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Computational studies of chondrocyte mechanics, and cell mechanics in general, have typically been performed using single cell models embedded in an extracellular matrix construct. The assumption of a single cell microstructural model may not capture intercellular interactions or accurately reflect the macroscale mechanics of cartilage when higher cell concentrations are considered, as may be the case in many instances. Hence, the goal of this study was to compare cell-level response of single and eleven cell biphasic finite element models, where the latter provided an anatomically based cellular distribution representative of the actual number of cells for a commonly used [Formula: see text] edge cubic representative volume in the middle zone of cartilage. Single cell representations incorporated a centered single cell model and eleven location-corrected single cell models, the latter to delineate the role of cell placement in the representative volume element. A stress relaxation test at 10% compressive strain was adopted for all simulations. During transient response, volume- averaged chondrocyte mechanics demonstrated marked differences (up to 60% and typically greater than 10%) for the centered single versus the eleven cell models, yet steady-state loading was similar. Cell location played a marked role, due to inhomogeneity of the displacement and fluid pressure fields at the macroscopic scale. When the single cell representation was corrected for cell location, the transient response was consistent, while steady-state differences on the order of 1-4% were realized, which may be attributed to intercellular mechanical interactions. Anatomical representations of the superficial and deep zones, where cells reside in close proximity, may exhibit greater intercellular interactions, but these have yet to be explored.

The potential for intercellular mechanical interaction: simulations of single chondrocyte versus anatomically based distribution