Structural Integrity of Extracellular Matrix Influences the Mechanical Behaviour of In-situ Chondrocytes

Cartilage lesions change the microenvironment of cells and may accelerate cartilage degradation through catabolic responses in chondrocytes. In this study, we investigated the effects of structural integrity of extracellular matrix (ECM) on chondrocytes by comparing the mechanics of cells surrounded by an intact ECM with cells close to a cartilage lesion using experimental and numerical methods. Experimentally, 15% unconfined compression was applied to bovine cartilage tissues using a light-transmissible compression system. Target cells in the intact ECM or near lesions were imaged by dual-photon microscopy. Changes in cell morphology (n= 32 for both ECM conditions) were quantified. A two-scale (tissue level and cell level) Finite Element (FE) model was also developed. A 10% unconfined compression load was applied to a non-linear, biphasic tissue model with the corresponding cell level models studied at different radial locations from the center of the tissue in the transient phase and at steady state. Experimental and theoretical results indicated that cells near lesions deform less than chondrocytes in the intact ECM at steady state. Transient responses showed that cells near lesions experienced large (10 %) tensile strains in the direction of tissue thickness. Previous experiments showed that tensile strain causes an up-regulation of digestive enzyme gene expressions. Therefore, we propose that cartilage degradation near tissue lesions may be due to the tensile strains applied to cells, thus leading to an up-regulation of catabolic factors.