Page 318 - Advances in Biomechanics and Tissue Regeneration

316 16. ON THE SIMULATION OF ORGAN-ON-CHIP CELL PROCESSES

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FIG. 16.2 Pseudopalisade formation. U-251 at 4 10 cells/mL in collagen hydrogel were cultured within microdevices. Under unrestricted con-
ditions, the medium was refreshed once a day. To mimic obstructed conditions, the medium flow was enabled only through the right microchannel.
(A)Cellviabilitywasevaluatedafter3,6,and9daysusingcalcein(green)andpropidiumiodide(red).Graphsshowthefluorescenceintensityacrossthe
microchamber orthogonal view at 3, 6, and 9 days in obstructed and unrestricted conditions. (B) Oxygen profile was detected after 5 days in culture
using Image-it Hypoxia reagent. Images are shown as heat-map hypoxia-induced fluorescence intensity. Hypoxia-induced fluorescence intensity
across the microchamber revealed that the oxygen concentration was constant under unrestricted conditions, whereas an oxygen gradient was estab-
lished under obstructed conditions. The graph shows the hypoxia-induced fluorescence intensity profile across the microchamber [39].

In the experiment that we shall simulate with our mathematical framework, we follow a slightly different approach.
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The same concentration of cells (4 10 cells/mL) was seeded within the central chamber, but now the growth
medium was perfused through both lateral microchannels, simulating two functional blood vessels. We wanted to
see if we were able to maintain cell culture long enough to spontaneously create hypoxic conditions in the center
of the chamber and induce cell migration and invasion of both lateral channels, that way mimicking double pseudo-
palisade formation.

II. MECHANOBIOLOGY AND TISSUE REGENERATION