Superficial zone chondrocytes can get compacted under physiological loading: A multiscale finite element analysis

Recent in vivo and in vitro studies have demonstrated that superficial zone (SZ) chondrocytes within articular layers of diarthrodial joints die under normal physiologic loading conditions. In order to further explore the implications of this observation in future investigations, we first needed to understand the mechanical environment of SZ chondrocytes that might cause them to die under physiological sliding contact conditions. In this study we performed a multiscale finite element analysis of articular contact to track the temporal evolution of a SZ chondrocyte's interstitial fluid pressure, hydraulic permeability, and volume under physiologic loading conditions. The effect of the pericellular matrix modulus and permeability was parametrically investigated. Results showed that SZ chondrocytes can lose ninety percent of their intracellular fluid after several hours of intermittent or continuous contact loading, resulting in a reduction of intracellular hydraulic permeability by more than three orders of magnitude. These findings are consistent with loss of cell viability due to the impediment of cellular metabolic pathways induced by the loss of fluid. They suggest that there is a simple mechanical explanation for the vulnerability of SZ chondrocytes to sustained physiological loading conditions. Future studies will focus on validating these specific findings experimentally. As with any mechanical system, normal ‘wear and tear’ of cartilage tissue lining joints is expected. Yet incidences of osteoarthritis are uncommon in individuals younger than 45. This counter-intuitive observation suggests there must be an intrinsic repair mechanism compensating for this wear and tear over many decades of life. Recent experimental studies have shown superficial zone chondrocytes die under physiologic loading conditions, suggesting that this repair mechanism may involve cell replenishment. To better understand the mechanical environment of these cells, we performed a multiscale computational analysis of articular contact under loading. Results indicated that normal activities like walking or standing can induce significant loss of intracellular fluid volume, potentially hindering metabolic activity and fluid transport properties, and causing cell death. [Display omitted]