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

of tumor pathogenic mechanisms, composition, and characteristics. These transplanted tumors differ not only
physical properties, contributing to one-sixth of the deaths from those in humans, but also from those in the same
worldwide. It is pathologically heterogeneous between batch of individual mice. The discrepancy in transplanted
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affected individuals. Cancer, subject to multiple factors, tumors poses a challenge to researches of drug properties.
including cellular components, non-cellular components Separately, genetic intervention in knockout mice may
(e.g., cytokines and signaling pathways), and their promote tumor growth, which adds a layer of ambiguity
interactions, undergoes relentless evolution. Aside from with regard to the pathological outcome stemming from
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eradicating tumor cells, cancer treatments have a bearing the transplanted human tumor. Therefore, these obstacles
on factors in the entire tumor microenvironment, which pose a hindrance to accurate prediction of drug toxicity
are related to tumor growth. As the most common cancer and safety using animal models. Of note, only a measly
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therapy, chemotherapy acts directly on the deoxyribonucleic 8% of the drugs tested in animal experiments successfully
acid (DNA) in tumor cells to prevent cell growth or impede entered clinical trial phase I for further evaluation, and
specific signaling pathways. Difficulty in targeting specific most positive results stemming from animal experiments
signaling pathways spurs on the development of drugs do not necessarily translate into the same success rate
from complicated sources that have a potential to impact in human trials. Animal models that are easily mutable
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various mechanisms. Drug development involves a long and ethically challenging in experimental settings do not
study cycle, high costs, and a high failure rate of up to represent an ideal approach in drug discovery process.
50% in preclinical studies. Drug screening is a crucial Given these drawbacks, the amalgamation of
3,4
component of drug research and runs throughout the drug extracorporal manufacturing technologies and internal
research process. The primary objective of drug screening tissue simulations becomes the focus of research. Three-
is to identify any potential side effects of the drug to assess dimensional (3D) bioprinting, one of the additive
its safety profile and evaluate its therapeutic efficacy in manufacturing technologies, precisely deposits bioink
animal or human subjects. Moreover, persistent drug from animal or non-mammal sources in a layer-by-layer
exposure will give rise to drug resistance, which warrants fashion. This technique enables the fabrication of organ
more in-depth investigations in drug screening models.
or disease models with microenvironment features, which
Traditional methods for drug screening include two- will gradually replace 2D culture and animal models. The
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dimensional (2D) cell culture, which features monolayer arrangement and geometry of organ-like or disease-like
cells having strong proliferative capacity with applanate models are automatically finished through 3D bioprinters
and stretched shapes. 2D cell culture cannot accurately controlled by a computing system. Genetic information,
reflect the real cell–cell and cell–matrix interactions, and, cells, and factors capable of performing internal functions
thus, is unable to portray various microenvironments are incorporated to enhance physiological relevance. Most
within the human body. The culture conditions offered importantly, 3D culture integrates the crosstalk between
by the existing 2D culture methods cannot sufficiently biological components, tumor metastasis, and vascular
support the maturation of cultured cells into models that formation, providing more accurate insights through
closely recapitulate the physical characteristics of lesions drug resistance studies and presenting complex responses
or organs in vivo, thus decreasing the representativeness of to anti-tumor drugs. Nevertheless, a limitation of
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the in vivo tissues. The 2D-cultured cells may not exhibit 3D-bioprinted constructs is that they are unable to remove
resistance to the applied drugs, yielding inaccurate data in metabolic waste efficiently, and the nutrients they possess
drug resistance studies. are not evenly distributed, resulting in lower cell viability
5,6
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Animal models stand as the gold standard method for and shorter culture times.
preclinical drug screening. On the one hand, these models “Lab-on-a-chip” based on microfluidic technologies
enable the exploration of disease mechanisms and lesion recapitulates all laboratory operations on a micrometer-
status, which aids the assessment of drug potential. On level chip. The constructs on a chip can also mimic tissue
the other hand, animal models can be utilized to evaluate or organ microenvironments equipped with mechanical
toxicity, efficacy, and pharmacokinetics of new treatments, features such as blood flow, heartbeat, and breathing.
for confirming their eligibility for the subsequent clinical Controlled perfusion in microfluidic channels overcomes
studies. However, there are limitations to using animal the issue of uneven nutrient diffusion in 3D bioprinting, and
models in drug screening. Tumor-implanted animals cannot various organs can be connected on a chip. The interactions
accurately replicate the effects seen in humans with tumors between organs are developed on this basis. Furthermore,
because of genetic, immunological, and cellular variations. the voluntary deposition of bioink on microfluidic chips
Additionally, orthotopic mice models transplanted with lessens the tedious steps of microprocessing and increases
human tumors are unable to faithfully recapitulate tumor the possibility of automation in microfluidic chips. 12,13

Volume 10 Issue 3 (2024) 173 doi: 10.36922/ijb.1951