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International Journal of Bioprinting                                3D-bioprinted multicellular lung organoids




            network.   This  development  is  critical  for  replicating   bioinks, and the shear forces generated during droplet
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            the oxygenation functions of the lungs, as the vascular   ejection  can  potentially damage cells.   In  addition,  the
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            network facilitates efficient nutrient and oxygen delivery   technique is generally limited to producing relatively thin
            throughout the tissue. Additionally, EBB supports the   layers of tissue.
            integration of high cell densities and various biomaterials,
            making it suitable for the fabrication of large and intricate   3.3. Laser-based bioprinting
            structures. 80,81  It also allows for the incorporation of   LBB,  including  laser-induced  forward  transfer  (LIFT)
            mechanical and biochemical cues within the printed   and stereolithography (SLA), uses laser energy to pattern
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            scaffolds.  The capability to incorporate mechanical and   bioinks with high precision.  These methods leverage
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            biochemical cues within printed scaffolds further enhances   laser energy to pattern bioinks with high precision
            the potential of EBB in tissue engineering applications.  and resolution, making them particularly suitable for
                                                               creating complex and detailed tissue  constructs.  LBB
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               Despite its advantages, EBB typically produces   offers unparalleled control over the microarchitecture
            structures with lower resolution compared to other   of printed tissues, which is essential for replicating the
            bioprinting techniques. The necessity for high-viscosity   intricate structures of lung tissue.  LIFT is a non-contact
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            bioinks, which are required to maintain the structure‘s   bioprinting method that uses a pulsed laser to transfer
            integrity during printing, can lead to challenges such as   bioink from a donor substrate to a receiver substrate.
            nozzle clogging and uneven cell distribution.  Moreover,   The laser energy creates a focused microbubble at the
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            the precision of cell placement and the fine resolution of   interface of the bioink and the donor substrate, propelling
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            the printed constructs are often compromised, potentially   a droplet of bioink towards the receiver substrate.  This
            affecting the overall functionality and replicability of the   technique allows for high precision in droplet placement
            bioprinted tissue.                                 and minimal damage to cells due to the gentle transfer
                                                               process. SLA is a photopolymerization-based bioprinting
            3.2. Inkjet-based bioprinting                      technique that uses a laser to selectively cure photo-
            IBB utilizes droplets of bioink ejected from a printhead   crosslinkable bioinks layer by layer.  This method is highly
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            to build structures layer by layer.  This method is known   precise and can produce structures with intricate details
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            for its high resolution and ability to deposit small volumes   and smooth surfaces. SLA is particularly advantageous
            of bioink with precise control.  Also, this technique uses   for fabricating scaffolds with complex geometries and
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            thermal or piezoelectric actuators to generate droplets   internal features that are challenging to achieve with other
            of bioink, which are then ejected onto a substrate in a   bioprinting methods.
            controlled manner.  Inkjet bioprinting is particularly
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            suitable for creating detailed tissue constructs and   Guillotin et al. demonstrated the use of LIFT to create
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            high-throughput applications. 85                   high-resolution alveolar structures.  The precise control
                                                               offered by LIFT allowed for the deposition of alveolar
               Researchers have utilized inkjet bioprinting to create   epithelial cells in defined patterns, closely mimicking
            high-resolution lung models with precise cell placement.   the  native  architecture  of  lung  alveoli.  This  approach
            Kang et al. developed a 3D pulmonary fibrosis model   enabled the formation of functional alveolar units with
            using inkjet bioprinting.  They layered endothelial cells,   enhanced gas exchange capabilities. Zhu et al. utilized
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            type I collagen, fibroblasts, AT1 and AT2 cells using   stereolithography  to print lung  models with detailed
            inkjet bioprinting technology. In addition, they achieved   vascular networks.  By carefully controlling the laser
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            high precision in cell placement and tissue architecture   parameters and the properties of the photo-crosslinkable
            by creating microfabricated lung models with inkjet   bioinks, they were able to create microvascular structures
            bioprinting. They reported that this layered structure   that supported perfusion and enhanced the functionality
            mimics the alveolar barrier model and can easily induce   of the printed lung tissue. These vascular networks are
            epithelial-mesenchymal transition, which is an important   essential for providing nutrients and oxygen to the cells,
            pathogenic mechanism in pulmonary fibrosis, and identify   thereby improving cell viability and tissue integration.
            biomarker expression, allowing for quick and effective   LBB offers high precision and resolution, enabling
            simulation of pulmonary fibrosis therapeutics.
                                                               the  creation of  intricate  and detailed  tissue  structures.
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               Inkjet bioprinting offers high precision and resolution,   The non-contact nature of LIFT minimizes cell damage,
            making it suitable for fabricating intricate tissue structures.    while the layer-by-layer approach of SLA allows for the
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            It also allows for the use of low-viscosity bioinks, which   fabrication of complex geometries.  These techniques
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            can improve cell viability and functionality.  However,   also  support  the  use  of photo-crosslinkable  bioinks,
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            the low viscosity requirement limits the range of usable   which can enhance the stability and functionality of
            Volume 10 Issue 6 (2024)                        6                                 doi: 10.36922/ijb.4092
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