Finite element analysis of single cells embedded in an extracellular matrix have been used widely to provide new insights into the cellular loading in cartilage [1] and meniscus [2]. Deformations derived from a homogeneous tissue model are generally used to drive simulations using microstructural representations. Implicit in this setup is the assumption of the equivalence of macrostructural (tissue) constitutive response and average stress-strain response of the microstructural (cellular) model. Higher cell densities within tissue volume [3] may increase the uncertainty introduced by this assumption and may also influence how macroscopic loads are transferred to the cells. We have previously shown, albeit with a two-dimensional simulation, the potential mismatches in such variables for increasing strain level and cell density, specifically for no cell, one, and three cell representations [4]. Hence, the objective of this study was to quantify the differences between the overall response and cellular deformation in three-dimensional nonlinearly elastic microstructural cartilage models embedded with either one or three cells. Multiscale coupling approaches targeting prediction of cell deformations from tissue and/or organ level loading will likely benefit from this investigation while balancing computational demand with accuracy requirements.

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