ORGAN PRINTING - 3D Bioprinting and Nanotechnology in Tissue Engineering and Regenerative Medicine - page 332

FIGURE 15.2
Identification of three distinct regimes of the printed micro-organ based on average cell WSS and maximum WSS at
the single-cell level.
experience higher VM stresses than the middle cells as shown in Figure 15.3 . This can be explained by
the fact that the VM stress represents the sum of both the normal and shear stresses. Thus, it is evident
that the entrance cells experience higher normal stresses compared to the middle cells, which are in
contact and in parallel with the fully developed laminar velocity profile of the shear-induced flow field.
However, for the assessment of the dynamic micro-organ device, cell WSS metrics are used, since
available literature data for optimum hepatocyte function in dynamic cell cultures is given in terms of
WSS. It is reported by Tanaka et al. ( Tanaka et al., 2006 ) that hepatocytes tend to alter their cellular
morphology and metabolite function under various conditions of shear-mediated flow in a microchip.
In particular, their metabolic activities in terms of albumin synthesis are decreased under shear stresses
higher than 2 Pa, increased in the range of 0.14 Pa to 1 Pa and remained relatively constant from 1 to
2 Pa. Moreover, Kan et al. ( Kan et al., 1998 ) tested the shear stress effect on the metabolic function of
a coculture system of hepatocytes/parenchymal cells and reported a shear stress value of 0.47 Pa for
optimum conditions.
The fact that these reported values are one to two orders of magnitude larger compared to the cell
WSS obtained for the dynamic micro-organ device system compelled the authors to vary the magni-
tude of the inlet volumetric flow rate within the model environment to achieve cell WSS on the same
order of magnitude with the results depicted in Figure 15.4 . Specifying one cell from each regime of
the bioprinted tissue shows that the comparatively low inlet volumetric low rate in the postprocessing
phase needs to be increased 10-20 times from the initial value of 0.25 m l/h in order for the flow field to
induce cell WSS for optimal hepatocyte function.