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3D Bioprinting for Anticancer Drug Screening
mixture of acidic, hypoxic, proliferative, and quiescent The accuracy of bioprinting could be significantly
cells mimicking the tumor structure . They can be improved via the incorporation of a microfluidics print
[71]
engineered to contain different cell types (usually seen head into one of the additive manufacturing techniques
in TME), so that realistic cell-cell physical and signaling (one of the additive manufacturing techniques). This
interactions can be replicated. Spheroid cultures can be microfluidic strategy enables to control the spinning
made by various methods, such as low-adhesion plates, of desirable hollow microfibers continuously on the
hanging drop plates, bioreactors, and micropatterned chip and hence, displays morphological and structural
or nanopatterned surfaces [72,73] . Practical challenges complexity. These hollow structures ease the fabrication
associated with spheroid culture include the production of structure that mimics native tissues as they possess
of uniform size spheroids, the lack of precise control important features such as natural vascular shape, large
overpopulation of different cell types in spheroids, and surface area, high permeability, and high mechanical
[80]
the lack of standardized high-throughput screening assays flexibility . Besides, a low-viscosity cell-laden bioink is
using spheroids Furthermore, the tumor vasculature used as it enhances the migration and alignment of the
[74]
cannot be recreated using spheroids . cells within each microfiber . With a mixture of multiple
[81]
[60]
Organoids are in vitro aggregates produced from biomaterials, a heterogeneous composition microfiber is
stem cells that can self-organize and recapitulate tissue/ created. The creation of distinctive multicompartmental
organ functionality . Embryonic stem cells, induced structures or complex multi-compositional architecture
[75]
pluripotent stem cells, and adult stem cells are all microfibers has great potential in the application of various
[82]
examples of stem cell organoids . Organoids can biomedical fields, such as in cancer drug research .
[76]
accurately replicate in vivo tumor architecture and genetic In addition to 3D bioprinting, other additive
expressions, but they lack some cell types found in vivo manufacturing technologies, such as MEW, allow
and the necessary vasculature for nutrient and waste for the recreation of highly tailored architectures and
transport; therefore, they may only replicate the early scaffold constructs using computer-written programs
stages of organ development, making them unsuitable for for biomedical applications. MEW microfibrous
screening platform replication . polycaprolactone filter was prepared to allow for size- and
[73]
Scaffolds/hydrogels are synthetic 3D structures immunoaffinity-based capture and on-site culture of
constructed of materials with varying porosities, EpCAM-positive cancer cells. The following sections
permeabilities, surface chemistries, and mechanical describe 3D bioprinting in detail with reference to cancer
properties that are meant to simulate the TME . research [73,74] .
[73]
Scaffolds are constructed of biological or synthetic 4. Bioprinting in cancer research
polymers (collagen, Matrigel, gellan gum, hyaluronic
acid, polystyrene, and polycaprolactone). Although, Three-dimensional bioprinting is the process of printing
natural materials allow for a physiologically relevant cells, biocompatible materials, and supporting components
microenvironment for cell attachment and reorganization, into complex 3D living tissues with the required cell/
they suffer from batch-to-batch variability and complex organoid architecture, topology, and functioning using
composition [65,73] . Polymeric scaffolds use hydrogels computer-aided design . Unlike other 3D cell culture
[83]
to generate supports for 3D cultures which can be models discussed in section 3.3 such as spheroids and
hydrolytically or enzymatically biodegraded. Because of organoids that follow a non-guided spontaneous self-
their water content, synthetic polymeric scaffolds offer assembly development of tissues and organs, bioprinting
better repeatability as well as changeable biochemical and allows for spatial control of matrix properties and cells
mechanical characteristics, and allow for the movement in order to more accurately depict the TME and also
of nutrients, oxygen, waste, and soluble components [77,78] . enables designs that simulate tumor vascularization [16,21] .
Scaffolds are routinely made using processes, such as Three approaches are used for bioprinting: biomimicry
3D printing, particle leaching, and electrospinning . that uses bioengineering to replicate the intracellular
[70]
Perfusing the animals and properly dispersing cells on the and extracellular components of organs or tissues,
scaffold are, however, challenging . autonomous self-assembly that relies on cells to drive
[60]
To generate tissue-like structures, 3D bioprinting the desired microarchitecture and functional tissues, and
refers to the additive layer-by-layer construction of fabrication and assembly of mini tissue blocks into a large
diverse materials containing various cells (cancer and construct via rational design, self-assembly, or both [84-86] .
non-cancer cells in the case of anticancer medication Figure 2 shows the trend in the number of
research) and biological components . It allows for the publications related to bioprinting and cancer from 2013
[79]
reproduction of the complex 3D architecture and allows to 2021. These results were obtained from the PubMed
the model complex cell-ECM interactions with the added database using search terms such as “bioprinting,” “3D
advantage of high throughput capability. printing,” “cancer,” “drug screening,” “tumor-on-a-chip,”

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