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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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Stress [Pa]<br />

4<br />

3<br />

2<br />

1<br />

0<br />

Mean stress<br />

Adhesion cell-bead = 20e-6 J/m 2<br />

Number of cells<br />

1<br />

0 20 40 60 80 100 120 140<br />

0<br />

Time [h]<br />

Figure 2: Average mechanical stress and total cell number vs time. Red: mean stress level ± 1 standard<br />

deviation. Black: Number of cells on microcarrier.<br />

4.2 Influence of microcarrier properties<br />

Commercial suppliers of microcarriers apply coatings to the beads in order to increase cellsubstrate<br />

adhesion, resulting in a higher cell yield after cell expansion cultures. We simulated<br />

cell expansion on spherical microbeads for five different values of cell-substrate adhesion Ka,cb in<br />

order to investigate their effect on the mechanical microenvironment. In Figure 3, the positions<br />

and stresses of the cells are shown for cell-bead adhesion values. Not only the spatial distribution<br />

and geometry of the cells, but also the magnitude of the compressive stress changes with Ka,cb.<br />

It should be pointed out that in the cases of very small Ka,cb, the cells won’t attach properly to<br />

the bead and will die or wash off in in vitro experiments. Both the mean compressive stress and<br />

spreading of stresses increase when Ka,cb becomes large (Figure 4a).<br />

(a) (b) (c) (d) (e)<br />

Figure 3: Simulated microcarrier cell expansion on microbeads with different cell-substrate adhesion values.<br />

(a): Ka,cb = 2.5e-6 J/m 2 , (b): Ka,cb = 5e-6 J/m 2 , (c): Ka,cb = 10e-6 J/m 2 , (d): Ka,cb = 20e-6<br />

J/m 2 , (e): Ka,cb = 40e-6 J/m 2<br />

Additionally, we performed simulations of cell expansion on microbeads for different Young’s<br />

moduli of the beads. The distribution of mechanical stresses on the cells is not as heavily influenced<br />

by the young’s modulus of the bead than its surface adhesion properties (Figure 4b).<br />

300<br />

250<br />

200<br />

150<br />

100<br />

50<br />

Number of cells

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