue-like mass. The governing equations were solved numerically and the model was validated using previously published experimental results. The contributions of several bioreactor design and process parameters to the performance of the bioreactor were studied. The results demonstrated that the process and design parameters of the HFMB significantly affect nutrient transport and thus cell behavior over a long period of culture. The approach presented here can be applied to any cell type and used to develop tissue engineering hollow-fiber scaffolds.

摘要

有人提出在临床规模上使用中空纤维膜生物反应器(HFMBs)来实现三维骨组织生长。然而,为了实现高效的HFMB设计,必须确定细胞生长与环境条件之间的关系。因此,在这项工作中,开发了一种动态双多孔介质模型,以确定HFMB中骨组织形成的营养依赖型细胞生长。在该模型中,生物反应器内的整个中空纤维支架被视为一个多孔区域。该区域由两个相互贯穿的多孔区域组成,包括一个可供流体流动的多孔内腔区域和一个充满胶原凝胶的多孔毛细血管外空间,胶原凝胶中含有贴壁细胞,用于促进细胞长期生长形成组织样团块。对控制方程进行了数值求解,并使用先前发表的实验结果对模型进行了验证。研究了几个生物反应器设计和工艺参数对生物反应器性能的影响。结果表明,HFMB的工艺和设计参数在长期培养过程中显著影响营养物质的运输,进而影响细胞行为。这里提出的方法可以应用于任何细胞类型,并用于开发组织工程中空纤维支架。

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