Quantification of Cartilage Poroelastic Material Properties via Analysis of Loading-Induced Cell Death.

To facilitate smooth and pain-free joint motion, articular cartilage (AC) relies on the health of its resident cells (chondrocytes). However, the factors governing the vulnerability of chondrocytes to mechanically-induced death or injury are not fully understood. Thus, the objective of this study was to determine whether tissue deformation or load magnitude drives chondrocyte death under sub-impact (negligible kinetic energy) loading conditions. We hypothesized that there is a critical tissue deformation at which chondrocytes are killed. To test this hypothesis, murine cartilage-on-bone explants from different anatomical locations were subjected to constant or dynamic loading conditions in a custom device. Parallel simulations were performed using finite element modeling. For constant loading conditions, due to poroelastic creep, deformation increased over time. Thus, the isolated effects of deformation (independent of load) were assessed by quantifying cell death as a function of loading duration. We found that cell death area increased with loading duration - and, in turn, with tissue deformation - for constant loading conditions. Similarly, we found that both tissue deformation and cell death area were reduced in dynamic loading conditions as compared with static loading conditions. Collectively, these data suggest that mechanically-induced chondrocyte death is driven by tissue deformation, not load. As a practical application of these findings, we used the relationship between cell death and tissue deformation to devise and validate an inverse finite element modeling procedure enabling calculation of poroelastic material properties based solely on time-dependent cell death measurements under constant loading conditions.