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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.
171
(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
172
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.
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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.
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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
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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

