Orthopaedic Biomechanics, Department of Biomedical Engineering, Eindhoven University of Technology, PO Box 513, 5600 MB , Eindhoven, The Netherlands,
Biomech Model Mechanobiol. 2013 Oct;12(5):901-13. doi: 10.1007/s10237-012-0452-1. Epub 2012 Nov 18.
The insufficient load-bearing capacity of today's tissue- engineered (TE) cartilage limits its clinical application. Generally, cartilage TE studies aim to increase the extracellular matrix (ECM) content, as this is thought to determine the load-bearing properties of the cartilage. However, there are apparent inconsistencies in the literature regarding the correlation between ECM content and mechanical properties of TE constructs. In addition to the amount of ECM, the spatial inhomogeneities in ECM distribution at the tissue scale as well as at the cell scale may affect the mechanical properties of TE cartilage. The relative importance of such structural inhomogeneities on mechanical behavior of TE cartilage is unknown. The aim of the present study was, therefore, to theoretically elucidate the influence of these inhomogeneities on the mechanical behavior of chondrocyte-agarose TE constructs. A validated non-linear fiber-reinforced poro-elastic swelling cartilage model that can accommodate for effects of collagen reinforcement and swelling by proteoglycans was used. At the tissue scale, ECM was gradually varied from predominantly localized in the periphery of the TE construct toward an ECM-rich inner core. The effect of these inhomogeneities in relation to the total amount of ECM was also evaluated. At the cell scale, ECM was gradually varied from localized in the pericellular area, toward equally distributed throughout the interterritorial area. Results from the tissue-scale model indicated that localization of ECM in either the construct periphery or in the inner core may reduce construct stiffness compared with that of constructs with homogeneous ECM. Such effects are more significant at high ECM amounts. At the cell scale, localization of ECM around the cells significantly reduced the overall stiffness, even at low ECM amounts. The compressive stiffness gradually increased when ECM distribution became more homogeneous and the osmotic swelling pressure in the interterritorial area increased. We conclude that for the same amount of ECM content in TE cartilage constructs, superior mechanical properties can be achieved with more homogeneous ECM distribution at both tissue and cell scale. Inhomogeneities at the cell scale are more important than those at the tissue scale.
今天的组织工程（TE）软骨的承载能力不足限制了其临床应用。一般来说，软骨 TE 研究旨在增加细胞外基质（ECM）含量，因为这被认为决定了软骨的承载特性。然而，在关于 TE 构建体的 ECM 含量与机械性能之间的相关性的文献中存在明显的不一致。除了 ECM 的数量外，在组织尺度和细胞尺度上 ECM 分布的空间不均匀性也可能影响 TE 软骨的机械性能。这些结构不均匀性对 TE 软骨机械性能的相对重要性尚不清楚。因此，本研究的目的是从理论上阐明这些不均匀性对软骨细胞-琼脂糖 TE 构建体的机械行为的影响。使用了一种经过验证的非线性纤维增强多孔弹性肿胀软骨模型，该模型可以适应胶原蛋白增强和蛋白聚糖肿胀的影响。在组织尺度上，ECM 逐渐从 TE 构建体的外围主要分布变为 ECM 丰富的内部核心。还评估了这些不均匀性与 ECM 总量的关系。在细胞尺度上，ECM 逐渐从细胞周围区域的局部化变为均匀分布在细胞间区域。组织尺度模型的结果表明，与 ECM 均匀分布的构建体相比，ECM 位于构建体外围或内部核心的定位可能会降低构建体的刚度。在 ECM 数量较高时，这种影响更为显著。在细胞尺度上，即使在 ECM 数量较低的情况下，ECM 在细胞周围的定位也会显著降低整体刚度。当 ECM 分布变得更加均匀并且细胞间区域中的渗透膨胀压力增加时，压缩刚度逐渐增加。我们得出结论，对于 TE 软骨构建体中相同的 ECM 含量，在组织和细胞尺度上具有更均匀的 ECM 分布可以获得更好的机械性能。细胞尺度上的不均匀性比组织尺度上的更重要。
