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ARUP; ISBN: 978-0-9562121-5-3 - CMBBE 2012 - Cardiff University

ARUP; ISBN: 978-0-9562121-5-3 - CMBBE 2012 - Cardiff University

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configuration. During random placement, a minimum pericellular-to-pericellular<br />

spacing of 2.5 μm and a minimum pericellular-to-tissue-edge spacing of 1.25 μm were<br />

enforced. The cells have radii of 5 μm, surrounded by a layer of pericellular matrix with<br />

a thickness of 2.5 μm [4]. A biphasic constitutive model was utilized, with a nonlinear<br />

elastic (Neo-Hookean) solid component and the fluid component modeled with Darcy's<br />

Law with strain invariant permeability [9], and with properties adopted from [4] for the<br />

middle zone cartilage depth. The extracellular matrix had a Young's modulus of 0.15<br />

MPa, a Poisson's ratio of 0.4, and a hydraulic permeability of 0.002 mm 2 /N-s. For the<br />

pericellular matrix these were 0.043 MPa, 0.04, and 0.002 mm 2 /N-s; for the cell(s),<br />

0.0034 MPa, 0.4, and 0.001 mm 2 /N-s. The larger block, in which the single cell and<br />

eleven cell RVEs were embedded, was given the same properties as the ECM.<br />

The interface between the RVE and the larger block contained hexahedral transition<br />

elements which allowed the larger volume to contain larger elements in order to reduce<br />

the total number of elements in the model, while allowing for node-to-node merging of<br />

the two meshes, eliminating the need for enforcement of any coupling constraint. The<br />

embedded models contained 148,368 and 152,868 elements for single cell and eleven<br />

cell cases, respectively. In the tissue-scale region of the models the approximate average<br />

element edge length was 3 μm, while the elements in the embedded RVEs had edge<br />

lengths of approximately 0.2 μm. A mesh convergence study was not conducted for the<br />

multi-scale construct models as these were near the upper bound of shared memory<br />

architecture computational resources available. However, a mesh convergence study<br />

was conducted on the RVE models. Models of lower mesh density than those employed<br />

in this were shown to converge in 3 rd principal stress, strain, and total fluid flux for both<br />

the single and 11 cell cases. Due to the need to satisfy strict element density ratios at the<br />

transition interfaces, the converged meshes had there element densities further refined,<br />

but since the meshes were of higher density these were also assumed to be converged.<br />

The whole construct was subjected to 10% compressive strain (ramped over 0.1 seconds<br />

and held for 9.9 seconds) with confined boundary conditions (zero expansion of or fluid<br />

flux over the lateral faces). The top and bottom faces of the outer tissue blocks were<br />

Figure 2. (a) Volume averaged effective strain for individual cells as a function of<br />

time. Cut-away views of the RVE for the (b) eleven and (c) single cell models<br />

highlight the strain state within a given cell at the end of the simulation. Arrows<br />

correlate the particular cells in the contour plots (b and c) with the corresponding cell<br />

number in (a) .

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