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16.6 SOME APPLICATIONS OF INTEREST 335

×10 6
18
S: Alive
S: Dead
16
Experimental
14
Cell concentration [c/mL] 10 8
12

4 6

2
0
0 0.05 0.1 0.15 0.2 0.25
Length [µm]
FIG. 16.8 Cell culture at 3 days.

species in the general framework, such as temozolomide (TMZ) or other drugs, may be used in order to evaluate the
effect on GBM tissue evolution and to explore many other chemotherapy strategies.
Nevertheless, there are still many obstacles to overcome. First, there is an obvious need for a better characterization
of boundary and initial conditions of the experiments. Cell leakage and oxygen supply as well as the initial oxygen
profile have important impacts on cell evolution and therefore in parameter calibration. In the present work, boundary
and initial conditions have been established in a reasonable manner, obtaining a good accordance between predicted
and observed results but a perfect characterization is desirable.
Moreover, in order to make predictions, it is important to consider intercell culture parameter variability. As is usual
in biological research, it is difficult to obtain a universal model able to reproduce GBM. With respect to applications, it
is desirable to obtain patient-specific models, that is, parameters and geometries, for the simulations.
Finally, there is a lot of room in the short-term reaction of the cell for physiological stimuli. The presented model is
able to capture long-term cell evolution features when genetic cell damage has already occurred. There is, however, the
necessity of a better understanding of cell damage in the short term when the cell has not yet adapted its metabolism to
new microenvironment conditions. How long does it take for a cell to become migratory? Is it instantaneous? Exper-
iments demonstrate that it is not, but the mathematical model does not include this kind of feature, as is shown in
Fig. 16.8, where we can conclude that the presented mathematical model underestimates cell proliferation in the
first week.

16.6.2 In Silico Design and Quantification of Experiments in Microfluidic Devices
Three-dimensional simulations may be used in chip design and fabrication and in experiment set up. When a cell
culture is going to be seeded on a chip, the objective is to reproduce, in the microfluidic device, the desired tumoral
microenvironment, that is, the appropriate mechanical properties, nutrient and oxygen supplies, and gradients. The
goal is to design properly the experiment in order to make suitable conclusions in a reasonable time. For that, it is
necessary to define precise device geometry and boundary conditions so that cell cultures are subjected to the desired
chemical and mechanical stimuli.
In order to illustrate all this, a simulation in a 3D chip-like geometry is going to be presented for a very fundamental
model. Two cell phenotypes are going to be considered, alive and dead cells, C n and C d , respectively, and the oxygen
O 2 is going to be the driving chemoattractant.

II. MECHANOBIOLOGY AND TISSUE REGENERATION