Chondrocyte deformations as a function of tibiofemoral joint loading predicted by a generalized high-throughput pipeline of multi-scale simulations.
Chondrocyte deformations as a function of tibiofemoral joint loading predicted by a generalized high-throughput pipeline of multi-scale simulations.
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DOI：
10.1371/journal.pone.0037538
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Erdemir A
中科院分区：
文献类型：
--
作者：
Sibole SC;Erdemir A
已知肌肉骨骼系统的细胞对机械负荷作出反应，并且软骨内的软骨细胞也不例外。然而，理解关节水平载荷如何与细胞水平变形（例如，在软骨中）相关并不是一项简单的任务。在这项研究中，多尺度分析流水线进行后处理的宏观尺度有限元（FE）胫股关节模型的结果，提供关节力学为基础的位移边界条件的软骨的微观细胞有限元模型，为表征软骨细胞变形与胫股关节负荷的目的。可以确定膝关节内组织结构之间的载荷分布，并最终确定软骨内细胞外基质、细胞周围环境和常驻软骨细胞之间的载荷分布。计算了各种细胞变形度量（纵横比变化、体积应变、细胞有效应变和最大剪切应变）。为了进一步说明这种多尺度建模管道的实用性，考虑了两种微尺度软骨结构：在过去研究中常用的100×100×100 μm块的质心处的理想化单细胞，以及胫股软骨中间区的基于解剖学的（相同体积的11个细胞模型）表示。在这两种情况下，软骨细胞经历了放大变形相比，在宏观尺度上，预测模拟一个体重的压缩载荷的胫股关节。在11个单元的情况下，所有单元经历比单个单元的情况下更少的变形，并且与位于同一块中的其他单元相比，还表现出更大的变形变化。耦合方法被证明是高度可扩展的，由于微尺度模型的独立性，允许利用分布式内存计算架构。该方法的广义性质也允许替代任何宏观尺度和/或微观尺度的模型提供其他多尺度连续介质力学问题的应用。
Cells of the musculoskeletal system are known to respond to mechanical loading and chondrocytes within the cartilage are not an exception. However, understanding how joint level loads relate to cell level deformations, e.g. in the cartilage, is not a straightforward task. In this study, a multi-scale analysis pipeline was implemented to post-process the results of a macro-scale finite element (FE) tibiofemoral joint model to provide joint mechanics based displacement boundary conditions to micro-scale cellular FE models of the cartilage, for the purpose of characterizing chondrocyte deformations in relation to tibiofemoral joint loading. It was possible to identify the load distribution within the knee among its tissue structures and ultimately within the cartilage among its extracellular matrix, pericellular environment and resident chondrocytes. Various cellular deformation metrics (aspect ratio change, volumetric strain, cellular effective strain and maximum shear strain) were calculated. To illustrate further utility of this multi-scale modeling pipeline, two micro-scale cartilage constructs were considered: an idealized single cell at the centroid of a 100×100×100 μm block commonly used in past research studies, and an anatomically based (11 cell model of the same volume) representation of the middle zone of tibiofemoral cartilage. In both cases, chondrocytes experienced amplified deformations compared to those at the macro-scale, predicted by simulating one body weight compressive loading on the tibiofemoral joint. In the 11 cell case, all cells experienced less deformation than the single cell case, and also exhibited a larger variance in deformation compared to other cells residing in the same block. The coupling method proved to be highly scalable due to micro-scale model independence that allowed for exploitation of distributed memory computing architecture. The method’s generalized nature also allows for substitution of any macro-scale and/or micro-scale model providing application for other multi-scale continuum mechanics problems.
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