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14.2 BIOPRINTING                                     271

































           FIG. 14.1  Representative drawings of the three most common bioprinting methods: (A) laser-based, (B) inkjet-based, and (C) extrusion-based
           bioprinting. (D) Representative direct and indirect bioprinted structures. In direct bioprinting, cell containing base material is printed according
           to the designed 3-D structure; in indirect bioprinting, a sacrificial level was removed to enable perfusable areas for providing nutrient and gas transfer
           for the encapsulated cells in the bulk structure. (Reprinted with permission from N. Nagarajan, et al., Enabling personalized implant and controllable bio-
           system development through 3D printing, Biotechnol. Adv. (2018).)

           an automated system for extrusion and writing [16]. In the last couple of years, several researchers have tried to use a
           fugitive bioink in extrusion-based bioprinting to create vascular channels [17]. The fugitive bioink is removed after-
           ward by thermally induced reverse cross-linking leaving a network behind [18]. It is well known that this technique is
           very convenient for producing 3-D cell-laden structures. For instance, Bertassoni et al. used extrusion-based bioprint-
           ing for the fabrication of microchannel networks within cell-laden GelMA hydrogels as a model platform. They dem-
           onstrated that the fabricated microchannels resulted in improved mass transport, viability, and differentiation of cells
           in cell-laden GelMA hydrogels [19]. Table 14.1 shows a comparison of bioprinting techniques in which the resolution,
           commonly used materials, gelation speed, advantages, and disadvantages of each technique are presented [10].
              There are two bioprinting approaches that explore engineering vascular networks within the engineered tissue
           constructs through indirect and direct bioprinting, Fig. 14.1D. In the indirect approach, a negative supportive mold
           is created initially, which is then used to cast the desired polymer scaffold through a suitable drying method. Fre-
           quently, freeze-drying approach is used as it causes less shrinkage and can reproduce the designs accurately. In
           the case of direct approach, the scaffolds are produced directly from the model material, through processes such as
           extrusion printing [3].


           TABLE 14.1  Comparison Among Laser-, Inkjet-, and Extrusion-Based Bioprinting Techniques [10]
                        Laser-based                      Inkjet-based        Extrusion-based
           Resolution   High                             Medium              Medium-low
           Materials    Cells in media                   Liquids, hydrogels  Hydrogels, cell aggregates
           Gelation speed  High                          High                Medium
           Advantages   High accuracy, single-cell manipulation,  Affordable, versatile  Multiple compositions, good mechanical properties
                        high-viscosity material
           Disadvantages  Relatively harsh conditions for cells, low  Low viscosity prevents  Shear stress on nozzle tip wall can negatively affect
                        scalability, low viscosity prevents buildup in  buildup in 3-D, low  the cells, limited number of biomaterials can be used
                        3-D                              strength




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