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International Journal of Bioprinting                        CFD analysis for multimaterial bioprinting conditions



            The most commonly used additive manufacturing (3D   rapidly expanding field to overcome the restrictions of
            printing) techniques [5,6]  to create cell-laden constructs   mixing highly viscous biomaterials .
                                                                                           [25]
            are material jetting [7,8] , extrusion-based [2,9] , and light-  Computational fluids  dynamics  (CFD),  simulations
            based technologies [10,11] . Multimodal systems, integrating   of the biopolymer flow in extrusion-based bioprinting
            different  printing  principles  into  a  single  machine,  have   processes, are widely used to understand the relationship
            been also proposed . Among these printing strategies,   between printing parameters, nozzle size and geometry,
                            [6]
            extrusion-based bioprinting is one of the most commonly   viscous forces, and material properties during the
            used  approach  as  it  allows  to  print  materials  with  a   bioprinting process. More specifically, it enables to
            wide range of viscosities and to fabricate multimaterial/  determine inner parameters that are experimentally
            cellular volumetric biological constructs [12-14] . In extrusion   difficult to evaluate, such as pressure, velocity, flow rate,
            bioprinting, biocompatible cell-laden hydrogels are   and also shear stresses on cells in the case of bioinks. It
            loaded  into  the  cartridges  (reservoirs)  and  deposited  on   is  known  that  the  dispensing  pressure,  and  particularly
            a bioprinting platform using one or several nozzles via   shear stresses, have a significant influence on cell
            pneumatic, mechanical, or solenoid actuation .     survival [26-29] . However, only few simulation studies have
                                                [5]
               A key object of tissue engineering applications is the   investigated shear stresses and cell viability on extrusion-
            fabrication of multimaterial and multiscale heterogeneous   based bioprinting processes, considering different nozzle
            constructs, mimicking the organized cellular architecture   geometries and dispensing pressures [30-34] . Moreover, all
            and functionality of natural tissues . However, this is not   these studies have only considered the simulation of a
                                        [15]
            achievable  with single-material bioprinting approaches,   single-material bioprinting process.
            as they often fail to replicate the complexity and variety   In this work, we extensively investigated the extrusion
            of real tissues consisting of multiple layers of different cell   process of non-Newtonian alginate and gelatin solutions,
            types . To overcome this shortcoming, multimaterial   through an entire and novel dispensing system consisting
                [16]
            bioprinting emerged as a promising approach [6,15-17] .   of two cartridges, KSM integrated mixing chamber and
            Multimaterial 3D bioprinting technique refers to the   a single nozzle. To the best of our knowledge, to date, no
            simultaneous  or  sequential  deposition  of  two  or  more   numerical study has yet investigated the inner parameters
            biomaterials in a predetermined manner to create region-  such as shear stress, pressure, and velocity field as well
            specific characteristics and performances . These type   as mixing index within the KSM-embedded 3D model
                                              [16]
            of heterogeneous bioconstructs have been fabricated   of printing head flow domain. The spatial distribution
            using multireservoir and multinozzle printing systems .   of the two different polymer solutions was quantitatively
                                                        [18]
            However, the fundamental limitation of these multinozzle   characterized by determining the mixing index. To
            bioprinting systems is the considerably long printing time   understand the effect of the printing needle geometry on
            while switching between different bioinks, in addition to   the inner parameters, cylindrical and conical nozzles with
            the need of accurate calibration of all printheads before   varying outlet diameters were investigated considering
            the  deposition  process [3,19,20] .  Moreover,  multinozzle   different printing pressures. The simulation results were
            bioprinting systems result in a discontinuity in the printed   validated by comparing predicted pressure drop results
            filament morphology that adversely affect the mechanical   at different Reynolds numbers with existing empirical
            integrity of the 3D-printed structures . To overcome these   correlations. This model can be easily adapted to different
                                         [19]
            limitations, several researchers focused on bioprinting of   biomaterials.
            multiple hydrogels through a single nozzle [20-23] .
               Implementing multireservoir single-nozzle systems is   2. Materials and methods
            simple, though this strategy is ineffective for systematically
            printing tissue engineering structures with continuous   2.1. Computational fluid dynamics analysis
            gradient features. A variety of mixers have been used to   A computational fluid dynamics (CFD) analysis was
            tackle this limitation by blending two or more biomaterials   performed by using the simulation software package
            in various concentrations to facilitate multimaterial   ANSYS® Academic Research Fluent 19.2 (ANSYS,
            bioprinting tasks . In this case, active and passive or   Canonsburg, PA, USA) to numerically evaluate the mixing
                          [23]
            static mixers have been extensively studied. Static mixers   mechanism of two different biomaterials through a static
            are  usually  easier  to  assemble  and  more  biocompatible   mixer integrated printing head, and both the velocity and
            compared to active mixers, since they cause less shear   shear stress distribution profiles at the needle outlet during
            stresses to the encapsulated cells . Recently, Kenics static   the extrusion process. Figure 1 shows the computer-aided
                                      [24]
            mixers (KSM) have been employed to enable chaotic   design (CAD) model of the printing head equipped with
            bioprinting of multimaterial constructs  and this is a   cartridges, static mixer, and a cylindrical or a conical
                                            [15]

            Volume 9 Issue 6 (2023)                         12                        https://doi.org/10.36922/ijb.0219
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