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International Journal of Bioprinting                          Bottom-up and top-down VAT photopolimerization




            and channels, in which cells can expand and grow, and   generally uses ultraviolet (UV) light to selectively solidify
            finally, build functional organ parts  in vitro [6-8] . However,   a light-sensitive bioink layer by layer. It can produce 3D
            native tissues and organs possess inherent heterogeneity in   structures with good resolution and can be combined with
            physical, mechanical, and biological properties . In order   hydrogel-based bioinks, allowing significant control over
                                                 [9]
            to capture this heterogeneity, the combination of multiple   the resulting matrix properties [24,25] . Similar to SLA, DLP
            materials with distinct mechanical properties as well as   is a technology based on the layer-by-layer crosslinking of
            different cell types is necessary. Recent advancements in   photosensitive inks by exposure to a projection mask .
                                                                                                           [26]
            tissue engineering evidenced the fabrication of multi-tissue   The projection of light can be achieved via liquid crystal
            models, which can closely imitate organ-to-organ interfaces,   displays (LCDs) and digital micromirror devices (DMDs),
            in order to investigate the complex interactions and monitor   which focus the light as square voxel patterns on the surface
            the dynamic responses of multiple organs to pharmaceutical   of the ink . Due to the non-contact nature of light, SLA
                                                                       [27]
            compounds. Multi-tissue microfluidic platforms have been   and DLP are attractive bioprinting methods because they
            developed to model lung , liver , intestine , kidney ,   do not have the problems associated with contact-based
                                                [12]
                                                        [13]
                                      [11]
                                [10]
            brain , and heart . Thus, it becomes apparent that the use   bioprinting (e.g., clogging, shear stress) [22,28] .
                [14]
                          [15]
            of 3D bioprinting for the recreation of microphysiological
            systems of tissue–tissue interfaces can expand the    Current bioprinting methodologies are mostly limited
                                                                                                   [29]
            capabilities of the existing tissue models [16-18] .   by printing single material tissue models , and the
                                                               available multi-material are less cost-effective and time-
               The bioprinting technologies currently used for the   consuming . Additionally, they are not able to bioprint
                                                                        [30]
            fabrication of living tissue models can be divided into three   cell-laden constructs with multi-material components
            broad  categories,  namely  extrusion-  and  jetting-based   in  relevant  clinical  dimensions.  Extrusion  bioprinting
            bioprinting as well as VAT photopolymerization. Extrusion   was demonstrated for multi-material human umbilical
            bioprinting uses pressure generated by a pneumatic or   vein endothelial cells (HUVECs) . Likewise, 3D human
                                                                                         [31]
            mechanical system, or a combination of both, to deposit   renal proximal tubules were printed for replicating
            cell-loaded bioinks . It is a relatively inexpensive process   a human kidney-on-a-chip and retained viable for 8
                           [19]
            that allows high printing speeds and provides precise   weeks . The bioprinting time of the methodologies is
                                                                    [32]
            control over the porosity and mechanical properties of   in the range of a few hours, indicating that extrusion 3D
            the final constructs, making it an attractive method for   bioprinting lacks acceptable printing time and resolution of
            producing harder tissue scaffolds. Extrusion has been   microtissue material fabrication; therefore, multi-material
            used at high cell densities, but the choice of available   methodologies able of using multiple bioinks for the rapid
            biomaterials is relatively limited, as the rheological   manufacture of hydrogel-based constructs are still required.
            properties of the biotins are critical to cell viability.
            Apart from the properties of the bioinks, the printing   More recently, it has been demonstrated that a multi-
            speed directly affects the shear  stress to which  the cells   material DLP-based bioprinter was developed to fabricate
                                                                                      [26]
            are subjected during printing. Therefore, the resolution   high-resolution microtissues . In addition, Miri  et al.
            of the final scaffold may need to be limited to avoid cell   used a multi-material DLP bioprinting of hydrogel-based
                                                                              [28]
            apoptosis . On the other hand, inkjet bioprinting is based   microfluidic chips , while Zhu  et  al. applied a similar
                   [20]
            on continuous (continuous inkjet, CI) or discrete (drop-  DLP bioprinting for making a pre-vascularized (channels
                                                                                              [33]
            on-demand, DOD) deposition of a liquid biomaterial   seeded by HUVECs) tissue models . These studies
            onto a substrate. This bioprinting method has been used   suggest the capacity of DLP-based bioprinting for creating
            to produce cell-loaded scaffolds with high resolution and   multi-material microtissues [34,35] .
            good shape fidelity, which are good candidates for soft   Most  light-based  bioprinters  are  based  on  a  “top-
            tissue bioprinting . However, the major disadvantage of   down” printing approach, where a UV light source located
                          [21]
            inkjet bioprinting is the risk of needle clogging, which can   below the bath of the photosensitive biomaterial is used
            interrupt the printing process and expose the cells to high   to selectively polymerize it to generate a 3D structure in
            shear stress, negatively affecting cell viability.  a layer-by-layer fashion . The “top-down” configuration
                                                                                  [36]
               VAT photopolymerization bioprinting technologies   has been shown to work well with hard materials, resulting
            include light-based methods, namely laser-based    in scaffolds with enhanced mechanical properties that can
                                                                                    [37]
            bioprinting, stereolithography (SLA), and digital light   provide sufficient support . However, processing softer
            processing (DLP) . Laser-based printing offers good   materials  with  this  method  is  still  challenging.  Recent
                          [22]
            resolution and high fabrication speeds but has not been   studies reported an alternative approach, by placing the
            successfully combined with cells because of the problems   light source for the projection of the printing pattern above
            associated with using laser light with living material . SLA   the photosensitive material [38,39] , introducing a “bottom-
                                                    [23]
            Volume 10 Issue 2 (2023)                       532                                doi: 10.36922/ijb.1017
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