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

                                      1.0e+06
                                      950,000
                                      900,000
                                      850,000
                                           P1
                                      800,000
                                      750,000

                                      6.9e+05
                                  (A)







                                      1.0e+06
                                      950,000
                                      900,000
                                      850,000
                                      800,000
                                           P1
                                      750,000
                                      6.9e+05
                                  (B)








                                      1.0e+06
                                       950,000
                                       900,000
                                      850,000
                                           P1
                                       800,000
                                       750,000
                                       6.9e+05

                                  (C)
           FIG. 16.11  Evolution of alive cells in the culture chamber (in cell/mL). (A) t ¼ 0 s; (B) t ¼ 42 h; (C) t ¼ 70 h.


                                                  16.7 CONCLUSIONS

              The combination of organ-on-chip devices and computational models is a perfect option to set up new complex
           biological models that include diffusion, advection, chemotaxis, mechanotaxis, electrotaxis, thermotaxis, proliferation,
           differentiation, and cell death as well as the interaction of the different cellular phenotypes with chemical species (such
           as nutrients or chemical cues) and ECM remodeling. Experimental campaigns are needed in order to define and cal-
           ibrate proper mathematical models, but promising results have been obtained in the study of in vitro GBM models.
              The main contribution of this work is the presentation of a framework integrating in vitro experiments in 3D bio-
           mimetic platforms, able to capture the enormous complexity of tumoral microenvironment biophysics, with in silico
           simulation models, which serve to extrapolate the conclusions to different pictures and to help the researcher in new
           hypotheses formulations and experimental campaign designs. Microfluidic devices offer flexible and realistic exper-
           imentation. The presented mathematical model is rich enough to capture all TME physics with a variable degree of
           complexity.


                                          II. MECHANOBIOLOGY AND TISSUE REGENERATION
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