An in-silico approach to meniscus tissue regeneration: Modeling, numerical simulation, and experimental analysis

Elise Grosjean, Alex Keilmann, Henry Jäger, Shimi Mohanan, Claudia Redenbach, Bernd Simeon, Christina Surulescu, Luisa de Roy, Andreas Seitz, Graciosa Teixeira, Martin Dauner, Carsten Linti, Günter Schmidt
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Abstract

We develop a model the dynamics of human mesenchymal stem cells (hMSCs) and chondrocytes evolving in a nonwoven polyethylene terephtalate (PET) scaffold impregnated with hyaluron and supplied with a differentiation medium. The scaffold and the cells are assumed to be contained in a bioreactor with fluid perfusion. The differentiation of hMSCs into chondrocytes favors the production of extracellular matrix (ECM) and is influenced by fluid stress. The model takes deformations of ECM and PET scaffold into account. The scaffold structure is explicitly included by statistical assessment of the fibre distribution from CT images. The effective macroscopic equations are obtained by appropriate upscaling from dynamics on lower (microscopic and mesoscopic) scales and feature in the motility terms an explicit cell diffusion tensor encoding the assessed anisotropic scaffold structure. Numerical simulations show its influence on the overall cell and tissue dynamics.
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半月板组织再生的模拟方法:建模、数值模拟和实验分析
我们建立了一个人类间充质干细胞(hMSCs)和软骨细胞在用透明质酸浸渍并提供分化培养基的无纺布聚对苯二甲酸乙二醇酯(PET)支架中进化的动力学模型。假定支架和细胞都包含在有液体灌注的生物反应器中。hMSCs 向软骨细胞的分化有利于细胞外基质(ECM)的生成,并受到流体应力的影响。该模型考虑了 ECM 和 PET 支架的变形。通过对 CT 图像中纤维分布的统计评估,支架结构被明确包括在内。通过对较低(微观和中观)尺度的动力学进行适当的放大,得到了有效的宏观方程,并在运动项中加入了一个明确的细胞扩散张量,该张量对评估的各向异性支架结构进行了编码。数值模拟显示了它对整个细胞和组织动力学的影响。
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