模型预测径向通量分布对轴对称径向流填料床生物反应器中培养的构建体的氧气和葡萄糖细胞周浓度的影响

IF 5.3 2区 医学 Q1 ENGINEERING, BIOMEDICAL
Giuseppe Morrone , Gionata Fragomeni , Danilo Donato , Giuseppe Falvo D’Urso Labate , Luigi De Napoli , Charlotte Debbaut , Patrick Segers , Gerardo Catapano
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引用次数: 0

摘要

径向流填料床生物反应器(rPBB)克服了静态和轴向流灌注生物反应器的传输限制,使临床规模的生物工程组织的开发成为可能。我们制定了设计 rPBB 的标准,使其沿生物反应器长度方向具有均匀的介质径向通量分布,确保均匀的构建灌注。我们报告了基于模型的介质径向通量非均匀轴向分布对细胞周围氧气和葡萄糖浓度影响的分析。尽管该模型是假均质的,但它预测了介质通量、溶质运输和细胞消耗如何相互作用,并在存在孔隙运输阻力的情况下决定细胞周围的氧气和葡萄糖浓度,从而设计出最佳的轴对称 rPBB,并实现对细胞周围环境的控制。因此,随着组织的成熟,氧气和葡萄糖的供应可以满足细胞的需求。生物反应器空隙和构造物中的流动和溶质传输分别用纳维-斯托克斯方程和达西-布林克曼方程,以及对流-扩散方程和对流-扩散-反应方程来描述。构筑物中的溶质迁移考虑了迈克尔细胞消耗和大量介质到细胞表面的氧迁移阻力,即拉希格环的迁移等效床。在典型的组织工程操作下,预测了相关无量纲组对细胞周围和体积溶质浓度的影响,并根据骨组织工程的文献数据进行了评估。培养基径向通量的轴向分布影响细胞周溶质浓度的分布,在细胞代谢活性高时影响更大。介质进料流速的增加缓解了溶质浓度的不均匀分布,细胞表面的代谢消耗也从轴向不均匀径向通量分布开始衰减。模型预测的运行时间与在线控制策略兼容。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Model-predicted effect of radial flux distribution on oxygen and glucose pericellular concentration in constructs cultured in axisymmetric radial-flow packed-bed bioreactors

Radial flow packed-bed bioreactors (rPBBs) overcome the transport limitations of static and axial-flow perfusion bioreactors and enable development of clinical-scale bioengineered tissues. We developed criteria to design rPBBs with uniform medium radial flux distribution along bioreactor length ensuring uniform construct perfusion. We report a model-based analysis of the effect of non-uniform axial distribution of medium radial flux on pericellular concentration of oxygen and glucose. Albeit pseudo-homogeneous, the model predicts how medium flux, solutes transport and cellular consumption interact and determine the pericellular oxygen and glucose concentrations in the presence of pore transport resistance to design optimal axisymmetric rPBBs and enable control of pericellular environment. Thus, oxygen and glucose supply may match cell requirements as tissue matures. Flow and solute transport in bioreactor empty spaces and construct was described with Navier-Stokes and Darcy-Brinkman equations, and with convection–diffusion and convection–diffusion-reaction equations, respectively. Solute transport in construct accounted for Michaelian cellular consumption and bulk medium-to-cell surface oxygen transport resistance in terms of a transport-equivalent bed of Raschig rings. The effect of relevant dimensionless groups on pericellular and bulk solute concentrations was predicted under typical tissue engineering operation and evaluated against literature data for bone tissue engineering. Axial distribution of medium radial flux influenced the distribution of pericellular solutes concentration, more so at high cell metabolic activity. Increasing medium feed flow rates relieved non-uniform solute concentration distribution and decayed at cell surface for metabolic consumption, also starting from axially non-uniform radial flux distribution. Model predictions were obtained in runtimes compatible with on-line control strategies.

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来源期刊
CiteScore
16.50
自引率
6.20%
发文量
77
审稿时长
38 days
期刊介绍: Biocybernetics and Biomedical Engineering is a quarterly journal, founded in 1981, devoted to publishing the results of original, innovative and creative research investigations in the field of Biocybernetics and biomedical engineering, which bridges mathematical, physical, chemical and engineering methods and technology to analyse physiological processes in living organisms as well as to develop methods, devices and systems used in biology and medicine, mainly in medical diagnosis, monitoring systems and therapy. The Journal''s mission is to advance scientific discovery into new or improved standards of care, and promotion a wide-ranging exchange between science and its application to humans.
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