Institute of Bioengineering, School of Engineering and Materials Science, Queen Mary University of London, London, UK.
Faculty of Health Sciences, University of Southampton, UK.
Clin Biomech (Bristol). 2020 Oct;79:104972. doi: 10.1016/j.clinbiomech.2020.01.022. Epub 2020 Feb 8.
Mechanical conditioning has been widely used to attempt to enhance chondrocyte metabolism for the evolution of functionally competent cartilage. However, although upregulation of proteoglycans have been reported through the application of uniaxial compression, minimal collagen has been produced. The study is designed to examine whether alternative loading regimens, equivalent to physiological conditions, involving shear in addition to compression can enhance collagen production.
Finite element models were developed to determine how the local chondrocyte environments within agarose constructs were influenced by a range of static and dynamic loading regimens. 3-D poro-viscoelastic models were validated against experimental data. In particular, these models were used to characterise chondrocyte deformation in compression with and without shear superimposed, with special reference to the formation of pericellular matrix around the cells.
The models of the hydrogel constructs under stress relaxation and dynamic cyclic compression conditions were highly correlated with the experimental data. The cell deformation (y/z) in the constructs was greatest in the centre of the constructs, increasing with magnitude of compression up to 25%. The superposition of shear however did not produce significant additional changes in deformation, with the presence of PCM reducing the chondrocyte deformation.
The use of FE models can prove important in the definition of appropriate, optimised mechanical conditioning regimens for the synthesis and organisation of mature extra cellular matrix by chondrocyte-seeded constructs. They will also provide insight into the mechanisms relating cell deformation to mechanotransduction pathways, thereby progressing the development of functionally competent tissue engineered cartilage.
机械处理已广泛用于尝试增强软骨细胞代谢，以促进功能成熟的软骨形成。然而，尽管已有研究报道称，单轴压缩能上调蛋白聚糖，但胶原蛋白的产生量却很少。本研究旨在探讨替代加载方案（除压缩外还包括剪切）是否能增加胶原蛋白的产生，这些方案相当于生理条件。
开发了有限元模型，以确定琼脂糖构建体中局部软骨细胞环境如何受到一系列静态和动态加载方案的影响。三维多孔粘弹性模型通过实验数据进行了验证。特别是，这些模型用于描述有和没有剪切叠加的压缩条件下软骨细胞的变形，特别关注细胞周围细胞外基质的形成。
在应力松弛和动态循环压缩条件下的水凝胶构建体模型与实验数据高度相关。构建体中细胞的变形（y/z）在构建体的中心最大，随着压缩量的增加到 25%而增加。然而，剪切的叠加并没有产生显著的额外变形变化，PCM 的存在减少了软骨细胞的变形。
FE 模型的使用对于定义适当的机械处理方案以促进软骨细胞接种构建体中成熟细胞外基质的合成和组织非常重要。它们还将深入了解与细胞变形相关的机械转导途径的机制，从而推进功能成熟的组织工程软骨的发展。
