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International Journal of Bioprinting                              Bioprinted organ-on-a-chip with biomaterials




            individual organs becomes imperative. Additionally, it is   and mechanical properties suitable for the cell.
            necessary to explore the creation of new biomaterials with   Improving the rheology and flow properties of the
            physical properties conducive to 3D bioprinting. This can   bioink becomes essential to ensure the stability of
            be achieved through the chemical or physical treatment of   the printing process. This involves refining printing
            existing biomaterials, which provides a higher degree of   conditions and regulating the instantaneous flow
            freedom in designing organs-on-a-chip.                  of bioink via appropriate rheological modeling and
               The advantages and disadvantages of conventional 3D   automatic control systems. 168
            bioprinting technologies are summarized as follows:   Organs-on-a-chip  demand  attributes  such  as
            (i)   The inkjet printing method exhibits significant   high  accuracy,  processing  speed,  resolution,  and
                 potential for high-resolution cell printing using   biocompatibility to effectively replicate physiological
                                                                        170
                 droplets. However, constructing a 3D structure   conditions.  Additionally,  to  achieve  enhanced
                 poses challenges owing to stacking limitations. 33  biomimicry or create large-scale structures, the utilization
                                                               of a more diverse range of biomaterials is essential.
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            (ii)  Stereolithography proves suitable for manufacturing   Therefore, advancements in printing speed, precision, and
                 microfluidic devices with smooth surfaces and has   the development of new dispensing technologies become
                 found extensive use in organ-on-a-chip fabrication   imperative.  Meeting  these  requirements  often  involves
                 requiring high resolution. However, it is unsuitable   the integration of existing 3D bioprinting technologies or
                 for simultaneous multimaterial printing, where   leveraging engineering technologies from other fields. For
                 multiple biomaterials  are  printed  on a  single   example, Brassard et al. demonstrated the production of a
                 platform. 26                                  macroscale tissue block representing microscale structures

            (iii)  Extrusion-based printing can be used for producing   by combining extrusion-based and inkjet bioprinting
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                 bulky  3D  structures  or  facilitating  multimaterial   technologies.  Kim et al. successfully fabricated a
                 printing. However, it is characterized by relatively   large centimeter-scale structure using light-activated
                 low resolution. 166                           dECM bioink manufacturing technology combined with
                                                               extrusion-based  bioprinting.   Additionally, altering
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               In the development of bioinks for 3D bioprinting,   the shape or function of 3D-printed structures can
            careful consideration must be given to the rheological   be accomplished by increasing the degree of freedom
            properties of the material, as they significantly affect both   through the application of external stimuli, a concept
            the 3D bioprinting process and the quality of the resulting   realized through 4D printing technology.  Kirillova et al.
                                                                                                173
            organs-on-a-chip.  In most 3D bioprinting methods,   successfully  constructed  hollow  self-folding  tubes  using
                          167
            the bioink is delivered to the plate through a nozzle,   4D-printed shape-modifying biopolymer hydrogels. 174
            necessitating attention to characteristics such as shear
            thinning, yield stress, and rapid structural recovery upon   Additionally,  achieving  accurate  real-time  control  of
            stagnation when the bioink passes through the nozzle.  In   printing environmental parameters, such as humidity or
                                                      168
            the context of 3D bioprinting, particularly extrusion-based   temperature, proves challenging in current 3D bioprinting
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            printing, several key characteristics must be considered:  systems, leading to issues with manufacturing precision.
                                                               Therefore, it is imperative to establish a printability
            (i)   The rheological properties of the bioink significantly   database for various biomaterials and implement real-time
                 impact the proliferation of encapsulated cells, as   automatic control within 3D bioprinting systems.
                 well as the morphology and stability of the resulting
                 tissue.  Therefore, bioinks must possess appropriate   The integration of the abovementioned technologies
                      169
                 viscosity and rheological properties.         facilitates  the  fabrication  of  organs-on-a-chip  that
                                                               closely emulate the functions of real organs. Despite this
            (ii)  Non-Newtonian effects, such as rapid structural   progress, challenges related to commercialization costs and
                 recovery following strong shear thinning, are   manufacturing difficulties remain. The development of
                 important for minimizing cell damage while    streamlined systems and the reduction of commercialization
                 maintaining  the  stackability  of materials—an   costs represent primary challenges in this field.
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                 indispensable consideration during the development   Significant  strides  have  been  made  in  the  successful
                 of bioink.
                        168
                                                               development and  commercialization  of 3D  printers and
            (iii)  The stability of a bioprinted organ-on-a-chip is   bioinks.  Companies such as EnvisionTec, CELLINK,
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                 intricately tied to its rheological properties.  To   Organovo, and Rokit specialize in manufacturing 3D
                                                      19
                 prevent structural deformation, it is imperative   printers using extrusion-based methods and directly cater
                 to develop a bioink with high shape fidelity   to the regenerative medicine market.  These printers
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            Volume 10 Issue 1 (2024)                        37                          https://doi.org/10.36922/ijb.1972
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