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International Journal of Bioprinting Bioprinted tissue-on-a-chip in drug screening

in predicting chemotherapy and specific targeted therapy pathological process and drug metabolism in human.
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responses, providing distinctive treatments for individual One of the key advantages of this chip is the use of human-
patients. Hu et al. utilized patient-derived tumor tissues derived cells for each tissue culture. By collecting and
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to develop the superhydrophobic microfluidic chip. analyzing blood mimics in the connected tube, valuable
The morphology and stable mutation of tumors were drug metabolism data can be easily obtained. This data
maintained with passaging, which was consistent with can be used to construct a metabolic model of drugs in
clinical observations. Moreover, this construct generated the human body, which can improve the efficiency of
clinically relevant drug responses after being cultured for first-phase clinical experiments. Furthermore, once the
7 days, showing that patient-derived models have great data obtained from the chip are comparable to that in
potential for drug screening. human experiments, it will be possible to study disease
characteristics in different genders and age groups in a
5.2. Multi-organ microfluidic chips relatively safe manner. The application of human-on-a-chip
Drug metabolism is a crucial factor that determines the can help overcome the challenge of finding diverse types
value of the drug development and the drug toxicity to of experimental individuals for human experiments.
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organs. The liver that houses the enzyme system (CYP450) Additionally, the chip has the potential to expand the
is responsible for about 70% of drug metabolism, and scope of clinical research, including rare diseases and
the intestinal tract is also the primary organ for drug complications with individual differences.
metabolism. The metabolic transformations of drugs
involving hepato-enteric circulation and first-pass 5.3. Personalized administration
metabolism are accomplished by multiple organs. A single- The emergence of diseases such as cancer often arises
organ model is inadequate to reproduce these physiological from dysfunctions in multiple signaling pathways
processes. As the further expansion of the organ-on-a-chip, and abnormalities in multiple organs. Personalized
multi-organ chips have not only been utilized to reveal administration refers to the selection of drugs with
the crosstalk in tissue or organ microenvironments and different mechanisms or administration models for
related mechanisms, but also study drug metabolism and different individuals to achieve the best treatment effect.
tumor metastasis among organs due to their capabilities Combinative administration, from the perspective of
of connecting different organ microarchitectures via the whole microenvironment, combines two or more
perfusion channels that resemble blood vessels. drugs that act on different signaling pathways and organs
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In addition, the pharmacokinetics for drugs includes rather than using a single drug. Moreover, combinative
four processes: absorption, distribution, metabolism, and administration can reduce the dose of a single drug,
elimination (ADME). Data collected from multi-organ thereby attenuating drug toxicity and the potential for drug
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chips can be used to construct the pharmacokinetic- resistance. Nevertheless, combinative administration has
pharmacodynamic (PK-PD) mathematical model, the disadvantage of drug–drug interactions. The bioprinted
which can predict the ADME processes for different microfluidic models can also study the interaction
administration routes and metabolic pathways. To among drugs with different mechanisms through toxicity
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study the uptake and metabolism characteristics of anti- evaluation. Wan et al. testified the difference between
cancer prodrugs in the liver, Shinha et al. inoculated single and combined administrations and analyzed
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hepatocytes and cancer-associated cells in two blocks on a synergistic effect of drugs in combined administration.
chip, respectively, constituting the disease-targeted model. Therefore, bioprinted chips can not only verify the optimal
In another example, tissues from heart, bone, liver, and therapy regimen for each patient but also analyze the
skin were selected owing to their distinctive properties interactions among drugs with different mechanisms.
and significance. The mature models were cultured and
transplanted onto the tissue chip and connected by the 6. Conclusion
flow of blood vessels. Not only did this construct express The integration of 3D bioprinting and microfluidic
more biomarkers, but it also allowed the establishment of technologies has become a megatrend for accurately
PK-PD models and study on treatment regimens as well as modeling tissues or organs in vivo. In the case of tumors,
drug metabolism. This construct was found to be superior the in vitro microarchitecture is based on the interactions
to simple mixed multi-tissue models. 139 between different cell types, which reproduce physical
Human-on-a-chip refers to human tissue cultures features and even bionic behaviors of TME. This combined
connected in series by a vascular analog on a single chip. engineering technology is crucial for implementing these
This approach enables the study of complex interactions characteristics. Gel-based bioinks that imitate the material
among multiple organs, facilitating the exploration of composition in the microenvironment are deposited into

Volume 10 Issue 3 (2024) 189 doi: 10.36922/ijb.1951