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International Journal of Bioprinting                              Bioprinted organ-on-a-chip with biomaterials




            structure containing cells—has found widespread use   2.2.2. Inkjet bioprinting
            across various fields of bioengineering. This method has   Inkjet bioprinting system is a non-contact technique that
            been developed using a range of engineering techniques.    delivers controlled droplets of cells or biomaterials using
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            Among  the  most  used  3D  bioprinting  technologies  are   various  methods,  including  electrically  heated  bubbles,
            inkjet, extrusion-based, and laser-assisted bioprinting.   valve-controlled pressure pulses, and piezoelectric
            Each of these technologies is classified based on the method   actuators  (Figure 2B).
                                                                      79
            of releasing cells and biomaterials, and each method comes   The printhead of a thermal inkjet printer is electrically
            with its distinct advantages and disadvantages.  The   heated to create a pressure pulse that pushes the droplet
                                                     74
            following is a brief description of these technologies, and   out of the nozzle. The maximum heating temperature of a
            Table 2 provides a summary of 3D bioprinting methods   thermal printer is as high as 300°C; however, the duration
            along with bioink requirements.
                                                               is relatively short, so it does not adversely affect cell survival
            2.2.1. Extrusion-based bioprinting                 or biomaterial denaturation. Thermal inkjet printing offers
            An extrusion-based bioprinting system applies specific   advantages  such  as  low cost and  high  printing speed.
            pressure to the syringe nozzle, depositing viscous   However, it does have limitations in controlling the size or
            biomaterial to form a continuous liquid bead (Figure   direction of the droplets. Additionally, mechanical stress
            2A). As  the  extrusion head  or stage moves  along  the   on the cells and frequent nozzle clogging are encountered. 80
            z-axis, the next layer is sequentially stacked on top of   A valve-controlled pressure pulse inkjet printer
            the previously deposited layer, resulting in the creation   applies a specific pressure and controlled pulsed voltage
            of a 3D biological structure. Control over the amount   to the liquid in the printhead and then opens and closes
            of extruded biomaterial is achieved by adjusting the   the electromechanical valve to form droplets. Compared
            pneumatic or mechanical pressure, nozzle size, or nozzle   with other inkjet printing methods, this approach has
            speed along the x- or y-axis. 23,75,76  The composition of an   the advantage of enhanced cell deposition and viability
            extrusion-based bioprinting system is relatively simple   because it does not use heat. 81
            compared with other bioprinting systems, rendering it
            a cost-effective option. Extrusion-based bioprinting is   A piezoelectric inkjet printer has a piezoelectric
            a commonly used method for fabricating biological 3D   crystal that generates sound waves inside the printhead
            structures due to its capability to process biomaterials   in response to a controlled voltage. These sound waves
            of  various  viscosities  and  produce  high-density cell   divide the liquid biomaterial in the printhead into several
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            structures or large-scale 3D structures.  However,   droplets and enable them to be ejected at a constant speed.
            extrusion-based bioprinting systems face challenges   When a softer sound field is formed, the droplets exhibit
                                                               high precision and directionality, leading to enhanced cell
            in extruding biomaterials with very low viscosities,   survival. 82,83
            rendering  it  difficult  to  maintain  the  shape  of  a  3D
            structure. Additionally, issues such as nozzle clogging   These inkjet printing methods are widely employed
            or cell survival concerns may arise when extruding   because  they  can  be  used  for  printing  low-viscosity
            biomaterials with high viscosities, leading to potential   biomaterials and exhibit high cell viability. Additionally,
            challenges associated with high shear stress. 78   inkjet printing is advantageous for manufacturing small


            Table 2. Conventional 3D bioprinting methods and bioink requirements
             Bioink requirements                        Conventional 3D bioprinting methods
                              Extrusion-based            Inkjet                    Laser-assisted
                                    7
             Bioink viscosity  30–6 × 10  mPa⋅s          <10mPa⋅s                  1–3 × 10  mPa⋅s
                                                                                         2

             Cell concentration  High                    Low                       Medium
                                                            6
                                                         (<10  cells/mL)           (~10  cells/mL)
                                                                                      8
             Resolution       200–1000 μm                10–50 μm                  10–100 μm
             Cell viability   ~90%                       ~85%                      ~95%
             Advantages       Wide choice of materials; simple    High speed; low cost  High cell viability; high repeatability;
                              process; good printability and fidelity              high efficiency
             Disadvantages    Nozzle blockage; long printing time  Few materials; low printing accuracy;   Requirement of the laser source;
                                                         small structure           complex workstation
             Reference        184                        185                       186


            Volume 10 Issue 1 (2024)                        26                          https://doi.org/10.36922/ijb.1972
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