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3D Bioprinting for Anticancer Drug Screening
and proliferation in the chip. This platform has the delivery and drainage microcirculation channels, the
potential to be used to produce advanced microfluidic TOC-BBL platform is intended to increase knowledge
arrays [124] . of the kinetics of drug and biomolecule transport by
A microfluidic chip was used as a platform for inkjet diffusion .
[13]
printing of HepG2 and U251 (glioblastoma cells) using Cheng et al. used matrix-assisted sacrificial
alginate sodium as the printing matrix by Zhang et al. [119] 3D printing to create a membrane with perfusable
This study was the first to integrate inkjet printing and microchannels using a hydrophobic fugitive ink
microfluidic chip. SU-8 2050, a negative photoresist, was (petroleum jelly-liquid paraffin) placed within a bacterial
used to create the microchip and then PDMS was used to cellulose hydrogel matrix [126] . Bacterial cellulose offers
form the substrate. The viscosity of alginate sodium and various advantages, including a long shelf life that allows
the voltage of the printer were adjusted and optimized to it to be rehydrated to create realistic tissue models, as
allow for the reliable printing of the alginate hydrogel well as a simple and low-cost cell growth substrate,
droplets. Cell suspension with HepG2 and U251 cells high porosity, high water-holding capacity, and good
was prepared in alginate sodium and co-patterned into biocompatibility. To construct a vascularized breast
the channels of the microfluidic chip. A metabolism and tumor model, MCF-7 breast cancer cells were seeded
diffusion study of the model drug, Tegafur (prodrug of onto the device’s paper matrix and HUVECs were
5-fluoro uracil) was performed following inkjet printing employed to fill the surface of the microchannels. The
of the cells. Staining and confocal microscopy were used cells were found to be alive by fluorescence microscopy,
to determine cell viability. Tegafur was metabolized in the and both endothelium and tumor cells multiplied over
co-culture cell system by HepG2 cells to the parent drug, the 14-day culture period. Tamoxifen was administered
5-FU which exhibited anti-cancer effects on U251 cells. into the endothelialized microchannels and the paper
This approach involved spatially controlled patterning of devices were cultured for 48 h to assess drug response.
cells in a microfluidic chip, which can be used for cell The cytotoxicity generated by pharmacological therapy
culture, simulation, and analysis [125] . was demonstrated by confocal pictures. This research
Cao et al. created a tumor model consisting of might lead to a new method for creating simple and low-
a bioprinted hollow blood vessel and a lymphatic cost in vitro tissue models, which could be useful in drug
vessel pair to imitate genuine perfusion and draining screening and customized treatment [126] .
microcirculation systems and enable the investigation of Li et al. [121] established an in vitro hepatoma model
anticancer medication transport kinetics (TOC-BBL) . with extremely homogenous 3D tumor clusters based on
[13]
A blood and lymphatic vascular pair with tumor cells 3D cell printing, co-culture, and microfluidics. The human
implanted within a hydrogel niche was bioprinted using hepatocellular carcinoma SMC-7721 cell line was used
extrusion-based bioprinting with adjustable bioinks to create three models: a 2D model, a 3D printed model
(alginate, GelMA, PEG combinations). The bioprinted (3DP), and a 3D printed + microfluidic model (3DPF).
vascular arteries were housed in PDMS and PMMA The cell clusters were dissolved in a bioink composed of
layers, which also served as a reservoir for the tumor hydroxypropyl chitin and Matrigel and injected into the
cell culture. The bioinks’ mechanical properties, such as microfluidic chips. In comparison to the 3DP model, the
printability, elastic modulus, and rheological behavior, 3DPF model provides a microenvironment with a greater
were optimized by experimenting with different PEG degree of bionics for the cells in the chip, allowing for better
concentrations. Fluorescein isothiocyanate diffusion was credibility of pharmacodynamic test findings. The effect
used to determine the permeability of the vessels and the of Metuzumab, a monoclonal antibody drug, was tested
bioink composition was chosen to mimic the permeability in these models. Cell proliferation, size characterization,
values of native blood and lymphatic vessel pairs in vivo. and antibody-dependent cellular cytotoxicity (ADCC
The TOC-BBL system’s performance was assessed tests) were used to compare the models. The 2D model
using doxorubicin diffusion. Comparative evaluation of was more responsive to medication dosage, which
doxorubicin delivery in one channel (blood vessel only) might be attributed to the distribution of hepatoma cells
or two channels (blood and lymphatic vessel pair) was in the 2D model versus the 3D model, where they are
performed. Cell viability differed between these two aggregated and less likely to interact with drugs. The
configurations emphasizing the importance of inclusion 3D model had better mimicking effect in in vivo tests.
of a draining lymphatic vessel in the TOC-BBL platform. The proliferation efficiencies of the cells were higher in
The surface of the bioprinted vessel pair was seeded the 3DPF model compared to the 3DP model because
with endothelial cells (human umbilical vein endothelial of microfluidic perfusion in the former. Under the same
cells [HUVECs] and HLECs). Due to the expression of dose of drug treatment, the ADCC test performed better
junction biomarker CD31, slower diffusion rates were in the 3DPF model than in the 3DP model, indicating
seen when these cells were used. Through replicating that Metuzumab-mediated ADVV effects were also

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