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3D Bioprinting for Anticancer Drug Screening
Material properties such as mechanical properties, consider the dynamic nature of the TME allowing for the
biocompatibility, and ease of handling limit the choice controlled release of growth factors, and incorporation
of substrates for PDMS. Although PDMS fulfills most of ECM-mimetic biomaterials that mimic native tissues
of the criteria for studying biological mechanisms, it is are challenging and need to be explored in detail [122,138] .
not suitable for hydrophobic drugs including anticancer In addition, the mechanical properties of the tissue
compounds, making it necessary to explore other materials being modeled, such as stiffness and adhesion sites,
that can be molded and printed, such as epoxy resins, off- should also be considered when developing bioinks.
stoichiometry thiol-enes and perfluorinated polymers. To enable the use of tumor-on-a-chip technology, it
For widespread use, the methods that manufacture needs to be coupled with effective tools to enable on-
tumor-on-a-chip platforms should be amenable to scale- chip analysis. However, information on tools and
up activities to facilitate large-scale manufacture, which techniques for on-chip analysis is often lacking. Further
requires investigation of materials and bioinks and a focus research on physical sensors on-chip for the evaluation
on user training. To fully achieve the potential of tumor- of gas exchange, pH levels, and metabolic markers is
on-a-chip devices, various manufacturing, operability, necessary. Standardization of biosensors to allow for use
and regulatory challenges must be solved. in high-throughput assays and to optimize therapeutic
Future work that can facilitate the adoption of performance is another area that needs to be explored
tumor-on-a-chip for high-throughput screening of further. On-chip imaging methods to characterize
potential drug molecules should involve correlation of tumors in terms of size, morphology, and viability can be
the results obtained with tumor-on-a-chip system with achieved by techniques, such as confocal laser scanning
xenograft models or clinical tumor tissues. Validation of microscopy, fluorescence hyperspectral imaging, and
tumor-on-a-chip models is an important step to facilitate integration of optical elements into the microchip,
the widespread use of on-chip technology, improve drug which represent other avenues for analysis [139] . Another
discovery and personalized medicine, and help reduce important area that use of bioprinting and microfluidics
unethical animal testing. Cancer xenograft models that technology requires work on the part of regulatory
mimic the complexity and variability of human tumors can agencies in further and create standardized guidelines
be used to validate tumor-on-a-chip models. Correlation for the requirements of processes for the approval and
between human cancer xenograft in mouse and tumor- clinical translation of bioprinted models [19] .
on-a-chip wherein the tumor-on-a-chip technology can
mimic many of the relevant characteristics of cancer 7. Conclusion
cells and the TME, and host response indicates a progress The fabrication of tumor-on-a-chip has the potential
toward improved drug discovery [131] . The emergence of to reduce the dependence on animal models for cancer
cancer immunotherapy that relies on the patients’ immune research by providing a platform for the screening
system activation has led to research in developing of chemotherapeutic compounds and personalized
immunocompetent tumor-on-a-chip models to understand medicine. Although studies have shown the ability of
tumor-immune system interactions and screen potential these platforms to capture the dynamic environment of
anticancer immunotherapies [132] . The combined effect of tumor-stromal interactions and ECM, challenges related
TME with tumor-associated immune cells under dynamic to manufacturing (bioinks, vasculature fabrications,
conditions will help in providing realistic data outputs for process optimization, and standardization) and regulatory
anticancer screening. Based on the immunosuppressive approval still exist. Advancements in bioprinting
effect of myeloid-derived suppressor cells and regulatory processes such as the development of hybrid printers for
T-cells (Tregs), they should be incorporated into the the fabrication of tissue and chip and the integration of
tissue or tumor cells [133] . Since tumors have markedly biosensors and read-out displays are expected to allow for
different molecular and biological signatures from one the widespread adoption of tumor-on-a-chip for cancer
another which can affect drug efficacy, incorporation of modeling and drug development.
patient-derived cancer cells in the fabrication of tumor
models can be used to recapitulate this heterogeneity. Funding
Few studies have investigated the use of patient cells with
the bioprinting platform, prompting the need for further This work was supported by institutional grants from
research in this area [134,135] . Patient-derived samples have the National Key R&D Program (2020YFF0305101,
been used for chemotherapy drug testing by Mazzochi 2019YFC0119301, 2019YFC0119303).
et al. and Lim et al. wherein similarity was observed Conflict of interest
between drug responses in vitro and in the patients [136,137] .
The optimization of the bioprinting technique can The authors declare that they do not have any competing
use of stimulus-sensitive hydrogels as bioinks which interests.

58 International Journal of Bioprinting (2022)–Volume 8, Issue 4