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International Journal of Bioprinting A computational model of cell viability and proliferation of 3D-bioprinted constructs
Figure 6. Spatial distribution of the investigated variables (I: oxygen; II: glucose; and III: cell density) within the four different models of bioprinted
specimens (A: 1X; B: 2X; C: 3X; and D: 3X with channels).
can be adapted to complex 3D geometries, differently from applying the boundary conditions at the interface with the
existing works that already implement these features but solid construct.
are simplified to one preferential direction; for instance, We hereby discuss some limitations of the current
Higuera et al. applied the study to a 2D culture, or model. The cell-embedded hydrogel matrix was modeled
[20]
Xu et al. developed a realistic model of diffusion and as a continuum and the diffusivity coefficient was taken
[21]
consumption that can be applied to 3D bioprinting, but from the literature. Yet, the effects of crosslinking where
neglected three-dimensionality of the phenomena and not included in the model. Experimental studies will be
solved it analytically. In the context of 3D bioprinting, needed to provide a deeper insight into the effects of the
which allows for freedom in the design to create complex crosslinking degree on nutrient diffusivity, which can be
shapes and is intended to be used for the manufacturing implemented easily in the model through the diffusivity
of 3D tissues and organs, it is of great importance to coefficient. Possible interactions of nutrients with the
analyze the spatial variations in the whole 3D geometry. proteins of the hydrogel would also need attention and
The model is intended to be applied to constructs of any would require additional terms in the equations.
material, size, and geometry, as far as the hypothesis of
continuum mechanics holds. Once the most appropriate A preliminary validation of the volume-averaged
parameter values are set, as supported by the sensitivity model, yielding a system of ordinary differential equations,
analysis, the model can be used to simulate different was carried out. For this purpose, an experimental test of
scenarios and to realize predictions. The computational extrusion bioprinting and viability assessment was carried
domain allows for modeling complex geometries, making out. A basic model of 3D constructs was chosen for extrusion
it suitable to study diverse and multiscale features that bioprinting of cells embedded into a bioink, which resulted
are typical of biological tissues obtained through 3D in droplet-shaped constructs. This basic geometry allows
bioprinting. In particular, the introduction of channels is for easy inspection and analysis yet constitutes a model of
of particular interest, and it can be implemented in the bioprinted construct. Although the vertical dimension is
model by changing the geometry of the domain and by small, cells are embedded in a hydrogel matrix; therefore,
Volume 9 Issue 4 (2023) 362 https://doi.org/10.18063/ijb.741

