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




            complexity and heterogeneous  interconnections. The   observed in actual organs, difficulties in maturing different
            heart serves as the central pump, driving the flow of   cells within a single platform, and the preservation of
            blood. Consequently, any collapse or dysfunction within   the structure of large-scale constructs.  Consequently,
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            the cardiovascular tissue can lead to issues in the body’s   comprehensive research  is  underway to address  all
            circulation of substances.  Cardiovascular disease (CVD),   aspects of 3D bioprinting, ranging from advancements
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            notorious for its challenging treatment, stands as the   in printer components to biomaterials. This includes the
            leading cause of mortality worldwide.  Among the most   development of multi-material extrusion nozzles, in-bath
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            severe forms of CVD is atherosclerosis, characterized by   printing methods, photocuring hydrogels, and sacrificial
            the accumulation of plaque on artery walls due to elevated   hydrogels. 20,59,92,161  In addition, active research is ongoing
            levels of cholesterol and triglycerides. Hence, a precise in   regarding various sensors that can be integrated into a
            vitro model that accurately reflects both the severity of the   chip to monitor physiological changes in the organ-on-a-
            disease and the intricacies of the cardiovascular system,   chip in real time.  In the near future, there is a promising
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            encompassing the myocardium and the heart, is necessary.   prospect of developing a human-on-a-chip that replicates
            To address this need, Zhang et al. developed a composite   the entire human body, encompassing multiple organs,
            bioink capable of aligning endothelial cells and used 3D   through advancements in 3D bioprinting. The integration
            bioprinting to create an aligned myocardial in vitro model   of diverse organ-on-a-chip platforms through 3D printing
            capable of spontaneous contraction.  The significance   allows for innovative experimental research. These models,
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            of this study lies in the achievement of myocardium   designed to simulate various organs, prove invaluable for
            alignment and contraction via the development of a bioink   studying the mechanisms underlying specific pathologies
            facilitating  cell  control  and  a  3D  bioprinting  method.   and their effects on the entire organ system in vitro. 163
            However, it is essential to note that the resulting structure
            is relatively simple and does not fully replicate the various   4. Limitations and future perspectives
            tissues constituting the heart or other cardiovascular   Three-dimensional  bioprinting  is  adept at processing a
            organs. Additionally, advancing the model requires the   variety of cells and biomaterials into diverse shapes, making
            incorporation of sensors capable of monitoring heart   it  particularly  suitable  for  fabricating  organs-on-a-chip
            contraction. 20                                    that require complex structures and microenvironments.
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               Numerous placental diseases, including gestational   Organs-on-a-chip fabricated by depositing cells and
            trophoblastic disease and preeclampsia, pose significant   bioinks through 3D bioprinting techniques, such as inkjet,
            risks to both the fetus and the mother.  However, owing   laser-assisted, and extrusion-based bioprinting methods,
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            to the unique circumstances of pregnancy and the distinct   have demonstrated the capacity to precisely mimic both
            structure of the placenta, there exists a scarcity of models   the structural and functional features of various human
            capable of reproducing these pathologies. Consequently,   organs.  The utilization of diseases-on-a-chips, which are
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            an urgently needed in vitro model is essential for safe and   applications using normal organs-on-a-chip, has proved
            effective study.  Kuo et al. fabricated a 3D in vitro placenta   the technology’s potential to achieve pathophysiological
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            model, employing 3D bioprinting to create spiral arteries   relevance and its applicability to drug screening.  While
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            and strategically arranging the constituent cells.  However,   3D bioprinting holds substantial potential for organ-
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            this model had limitations as it failed to incorporate all   on-a-chip  fabrication,  its  widespread  applications  face
            the various layered membranes of the placenta, such as   limitations posed by several challenges.  The following
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            the chorionic membrane. Additionally, it did not simulate   discussion addresses challenges associated with current
            the contraction of the placenta or the specific structure   biomaterials and 3D bioprinting technology for organ-on-
            of the villi, thereby falling short of realizing the complex   a-chip fabrication, as well as issues with the organ-on-a-
            microenvironment of the placenta (Figure 6B). Therefore,   chip itself. Moreover, proposed approaches to overcome
            in the advancement of placenta models, ensuring a smooth   these issues are presented.
            supply of cell sources that constitute the placenta and the   Biomaterials play a significant role in establishing the
            selection of flexible biomaterials capable of simulating the   microenvironment of organs-on-a-chip.  However, the
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            unique shape and contraction of villi become imperative.
                                                               suitability of biomaterials for 3D bioprinting is constrained
               Additionally, organs-on-a-chip have been developed for   owing to their physical properties and limited crosslinking
            various organs, such as gut-on-a-chip, airway-on-a-chip,   methods.  Additionally, achieving an organ-specific ECM
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            and lung-on-a-chip. 158-160  The utilization of 3D bioprinting   composition and implementing a microenvironment
            technology is widespread in producing precise 3D in vitro   present  inherent  challenges.  Therefore,  the  development
            models for these applications. However, challenges persist,   of a method for mapping the physiological ECM specific
            such as the accurate implementation of the complexity   to each organ and reproducing the ECM composition of


            Volume 10 Issue 1 (2024)                        36                          https://doi.org/10.36922/ijb.1972
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