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International Journal of Bioprinting                               Multi-physical field control inkjet bioprinting




            was achieved. The proposed MFCPIB method did not influence the viability of smooth muscle cells after printing,
            demonstrating the potential for fabricating tissues with high bioactivity.


            Keywords: Piezoelectric inkjet bioprinting; Multi-physical field; GelMA jetting; Temperature-sensitive material;
            3D structure



            1. Introduction                                    but once they are crosslinked, they offer remarkable
                                                               stability and support. The most commonly used method
            Three-dimensional (3D)  bioprinting offers excellent   for crosslinking is ion crosslinking, which involves using
            potential for regenerative medicine.  Current 3D   substances like sodium alginate (NaAlg) and CaCl  or
                                             1
            bioprinting methods mainly include material extrusion,   fibrinogen and thrombin reflection. NaAlg and CaCl  are
                                                                                                          2
            material jetting, and vat photopolymerization bioprinting.    the most commonly utilized materials in this process. 13,14
                                                          2
                                                                                                          2
            Extrusion bioprinting is the mainstream 3D bioprinting
            method  that can  print  high-viscosity bioink.  However,   Table 1 illustrates three methods for crosslinking NaAlg
                                                 3
            cells in bioink are damaged during the extrusion process   and CaCl . The first method is immersion printing. NaAlg
                                                                      2
            because  bioink  is subjected  to  enormous  shear  stress  in   microdroplets are printed on a platform as it descends into
                                                                               15
            the nozzle.  The shear stress of inkjet printing is lesser at   a solution of CaCl .  However, crosslinking in the plating
                     4
                                                                             2
            the nozzle than in extrusion printing. It has been verified   bath risks flushing the printing structure and reducing the
            that appropriate shear force had a negligible effect on cell   printing resolution. The second method combines drop-
            activity, and thus, inkjet printing ensures that cells have a   on-demand (DOD) inkjet printing with a spray-coating
            very  high  survival rate.   Furthermore, the  capability  of   method. Yoon et al. designed an inkjet-spray printing
                               5,6
                                                                                                            16
            3D bioprinting to produce microdroplets at the micron   process to fabricate laminated hydrogel structures.
            scale is conducive for the development of high-precision   However, the spray microdroplets easily dehydrate during
            printing, thereby expanding inkjet printing technology. 7,8   the deposition process, which changes the mechanical
                                                                                      17
            As a result, inkjet printing has attracted much attention in   properties of the structure.  Due to the longitudinal
            biofabrication applications.                       accumulation error, it is difficult for this method to print
                                 9
                                                               the structure with high aspect ratio. The third method is
               However, the disadvantages of inkjet printing cannot   to let the two inks collide in the air, but it is difficult to
            be neglected. Due to the small size of the nozzle, the inkjet   control where the microdroplets fall, resulting in reduced
            printing nozzle can be easily clogged.  In addition, inkjet   accuracy. 18,19  In summary, this method reduces resolution
                                          10
            printers cannot print high-viscosity biomaterials, and   and printing scale, and cannot achieve high aspect
            the materials require suitable mechanical properties for   ratio printing.
            molding after printing.  Therefore, the main problems
                               11
            restricting inkjet bioprinting are ensuring that materials   From the viewpoint of materials, sodium alginate has
            have low viscosity in the printhead and that printed   poor biocompatibility and no cell adhesion ligands that
                                                                                                      20
            objects  maintain  their  structure.   In  order  to  address   are needed to allow cell growth and proliferation.  Gelatin
                                       12
            this issue, most inkjet bioprinting techniques rely on the   methacryloyl (GelMA) is a new biomaterial with excellent
            use of crosslinkable materials. Typically, these materials   biocompatibility that is used in extrusion and photocuring
            remain  in  liquid  state  prior  to  the crosslinking  process,   3D bioprinting. 21-23  It has been verified that GelMA is a
            Table 1. Comparison of the studies between the experimental factors and the aspect ratio of printed structure
             Author    Inkjet type  Method  Materials    Cells  Chemical       Printed structure L ×W × H   Maximum
                                                                modifications  (mm)                 aspect ratio
             Christensen   Piezoelectric  Inkjet–bath  NaAlg, CaCl 2  NIH   N/A  19 × 12 × 12       2
             et al. 15                                   3T3
             Yoon et al. 16  Piezoelectric  Inkjet–spray  NaAlg, CaCl   2  NIH   Characterization of   40 × 105 × 1  0.1
                                            GelMA (≈6 %)  3T3   Saponified GelMA
             Sakurada    Piezoelectric  Inkjet–  NaAlg, CaCl , 2  NIH   N/A    5× 12 × 12.5         2.5
             et al. 18          intersecting             3T3
             Present   Piezoelectric  MFCPIB   GelMA     SMCs   N/A            34 × 20 × 20         4
             work               method      (3%, 5%, 10%)


            Volume 10 Issue 3 (2024)                       360                                doi: 10.36922/ijb.2120
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