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International Journal of Bioprinting                             Bioprinted tissue-on-a-chip in drug screening




            bioprinting system; one was filled with the calcium   To fabricate microfluidic chips, it is essential to integrate
            chloride (CaCl ) solution for perfusion, and the other was   a meticulously designed structure, a  propulsion system,
                        2
            inoculated with two types of cells to study their interaction.   a module for cell  culture, and a monitoring unit.
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            Compared with non-perfusion models, this construct had   Fluid-driven systems are categorized into two types: (ⅰ)
            a longer culture duration and better biological relevance. 101   mechanical force, such as flow micropump and pneumatic
                                                               micropump, and (ⅱ) non-mechanical force, such as gravity
               Embedded bioprinting based on extrusion-based                   108
            bioprinting enables the construction of biocompatible   and surface tension.  The base materials for supporting
                                                               artificial tissues or organs, such as polydimethylsiloxane
            entities without introducing heterogeneous components   (PDMS)  and  polymethyl  methacrylate  (PMMA),  enable
            to enhance the mechanical properties. It is manifested in
            two construction ways. The cell-laden bioink with poor   the generation of fluid channels and the insertion of tissue
            mechanical behaviors is bioprinted in a high-density   cultures. PDMS, known for its inexpensive and excellent
            solution (supporting bath) without biological cells to assist   performance, is used in soft lithography, which is the
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            in the consolidation of microarchitectures. The supporting   mainstream in chip fabrication.  The manufacturing
            bath is replaced by culture mediums after the printed   microprocesses for chips containing the pre-fabricating
            constructs are gelated. The GelMA construct printed into   molds, material curing, and plasma treatments are tedious.
            Kapom bath had significantly improved fidelity compared to   3D bioprinting that regulates bore size and microstructure
            air printing.  The other case is the opposite. The sacrificial   in bioprinted models may simplify the complexity of
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                                                               microfluidic chip fabrication. The combination of 3D
            bioink is printed in the support bath that helps the bioink   bioprinting  and  microfluidic  technology  offers  certain
            still during printing and maintain its structure afterward.   advantages:  (ⅰ)  It allows  for the  creation  of biomimetic
            The latter method is beneficial for creating perfusable
            microarchitectures. Embedded bioprinting breaks through   structures, as common polymers like PDMS cannot culture
            the traditional bottom-to-top order of model construction,   cells and replicate organ or tissue microenvironments. The
            thereby  enabling  its  flexibility  in  printing  and  model   use of hydrogels, popular materials in 3D bioprinting,
            constructing. 103,104  Unlike coaxial bioprinting, which supports   can replace PDMS and enable the culture of biomimetic
            the perfusion fluid with bioprinted thin tubes, hollow tubes   structures by combining these two technologies. (ⅱ)
            in embedded bioprinting are perfused with the support of   Automated cell seeding can be efficiently achieved on
            the entire construct, reducing the risk of collapse. Embedded   a large scale without requiring manual seeding. This
            bioprinting also eliminates the gravity effects found in   technique has the potential to construct organ or tumor
                                                               chips with complex structures.  (ⅲ) Controllability can
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            traditional extrusion bioprinting. However, bioprinted   be achieved by manually regulating physical factors such
            bioinks and supporting materials are difficult to match since   as material delivery and velocity of fluid flow, thereby
            support materials with non-Newtonian fluid properties
            should liquify when subjected to shear stress from moving   increasing experimental reproducibility.
            nozzles, but present increased viscosity to support bioprinted   3D bioprinting can be applied in every step during the
            bioink upon stress removal.  Shao et al.  developed a new   fabrication of microfluidic chips, such as mold designs, cell
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            strategy that combined coaxial and embedded bioprinting.   inoculations, and perfusable channel manufacture that is
            The endothelial cells were encapsulated in gelatin and   imbued with perfusates.  Colosi et al. combined these two
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            adhered to the GelMA walls after the gelatin dissolved. The   technologies prior to printing, thereby successfully printing
            problems for nutrient distribution and metabolite removal   the construct with high resolution and porosity via bioink
            caused by non-perfusion were significantly represented in   of lower viscosity. Two different bioinks were converged on
            this research, underlining the importance of integrating   a microfluidic chip into a needle for bioprinting.
            perfusion into bioprinted constructs.
               Interlaced vasculature and numerous substance   4. Applications: 3D-bioprinted perfusable
            transport  routes  exist  in  the  3D-printed  construct  with   models for drug screening
            hierarchical grid, adding uncertainty to the experimental   Mature bioink microarchitectures are constructed using
            results. Although bioprinting can mimic vessels like   3D bioprinting and microfluidic technologies, which
            hollow tubes with perfusable ability, it is still inefficient   serve as efficient and convenient models for conducting
            in dynamic culture, highlighting the need to incorporate   drug screening.
            microfluidic technology.
                                                                  Drug screening, divided into preclinical and clinical
            3.2.4. Microfluidic technology                     screening based on experimental types, plays an essential
            The model that is fully constructed on a chip should be   role in drug development. Although 3D-bioprinted
            cultured for maturation under microfluidic technology.   microfluidic models can express the associated growth


            Volume 10 Issue 3 (2024)                       183                                doi: 10.36922/ijb.1951
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