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International Journal of Bioprinting                                 Fluid mechanics of extrusion bioprinting




            approach explores the effect of nozzle geometry while   Given the widespread use of helical mixers in
            considering specific biomaterial properties, 176–178  and the   industrial applications, numerous numerical  simulations
            other investigates the dynamics of biomaterials for a fixed   are available in the literature that study the performance
            nozzle geometry. 179–181  Most studies have neglected cell-  of these mixers and the improvement of their geometry.
            biomaterial interactions and model the bioink as a single-  Numerical simulations of mixing two miscible biomaterials
            phase non-Newtonian fluid due to the low volume fraction   in an extrusion bioprinting head equipped with a helical
            of cells in bioinks. 63,182,183  However, several researchers have   mixer revealed an improvement in mixing efficiency as the
            utilized simulations to study cell deformation during the   power-law index of biomaterials increases. 192
            bioprinting procedure. 177,184                        Computational fluid dynamics (CFD) has been used
               Computational fluid  dynamics  (CFD)  simulations   to simulate the process forces or pressure work required
            have been used to predict the shear stress distribution in   for cell-damage predictions based on various cell damage
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            chamfered (straight) and tapered (conical) dispensing   models. Ning et  al.  and Han et  al.  employed CFD to
            nozzles, with results indicating a higher shear stress   provide information on the pressure drop and stress
            level inside chamfered nozzles compared to a tapered   distribution in the flow of alginate-based bioinks as they
            geometry. 185,186  The higher shear stress can lead to lower   are extruded through chamfered dispensing nozzles. They
            cell viability when using chamfered nozzles.  Most CFD   modeled bioinks, including alginate/RSC96 Schwann cells,
                                                88
                                                                                    63
            studies have focused on the flow through the dispensing   alginate/L8 myoblast cells,  and alginate/human dermal
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            nozzle and have explored the effects of printing pressure,   fibroblasts  cells,   using  the  power-law  non-Newtonian
                                                               model  in  their  numerical simulations  and analytical
            nozzle geometry, and rheological properties of bioinks on   calculations. Chirianni et al.  used CFD to validate their
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            the shear stress exerted on the cells in the bioink. 63,182,183
            The distribution of wall shear stress for different nozzle   cell-damage model with previous experimental test results.
                                                               They modeled bioinks based on alginate-based human
            geometries suggests that optimizing nozzle geometry   dermal fibroblasts as a Carreau-Yasuda non-Newtonian
            involves balancing printing resolution and cell viability.   fluid in their numerical simulations. Their numerical
            The nozzles featuring a smaller convergence angle tend   results for the distribution of shear and extensional stresses
            to produce higher wall shear stress (Figure  14A–C),   magnitude inside the nozzle are displayed in Figure 14D
            potentially leading to adverse effects on cell viability. 187,188  and E. This figure illustrates how extensional stress peaks
               Numerical simulations have also been employed   in the contraction region of the nozzle.
            to  model  the  flow  of bioinks  inside coaxial  dispensing   Chávez-Madero et  al.  and Ceballos-González
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            systems. These simulations have been used to understand   et  al.169 used CFD simulation and massless particle
            the parameters controlling the diameter, velocity, and mass   tracking methods to predict the thickness and patterns
            of the gel fiber near the nozzle outlet during the extrusion   of the internal multi-layer structures generated by a
            of hollow strands, 189,190  using biomaterials such as alginate   helical mixer. The results were in good agreement with
            with a crosslinker.                                experimental visualization and the theoretical average
               In cases  where extrusion involves mixing two or   thickness of the internal layers (Figure 13B–D).
            more biomaterials, and assuming the effect of cells in the   Computational fluid dynamics (CFD) simulations play
            flow of bioinks is negligible, the mixing of bioinks can   a crucial role in microfluidic studies by providing data
            be simulated by solving of the components’ transport   about the distribution of velocity, pressure, concentrations,
            equations (excluding considerations of chemical reactions   and shear stress, which can be challenging to measure
            and phase changes). 191                            experimentally. Several computational simulations have
                                                               been conducted by researchers to investigate the effects of
                       D ρ (  Y )                             shear stress on cell viability and explore the flow of various
                            i
                         Dt   =− ∇⋅  J i           (XXXIX)     biomaterials inside customized nozzle geometries. 178,193
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                                                                  Zaeri et al.  studied the flow in a coaxial microfluidic
               where                                           bioprinting chip numerically, where CFD was used to
                                                              study the effect of printing parameters on the geometrical
                         J i =−ρ D im ∇ Y i           (XL)     outcome of the printed fiber. Their simulation did not
                                ,
                                                               consider the deposition of fiber on the printing stage;
               and Y is mass fraction of component i; and D  is its   instead, the structure of the fiber was investigated based on
                   i
                                                    i,m
            diffusion coefficient.                             the flow structure at the nozzle outlet cross-section. They

            Volume 10 Issue 6 (2024)                       140                                doi: 10.36922/ijb.3973
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