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International Journal of Bioprinting                                 Fluid mechanics of extrusion bioprinting




            level of mixing. These microfluidic systems draw different   complexity. Idaszek et  al.  introduced an innovative
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            biomaterials from separate reservoirs and extrude   coaxial 3D extrusion bioprinting system that incorporated
            them as a single multi-material fiber, ensuring precise   a microfluidic mixing unit to fabricate 3D constructs with
            control over the concentration of precursor biomaterials   gradients of cells and biomaterials, specifically designed for
            at  the outlet. 143,170   Colosi   utilized  a  simple  Y-shaped   chondral defect repair. This platform enabled the separate
                                 171
            microfluidic chip with coaxial outlet to print a cell-laden   delivery of various bioinks or their quick mixing within
            heterogeneous  construct  composed  of  core–shell  fibers.   the microfluidic mixer prior to extrusion through a coaxial
            Microfluidic systems are among the fastest methods for   nozzle. The system facilitated the generation of gradients
            bioprinting. However, due to the single-nozzle design, these   in composition, mechanical properties, and biological
            systems can only print one bioink or a mixture of bioinks   cues, resulting in constructs with high structural integrity
            at a time.  While designs with co-flow of biomaterials   and enhanced bioactivity.
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            inside a Y-microchannel (Figure 10A) promotes mixing,
            designs equipped with micromixer elements (Figure 10C   5. Numerical simulation of bioprinting
            and  D) effectively facilitate the mixing of biomaterials
            during the extrusion process. Although both active and   Due to the high cost of most cell-containing bioinks and the
            passive micromixers can work in microfluidic printing   time-consuming nature of bioprinting tasks, researchers
            systems, passive micromixers are more popular due to   have increasingly turned to computational fluid dynamics
            their simplicity and relatively mild effect on cells. Passive   (CFD) simulations as a valuable complementary approach.
            micromixers operate based on interdigitation mechanism,   These  simulations  analyze the  extrusion,  mixing,  and
            which can be achieved through split-and-recombine (SAR)   deposition processes involved in bioprinting by leveraging
            flow guidance methods or chaotic mixing. 160       the detailed information from the numerical solutions of
                                                               the governing equations. 88
               Strook et  al.  demonstrated that a grooved-wall
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            micromixer can benefit from chaotic advection to      Numerical simulations of bioprinting processes allow
            decrease the mixing distance. They reported that for   for a deeper understanding of the relationships between
            grooved-wall micromixers,                          nozzle geometry, bioink properties, printing parameters,
                                                               and extrusion forces. These simulations play a crucial
                                                               role in predicting the impact of the printing process on

                            lnPe <                  (XXXV)     cell  viability  and  the  shape  of  the  extruded  fiber.  CFD
                                  d                           techniques have  the potential  to optimize  dispenser
               which shortens the length of mixing channel required   geometry, printing conditions, and even facilitate the
            for complete mixing of precursors.                 development of  new  bioink compositions,  reducing  the
                                                               need for extensive experimental testing. 63,174
               Angelozzi et  al.  demonstrated that adding a
                             152
            serpentine micromixer to the Y-shaped microfluidic chip   In order to model the flow of bioinks during the extrusion
            (Figure  10D) enhances the mixing of osteoblast cells   bioprinting process, the governing equations of fluid flow,
            within the alginate solution and facilitates the deposition   along with appropriate boundary conditions, should be
            of fibers with homogeneous distribution of cells. The   solved numerically using commonly employed methods,
            serpentine micromixer  can facilitate the  chaotic mixing   such as finite-volume or finite-element approaches.
            process by generating Dean vortices in the flow cross-  The numerical solution method enables researchers to
            section. The straight channels (Figure 10A) were found to   simulate and analyze the intricate fluid dynamics within
            cause cell segregation along one side of the printed fibers   the bioprinting system, providing valuable insights into the
            due to the laminar dispersion of cells in the flow inside the   behavior of bioinks and their interaction with the printing
            microfluidic device. 148,152                       environment. By leveraging these simulations, researchers
               Based on the intended purpose and the desired   can make informed decisions regarding printing
            structure of the printed scaffold, a microfluidic chip   parameters, biomaterial compositions, and optimization
            with a specialized function can be custom-designed and   strategies, ultimately advancing the capabilities of
            integrated into the printing head. For instance, combining   bioprinting technology. 63
            microfluidic chips with coaxial printing heads can harness
            the advantages of  both approaches  for bioprinting.  The   Assuming laminar, incompressible flow, the governing
            integration of the microfluidic chip upstream of the   equations for the flow of biomaterials can be written
                                                               as follows:
            coaxial dispensing nozzle enables the printing of low-
            viscosity  bioinks  while  attaining  high  architectural   (i)  Continuity :
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            Volume 10 Issue 6 (2024)                       137                                doi: 10.36922/ijb.3973
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