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在基于µCT和CAD的快速原型支架模型表面模拟机械信号,以预测(早期)组织发育。

Modeling mechanical signals on the surface of µCT and CAD based rapid prototype scaffold models to predict (early stage) tissue development.

作者信息

Hendrikson W J, van Blitterswijk C A, Verdonschot N, Moroni L, Rouwkema J

机构信息

Department of Tissue Regeneration, University of Twente, Enschede, 7500 AE, Overijssel, The Netherlands.

出版信息

Biotechnol Bioeng. 2014 Sep;111(9):1864-75. doi: 10.1002/bit.25231. Epub 2014 May 13.

Abstract

In the field of tissue engineering, mechano-regulation theories have been applied to help predict tissue development in tissue engineering scaffolds in the past. For this, finite element models (FEMs) were used to predict the distribution of strains within a scaffold. However, the strains reported in these studies are volumetric strains of the material or strains developed in the extracellular matrix occupying the pore space. The initial phase of cell attachment and growth on the biomaterial surface has thus far been neglected. In this study, we present a model that determines the magnitude of biomechanical signals on the biomaterial surface, enabling us to predict cell differentiation stimulus values at this initial stage. Results showed that magnitudes of the 2D strain--termed surface strain--were lower when compared to the 3D volumetric strain or the conventional octahedral shear strain as used in current mechano-regulation theories. Results of both µCT and CAD derived FEMs from the same scaffold were compared. Strain and fluid shear stress distributions, and subsequently the cell differentiation stimulus, were highly dependent on the pore shape. CAD models were not able to capture the distributions seen in the µCT FEM. The calculated mechanical stimuli could be combined with current mechanobiological models resulting in a tool to predict cell differentiation in the initial phase of tissue engineering. Although experimental data is still necessary to properly link mechanical signals to cell behavior in this specific setting, this model is an important step towards optimizing scaffold architecture and/or stimulation regimes.

摘要

在组织工程领域,过去机械调节理论已被应用于帮助预测组织工程支架中的组织发育。为此,有限元模型(FEM)被用于预测支架内的应变分布。然而,这些研究中报告的应变是材料的体积应变或在占据孔隙空间的细胞外基质中产生的应变。生物材料表面细胞附着和生长的初始阶段迄今一直被忽视。在本研究中,我们提出了一个模型,该模型可确定生物材料表面生物力学信号的大小,使我们能够预测这个初始阶段的细胞分化刺激值。结果表明,与三维体积应变或当前机械调节理论中使用的传统八面体剪应变相比,二维应变(称为表面应变)的大小更低。对来自同一支架的µCT和CAD衍生的有限元模型的结果进行了比较。应变和流体剪应力分布,以及随后的细胞分化刺激,高度依赖于孔隙形状。CAD模型无法捕捉µCT有限元模型中看到的分布。计算出的机械刺激可以与当前的力学生物学模型相结合,从而形成一种预测组织工程初始阶段细胞分化的工具。尽管在这种特定情况下,仍需要实验数据来将机械信号与细胞行为正确联系起来,但该模型是朝着优化支架结构和/或刺激方案迈出的重要一步。

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