The Dynamic Mechanical Environment of the Chondrocyte: A Biphasic Finite Element Model of Cell-Matrix Interactions Under Cyclic Compressive Loading

摘要

Cyclic mechanical loading of articular cartilage results in a complex biomechanical environment at the scale of the chondrocytes that strongly affects cellular metabolic activity. Under dynamic loading conditions, the quantitative relationships between macroscopic loading characteristics and solid and fluid mechanical variables in the local cellular environment are not well understood. In this study, an axisymmetric multiscale model of linear biphasic cell-matrix interactions in articular cartilage was developed to investigate the cellular microenvironment in an explant subjected to cyclic confined compressive loading. The model was based on the displacement-velocity-pressure (u-v-p) mixed-penalty weighted residual formulation of linear biphasic theory that was implemented in the COMSOL MULTIPHYSICS software package. The microscale cartilage environment was represented as a three-zone biphasic region consisting of a spherical chondrocyte with encapsulating pericellular matrix (PCM) that was embedded in a cylindrical extracellular matrix (ECM) subjected to cyclic confined compressive loading boundary conditions. Biphasic material properties for the chondrocyte and the PCM were chosen based on previous in vitro micropipette aspiration studies of cells or chondrons isolated from normal or osteoarthritic cartilage. Simulations performed at four loading frequencies in the range 0.01-1.0 Hz supported the hypothesized dual role of the PCM as both a protective layer for the cell and a mechanical transducer of strain. Time varying biphasic variables at the cellular scale were strongly dependent on relative magnitudes of the loading period, and the characteristic gel diffusion times for the ECM, the PCM, and the chondrocyte. The multiscale simulations also indicated that axial strain was significantly amplified in the range 0.01-1.0 Hz, with a decrease in amplification factor and frequency insensitivity at the higher frequencies. Simulations of matrix degradation due to osteoarthritis indicated that strain amplification factors were more significantly altered when loss of matrix stiffness was exclusive to the PCM. The findings of this study demonstrate the complex dependence of dynamic mechanics in the local cellular environment of cartilage on macroscopic loading features and material properties of the ECM and the chondron.