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International Journal of Bioprinting                                 3D bioprinting for organoid-derived EVs




            technologies are inkjet bioprinting, laser-assisted   intestinal organoids, demonstrating its potential for
            bioprinting, photocuring bioprinting, and extrusion-based   generating complex tissue structures while maintaining
            bioprinting (Figure 2B). Each of these technologies offers   high  cell  viability. 32,51,52   The  technique  involves  a  three-
            distinct advantages and challenges for organoid fabrication.   part process consisting of a donor-slide (or ribbon),
            A  comparison  of  different  bioprinting  technologies  for   a laser pulse, and a receiver-slide, enabling the gentle
            printing organoids is provided in Table 1.         deposition of biomaterials to preserve cell viability.  One
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               Inkjet bioprinting is widely used for high-throughput   of the key advantages of laser-assisted bioprinting is its
            applications that require detailed structures, such as small,   ability  to  accommodate  various  cell  types  and  bioinks,
            intricate organoids and high-throughput drug screening   which enhances its applicability in tissue engineering and
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            models. 43,44  This process utilizes a thermal or piezoelectric   regenerative medicine.  Despite its advantages, laser-
            actuator to generate droplets of the bioink consistently. 45,46    assisted bioprinting faces several limitations that may
            The technique allows for the deposition of droplets smaller   hinder its widespread adoption. One significant challenge
            than 50 μm in a non-contact manner with high resolution,   is the restricted range of compatible biomaterials, which
            maintaining high cell viability due to low shear stress   limits the diversity of constructs that can be produced
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            during droplet ejection. 47,48  Inkjet bioprinting is used to   using this technique.  Moreover, the high equipment costs
            create detailed tissue models for drug testing and studies   associated with laser-assisted bioprinting setup make it not
            involving sensitive cells, such as embryonic stem cells.    only a complex but also a potentially expensive technology
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            However, challenges such as bioink viscosity control and   to implement, posing a barrier to its accessibility for
            susceptibility to clogging exist, limiting its application with   researchers and institutions looking to adopt bioprinting
            certain tissue types. 49                           technologies.
               Laser-assisted bioprinting is an innovative technology   Extrusion-based bioprinting is versatile and scalable,
            that utilizes laser beams to precisely deposit biomaterials   making it suitable for producing large and robust tissue
            onto substrates, eliminating the need for nozzles   constructs, including various organoid models. 55,56  This
            commonly used in traditional bioprinting methods.  This   technique extrudes bioinks as discontinuous filaments
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            approach enhances printing resolution and cell viability,   using a pneumatic piston or screw mechanism, enabling
            making it suitable for applications requiring high precision   the construction of complex 3D structures layer by layer.
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            and intricate cellular arrangements, such as the creation   The  versatility  of  extrusion-based  bioprinting  lies  in  the
            of detailed tissue constructs and organoids. Laser-assisted   ability to use a variety of bioinks with different viscosities.
            bioprinting  was  used  to  successfully  fabricate  liver  and   This makes it suitable for producing large, complex


            Table 1. Advantages and disadvantages of bioprinting techniques for organoid printing.
             Printing method  Key aspects           Advantages                 Disadvantages            Ref.
             Inkjet-based   High-throughput;        •   High throughput        •   Nozzle clogging      37–39
             bioprinting    drug screening;         •   Low shear stress       •   Viscosity limitations
                            creating detailed       •   Low cost               •   Shear force stress
                            tissue models;          •   High resolution        •   Limited to certain tissue types
                            sensitive cell printing  •   Multiple materials
             Laser-assisted   High-precision;       •   High cell densities    •   High cost            39–41
             bioprinting    suitable for applications requiring   •   High cell viability  •   Complex setup
                            high cell viability     •   Versatility            •   Material limitations
                                                    •   Nozzle-free            •   UV-induced DNA damage
             Extrusion-based   Creating large and robust tissue   •   Scalability   •   High shear stress  41
             bioprinting    constructs;             •   Mechanical strength    •   Low resolution
                            fabricating liver,      •   Versatility            •   Viscosity management
                            kidney, and intestinal organoids  •   Multiple biomaterials form separate
                                                      nozzles
             Photocuring    Creating complex,       •   High speed             •   Material constraints  42
             bioprinting    high-resolution structures;  •   High resolution   •   Costly equipment
                            creating organoid       •   Nozzle-free            •   Layer limitations
                            scaffolds and detailed   •   Supports complex structures  •   UV-induced DNA damage
                            tissue models
             Abbreviation: UV, ultraviolet.


            Volume 10 Issue 5 (2024)                       101                                doi: 10.36922/ijb.4054
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