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International Journal of Bioprinting                                 Fluid mechanics of extrusion bioprinting




            and  cell-containing  solutions,  followed  by  their   the nozzles and accurate control of the bioink flow are
            simultaneous deposition. For example, coaxial printing   necessary when changing printing heads to maintain
            involves minimal contact between precursors as they exit   structural integrity.  To address the slow printing
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            the nozzle and to deposit on the printing stage, where   issue, some bioprinters incorporate multiple arms with
            crosslinking solidifies them. Other methods, like the head   independent motion paths and heads.  However, this
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            sweeping technique, deposit different bioinks separately.   approach introduces challenges in aligning the arms
            In contrast, multi-material bioprinting with mixing, such   accurately, which can potentially impact the overall
            as using micromixer-equipped heads, involves contact   integrity of the printed scaffolds. 131
            between precursors before deposition. Depending on
            the design and application, the extent of mixing can vary   4.1.2. Coaxial printing
            from minimal (separated) to homogeneous. Most of   Coaxial  printing  is  an  emerging  technique  in  extrusion
            these methods are designed to maximize the mixing of   multi-material bioprinting 132–136  that uses coaxial needles
            precursor biomaterials and cells, enabling the deposition   for printing core–shell fibers. This method involves
            of a homogeneous mixture with precise control over   inserting small-diameter needles into larger-diameter
            composition during the printing process.
                                                               needles, allowing for the fabrication of structures with
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            4.1. Extrusion multi-material bioprinting          core–shell or hollow fibers.  Depending on the specific
            without mixing                                     application, different biomaterials and cell types can be
                                                               extruded as the core or sheath layer of the filament. 11
            4.1.1. Swapping the dispensing heads
            The simplest approach for multi-material bioprinting   Coaxial  bioprinting  can  significantly  improve  the
            is swapping the dispensing heads on the bioprinter.   mechanical  properties  of  biomaterials  by  combining
            This method enables hierarchical printing of different   them with stronger biomaterials. For example, core–shell
            bioinks   62,125–127  by loading different biomaterials onto   polyethylene glycol diacrylate (PEGDA)/alginate filaments,
            separate printing heads, which are sequentially mounted   with alginate as the core and PEGDA as the shell, exhibit
            on the printing arm. This allows for specific parts of   higher tensile moduli and strengths compared to alginate.
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            the scaffold to be printed in a predetermined manner.   This method allows for printing a cell-laden hydrogel as
            Hydrogels are typically pre-mixed with cells and facilitate   the core, while the shell provides structural integrity and
            the  simultaneous  printing  of  multiple  bioinks.   For   protection for the cell-laden hydrogel.  Furthermore,
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            example, a multi-head system can be utilized to print   coaxial printing enables the creation of advanced scaffold
            cell-laden scaffolds using decellularized extracellular                             28,138
            matrix  (dECM)-based bioink  and polycaprolactone   structures, including vessel-like channels.   However, a
            (PCL).  This method has also proven successful in   major challenge in coaxial printing is the difficulty in using
                 128
            creating hybrid scaffolds that combine alginate and PCL,   multiple coaxially assembled needles to produce small-
            exhibiting improved mechanical properties compared to   diameter fibers, due to the requirement of larger-diameter
            pure alginate scaffolds. 125,129  However, this method can   outer needles to accommodate the internal small-diameter
            only print one bioink at a time, resulting in a relatively   needles.  Despite this, coaxial heads can print fibers with a
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            slow printing process. Additionally, precise alignment of   core–shell structure without mixing the materials.


            Table 4. Rheological characteristics and models for common biomaterials

            Biomaterials             Newtonian/non-Newtonian                        Models             Ref.
            Alginate                 Non-Newtonian: (i) shear-thinning; (ii) thixotropy; (iii)   Power-law; cross; viscoelastic   112–116
                                     viscoelastic                                    (PTT)
            Alginate/gelatine        Non-Newtonian: (i) shear-thinning; (ii) viscoelastic  Herschel-Bulkley  117
            Agarose                  Non-Newtonian: (i) shear-thinning; (ii) viscoelastic  Power-law   118
            Carboxymethyl cellulose (CMC)  Non-Newtonian: (i) shear-thinning; (ii) thixotropy; (iii)   Power-law; cross  119
                                     viscoelastic
            Chitosan                 Non-Newtonian: (i) shear-thinning; (ii) thixotropy; (iii)   Carreau-Yasuda  120,121
                                     viscoelastic
            Collagen                 Non-Newtonian: (i) shear-thinning; (ii) viscoelastic  Power-law; Carreau  122
            Gelatin                  Non-Newtonian: (i) shear-thinning; (ii) viscoelastic  Power-law   123,124

            Volume 10 Issue 6 (2024)                       132                                doi: 10.36922/ijb.3973
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