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Fang, et al.
successfully implemented in the 3DPF model. Because anthracycline antitumor medication) and paclitaxel were
of biomimetic transport and a 3D cell environment, the assessed by assessing MDA-MB-231 cell death, vascular
3DPF model’s pharmacodynamic results highly resemble permeability factor (VEGF) expression, and NAD+
those of animal trials. The 3DPF model may also be used expression for cell proliferation. This platform was
to investigate the toxicity and metabolism of different feasible to screen antitumor drugs and can be integrated
antibody-based medicines. The importance of including with conventional screening procedures [130] .
fluid flow dynamics in 3D printed models is shown by
these findings [127] . 6. Challenges and future directions
Mi et al. developed a breast tumor-on-a-chip device The highly complex and dynamic nature of tumors
by using inkjet bioprinting on a microfluidic chip [128] . necessitates the development of a suitable biomimetic
MDA-MB-231 cells (human breast adenocarcinoma platform to screen anticancer drugs that recapitulates
cells) and endothelial cells (HUVECs) were printed on the TME. Thre-dimensional bioprinting has emerged
a PDMS chip made by soft-photolithography. The cells as a suitable fabrication method that can be integrated
showed good viability post-printing and this system with microfluidics to create tumor-on-a-chip platforms
was then used to test the responses of the cancer cells that can be used via a high-throughput method for
to paclitaxel, a microtubule-stabilizing drug which is anticancer drug screening. Bioprinting offers special
expected to interfere with the migration capacity of cells. benefits since it enables the simulation of ECM, cells, and
It was observed that paclitaxel caused a dose-dependent other biomaterials’ spatial dispersion and layer-by-layer
decrease in cell migration ability. This platform has the assembly. The development of organs, or specifically
potential to be used for cell analysis, cancer development, tumor cells in this case, can also contribute to personalized
and drug screening and metabolism [128] . medicine due to their ability to recreate patient-specific
Yi et al. [129] fabricated a patient-derived glioblastoma- TMEs. Despite these advantages, bioprinting suffers
on-chip. In this study, patient-derived tumor cells, vascular from some challenges that need to be overcome before
endothelial cells, and decellularized ECM from brain it can be used widely. Resolutions to problems with
tissue were bioprinted in a compartmentalized cancer- printing efficiency, printing resolution, and repeatability
stroma concentric ring structure that maintains a radial as well as standardization of cell sources and biomaterials
oxygen gradient to mimic the structural, biochemical, are necessary to ensure the adoption of bioprinting
and biophysical features of the tumor and represent the technology. Polymer choices for bioprinting are limited
heterogeneous ecology of glioblastoma tumors using and there is always a risk of drug degradation upon
extrusion-based printing. The bioink was made up of heating. Although bioprinting can be performed in an
brain decellularized ECM (BdECM), which solidified aseptic environment, sterilization of the finished product
after deposition and served as a cell-supporting matrix. is usually performed which can cause heat and light-
The capacity of GBM-on-chip to replicate therapy effects induced degradation of polymers. Regulatory concerns
in patients after chemoradiation and temozolomide (TMS, exist regarding the approval of bioprinted constructs as
an anticancer medication) treatment was investigated. these are usually tailored for individual patients and as
The resistance to chemoradiation and TMS for GBM a result do not meet the participant number criteria for
cells produced on GBM-on-chip and clinical patient approval that is usually required by health authorities.
responses were shown to be related, demonstrating that Additionally, most imaging techniques, optical analysis,
this microfluidic technology is viable and precisely and chemical evaluation methods have been developed
reproduces the patient’s treatment resistance. The GBM- for 2D assays, which may not be suitable for analyzing
on-chip can be utilized to find the best medication 3D constructs. Furthermore, processes for the preparation
combination for treating GBM patients, paving the way of tumors need to be optimized and standardized.
for more individualized cancer therapies [129] . Coupling bioprinted tumors with microfluidics
Xie et al. demonstrated the formation of a 3D (tumor-on-a-chip) enables the study of specific
tumor array chip for anticancer drug screening [124] . microenvironmental components on cancer cells,
Electrohydrodynamic 3D printing was used to deposit tumor-stromal and ECM interactions, and allows for
a bioink (gelatin methacryloyl hydrogel, GelMA) obtaining data in real time on a more realistic platform.
containing MDA-MB-231 breast cancer cells on a Advancements in printing technology that enable joint
conductive membrane. In a 3D environment, the cells printing of tissues and cells can help realize tumor-
displayed critical tumor features, such as spreading, on-a-chip technology as a viable method to prepare
survival, and metastasis, as well as distinct cell cycles, screening platforms for chemotherapeutics. Although this
suggesting their potential to spread and metastasize even technology is theoretically sound, practical challenges
after being exposed to high voltage. On this 3D tumor limit its use. Obstacles in technology creation, design,
array chip, the effects of epirubicin (a cell-permeable optimization, analysis, and validation are among them.

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