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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

