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International Journal of Bioprinting                             Review on Hybrid Biomanufacturing Systems


            bioink , which improves the reproducibility of the droplet   Pneumatic deposition process is simple and effective
                 [34]
            ejection and makes BioLP more efficient than other laser‑  but can be slow due to the limited force applied to highly
            assisted biomanufacturing techniques.              viscous material, which results in long printing time,
              Laser-assisted biomanufacturing techniques have been   presenting limitations in precisely controlling the volume
            widely applied in tissue regeneration due to its advantages   of material deposited, especially during the lag time when
            in high printing resolution, high reproducibility, and   the pressure is switched on and off. Also, the long printing
            feasibility for multi-biomaterial and biomaterial/cell   time for high viscous material can reduce cell viability
            mixtures processing . Bourget et al. used LGDW to print   in the bioink. The limitation factor of the mechanical
                            [35]
            human umbilical vein endothelial cells (HUVECs) and   assisted extruders is related to the shear stress-induced
            human bone mesenchymal stem cells (HBMSC) on to    deformation during the deposition process, which has
                                                                                          [44]
            a collagen hydrogel substrate . This study showed that   a negative effect on cell viability . High temperatures
                                    [36]
            LIFT allows easy patterning of cells on a collagen matrix,   are typically required to process high-viscosity polymers
            and endothelial cells tend to migrate randomly without   using  standard  extrusion  methods,  and  subsequently,
            HBMSCs but would stay within the printing lines when   screw-assisted extrusion, which can be termed precision
            in co-culture. Moreover, Keriqual et al. (2017) conducted   extruding deposition (PED). PED was initially developed
                                                                                           [45]
            in situ LIFT to print mesenchymal stromal cells for bone   by Bellini et al. at Drexel University . The system consists
            tissue regeneration . The  in  vivo results revealed that   of a rotational screw, driven by stepper motors, to mix
                           [37]
            regeneration is homogeneous throughout the defect and   and force the material out of a nozzle. Almeida  et al.
            long-term cell viability and proliferation was maintained   (2010) improved this design by including an additional
            up to 42 days post implantation.                   temperature-controlled material chamber in which
                                                               the material can be liquefied and fed into the screw
              The higher cell viability achieved by laser-based   chamber  using  air  pressure .  High-viscosity materials
                                                                                      [46]
            biomanufacturing, as compared with that in inkjet printing   are  more suitable  to be processed  with  this  technique
            and material extrusion, is due to non-contact between the   using lower temperatures, which are less likely to induce
            dispensing  head  and  bioink.  Furthermore,  laser-based   material degradation in the polymer . For example, a
                                                                                              [47]
            biomanufacturing is capable of high-viscosity bioink   polycaprolactone (PCL)-graphene composite scaffold
            deposition and high printing resolution, allowing complex   has been printed using screw-assisted extrusion, which
            patterning and fabrication of structures that mimic the   has proven that it is difficult to extrude using pneumatic
            complexity of tissues and organs. However, despite all   or piston-assisted extrusion with high speed and high
            the above advantages, laser-based biomanufacturing   precision .
                                                                      [48]
            shows great capabilities for cell patterning but has
            difficulty  in  building  large  3D  structures,  especially  in   The availability of a large variety of material types and
            the vertical direction . The equipment used in laser-  viscosities, such as high-viscosity biomaterials and bioinks
                              [38]
            based biomanufacturing is also more expensive due to the   with high cell densities, that can  be used in  extrusion-
            complexity of installing lasers and optics. Moreover, the   based biomanufacturing is an apparent advantage of
                                                                               [49]
            heat generated from laser or light energy will negatively   using the technique . However, a big drop in pressure,
            influence the cell survival, proliferation and degradation   especially for the screw-based bioextrusion method, can
            in  the  tissue  constructs .  The  introduction  of  new   be harmful for the cell viability due to the disruption of
                                 [39]
                                                                               [50]
            biomaterials to create crosslinked composite materials is   the  cell membranes . Moreover, other  drawbacks  also
            beneficial for cell survival, which may help the development   include the potential risk of nozzle clogging and relatively
                                                                                               [51]
            of laser-based biomanufacturing .                  low printing resolution (200 – 1000 µm) .
                                      [40]
            2.2. Material extrusion                            2.3. Vat photopolymerization (VP)
            Material extrusion is a versatile technique that operates   VP uses photopolymerization to cure the liquid ink hosted
            with materials in the form of filaments, pellets, pastes, and   in a vat into a volumetric construct in a  layer-by-layer
                                                                     [14]
            solutions. Different methods, such as pneumatic (pressure),   manner . It comprises mainly three categories:
            mechanical (piston), and screw-assisted systems, are   (i)  SLA . As the primary technique of VP printing, SLA
                                                                      [15]
            currently being used in material extrusion . These    uses a laser beam that sweeps around to polymerize
                                                  [13]
            printing methods allow for the processing of a wide range   single lines of the ink to complete each layer in a raster
            of  biomaterials  and  compositions,  including  polymer-  scan mode. In the process of SLA printing, a series of
            ceramic  composites,  polymer-carbon  nanomaterial    UV light patterns are projected onto a vat containing
            composites, hydrogels, and bioinks containing cells and   the liquid ink to achieve photocrosslinking across the
            growth factors [41-43] .                              build volume.


            Volume 9 Issue 1 (2023)                        323                      https://doi.org/10.18063/ijb.v9i1.646
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