The cell-matrix mechano-electrochemical interactions in articular cartilage: Experiment and triphasic model

The overall goal of this thesis was to investigate the cell-matrix mechano-electrochemical (MEC) interactions in articular cartilage in order to gain a better understanding of the underlying mechanisms of the cell MEC transductions that is necessary for successful outcomes in regenerating functional tissue. To accomplish this overall goal, theoretical models based on the triphasic theory, which is currently the most advanced theoretical framework for biological tissue, were used to analyze experimental data obtained from carefully designed experimental apparatus and testing protocols. Constitutive models of the chondrocyte and the surrounding matrices including the cartilage tissue and agarose gel were first developed aiming to accurately describe mechanisms underlying their complex behaviors, which are the necessary foundation for the cell-matrix interaction analyses. The triphasic, conewise linear elasticity model was chosen to simultaneously account for the tension-compression nonlinearity of cartilage matrix and the tissue electrochemical behaviors given rise by the interplay of mobile ions and fixed negative charges. The chondrocyte was also modeled as a triphasic mixture aiming to describe their complex mechanical, electrical and chemical behaviors, and to investigate the osmotic effects on the cell apparent properties. Based on the knowledge on constitutive models and material properties of the cell and the matrix, the triphasic multi-scale finite element model of the cell-matrix interaction was created to address the complexity of the large differences between the tissue and the cell scales, and their material properties. Finally, a direct investigation on the cell-matrix MEC interactions was performed by validating the theoretical calculations with experimental data on the transient deformation of chondrocytes in situ within cartilage under unconfined compression, which were obtained from a specially-designed compression device interfacing fluorescence microscopy imaging. The major contribution of this thesis has been the coupling between advanced theoretical model and sophisticated experimental set up that provided a powerful framework essential for meaningful analyses of the cell-matrix interactions, which will potentially lead to a breakthrough in understanding of the cell MEC transduction mechanisms.