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模拟流体通过用于灌注生物反应器的不规则支架的流动。

Modeling fluid flow through irregular scaffolds for perfusion bioreactors.

作者信息

Maes Frédéric, Van Ransbeeck Peter, Van Oosterwyck Hans, Verdonck Pascal

机构信息

Department of Mechanics, University College Ghent, Belgium.

出版信息

Biotechnol Bioeng. 2009 Jun 15;103(3):621-30. doi: 10.1002/bit.22277.

DOI:10.1002/bit.22277
PMID:19288440
Abstract

Direct perfusion of 3D tissue engineered constructs is known to enhance osteogenesis, which can be partly attributed to enhanced nutrient and waste transport. In addition flow mediated shear stresses are known to upregulate osteogenic differentiation and mineralization. A quantification of the hydrodynamic environment is therefore crucial to interpret and compare results of in vitro bioreactor experiments. This study aims to deal with the pitfalls of numerical model preparation of highly complex 3D bone scaffold structures and aims to provide more accurate wall shear stress (WSS) estimates. microCT imaging techniques were used to reconstruct the geometry of both a titanium (Ti) and a hydroxyapatite scaffold, starting from 430 images with a resolution of 8 microm. To tackle the tradeoff between model size and mesh resolution we selected two concentric regions of interest (cubes with a volume of 1 and 3.375 mm(3), respectively) for both scaffolds. A flow guidance in front of the real inlet surface of the scaffold was designed to mimic realistic inlet conditions. With a flow rate of 0.04 mL/min perfused through a 5 mm diameter scaffold at an inlet velocity of 33.95 microm/s we obtained average WSSs of 1.10 and 1.46 mPa for the 1 mm(3) and the 3.375 mm(3) model of the hydroxyapatite scaffold compared to 1.40 and 1.95 mPa for the 1 mm(3) model and the 3.375 mm(3) model of the Ti scaffold, showing the important influence of the scaffold micro-architecture heterogeneity and the proximity of boundaries. To assess that influence we selected cubic portions, of which the WSS data were analyzed, with the same size and the same location within both 1 and 3.375 mm(3) cubic models. Varying the size of the inner portions simultaneously in both model selections gives a quantification of the sensitivity to boundary neighborhood. This methodology allows to get more insight in the complex concept of tissue engineering and will likely help to understand and eventually improve the fluid-mechanical aspects.

摘要

已知对3D组织工程构建体进行直接灌注可增强骨生成,这部分可归因于营养物质和废物运输的增强。此外,已知流动介导的剪应力可上调成骨分化和矿化。因此,对流体动力学环境进行量化对于解释和比较体外生物反应器实验结果至关重要。本研究旨在解决高度复杂的3D骨支架结构数值模型制备中的陷阱,并旨在提供更准确的壁面剪应力(WSS)估计。使用microCT成像技术从430张分辨率为8微米的图像开始重建钛(Ti)支架和羟基磷灰石支架的几何形状。为了解决模型大小和网格分辨率之间的权衡,我们为两种支架选择了两个同心感兴趣区域(分别为体积为1和3.375 mm³的立方体)。在支架实际入口表面前方设计了流动引导,以模拟实际入口条件。以0.04 mL/min的流速通过直径5 mm的支架灌注,入口速度为33.95微米/秒,对于羟基磷灰石支架的1 mm³和3.375 mm³模型,我们获得的平均WSS分别为1.10和1.46 mPa,而对于Ti支架的1 mm³模型和3.375 mm³模型,平均WSS分别为1.40和1.95 mPa,这表明了支架微结构异质性和边界接近度的重要影响。为了评估这种影响,我们选择了立方部分,分析其WSS数据,这些立方部分在1和3.375 mm³立方模型中具有相同的大小和相同的位置。在两种模型选择中同时改变内部部分的大小,可以量化对边界邻域的敏感性。这种方法有助于更深入地了解组织工程的复杂概念,并可能有助于理解并最终改善流体力学方面。

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