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计算建模预测组织工程支架中的微机械环境。

Computational modeling to predict the micromechanical environment in tissue engineering scaffolds.

机构信息

Department of Mechanical Engineering, Colorado State University, Ft Collins, CO, USA.

School of Biomedical Engineering, Colorado State University, Ft Collins, CO, USA.

出版信息

J Biomech. 2021 May 7;120:110355. doi: 10.1016/j.jbiomech.2021.110355. Epub 2021 Mar 2.

DOI:10.1016/j.jbiomech.2021.110355
PMID:33711600
Abstract

Cell fate in tissue engineering (TE) strategies is paramount to regenerate healthy, functional organs. The mechanical loads experienced by cells play an important role in cell fate. However, in TE scaffolds with a cell-laden hydrogel matrix, it is prohibitively complex to prescribe and measure this cellular micromechanical environment (CME). Accordingly, this study aimed to develop a finite element (FE) model of a TE scaffold unit cell that can be subsequently implemented to predict the CME and cell fates under prescribed loading. The compressible hyperelastic mechanics of a fibrin hydrogel were characterized by fitting unconfined compression and confined compression experimental data. This material model was implemented in a unit cell FE model of a TE scaffold. The FE mesh and boundary conditions were evaluated with respect to the mechanical response of a region of interest (ROI). A compressible second-order reduced polynomial hyperelastic model gave the best fit to the experimental data (C = 1.72 × 10, C = 3.83 × 10, D = 3.41, D = 8.06 × 10). A mesh with seed sizes of 40 µm and 60 µm in the ROI and non-ROI regions, respectively, yielded a converged model in 54 min. The in-plane boundary conditions demonstrated minimal influence on ROI mechanics for a 2-by-2 unit cell. However, the out-of-plane boundary conditions did exhibit an appreciable influence on ROI mechanics for a two bilayer unit cell. Overall, the developed unit cell model facilitates the modeling of the mechanical state of a cell-laden hydrogel within a TE scaffold under prescribed loading. This model will be utilized to characterize the CME in future studies, and 3D micromechanical criteria may be applied to predict cell fate in these scaffolds.

摘要

组织工程 (TE) 策略中的细胞命运对于再生健康、功能器官至关重要。细胞所经历的机械负荷在细胞命运中起着重要作用。然而,在含有细胞的水凝胶基质的 TE 支架中,规定和测量这种细胞微机械环境 (CME) 非常复杂。因此,本研究旨在开发一种可用于预测规定载荷下 CME 和细胞命运的 TE 支架单元细胞有限元 (FE) 模型。通过拟合无约束压缩和约束压缩实验数据,对纤维蛋白水凝胶的可压缩超弹性力学进行了表征。该材料模型被应用于 TE 支架的单元细胞 FE 模型中。FE 网格和边界条件是根据感兴趣区域 (ROI) 的力学响应进行评估的。可压缩二阶简化多项式超弹性模型与实验数据拟合最好 (C = 1.72×10,C = 3.83×10,D = 3.41,D = 8.06×10)。在 ROI 和非 ROI 区域中,种子大小分别为 40 µm 和 60 µm 的网格在 54 分钟内产生了收敛模型。对于 2×2 单元细胞,面内边界条件对 ROI 力学的影响最小。然而,对于两层单元细胞,面外边界条件确实对 ROI 力学有明显影响。总体而言,开发的单元细胞模型有助于在规定载荷下对细胞负载水凝胶在 TE 支架中的机械状态进行建模。该模型将用于未来研究中 CME 的表征,并且 3D 微观力学标准可用于预测这些支架中的细胞命运。

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引用本文的文献

1
High throughput computational evaluation of how scaffold architecture, material selection, and loading modality influence the cellular micromechanical environment in tissue engineering strategies.关于支架结构、材料选择和加载方式如何影响组织工程策略中细胞微机械环境的高通量计算评估。
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