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3D-printed bioreactors for in vitro modeling and analysis
provided opportunities to investigate the tissue mechanisms of the metastasis of breast cancer
physiology and the role of each tissue in the cells to bone marrow . In the study, transparent
[40]
pathogenesis of osteoarthritis. PDMS chambers for cell growth casted from a
3D-printed mold (Rostock MAX V2 Desktop
2.1.4 3D-printed bioreactor for testing of printer) were separated from the media reservoir
therapeutics
by a membrane. 3D-printing of this geometrical
3D-printed bioreactors are also useful in the clinical design enabled frequent monitoring of interactions
translation and commercialization of standardized between cancer cells and the bone matrix in vitro
cell-based products for cell-based therapies and drug- and eliminated the need to take bone metastasis
testing. A reusable material jetted (Objet Connex 350) samples from patients.
fluidic device incorporated a porous polycarbonate Another study demonstrated the use of a
membrane not only enabled molecular transport and perfusion-type liver organoid model using a
drug migration through the membrane (Figure 1B sinusoidal liver lobule on a chip 3D-printed by SLA
and C) but also indicated drug susceptibility of (Cellbricks bioprinter) with polyethylene glycol
mammalian cells . Moreover, collecting analytes and gelatin containing bio-inks . Cells cultured
[34]
[37]
while simultaneously measuring the release stimulus within the liver organoid model revealed high-
was also possible with this 3D-printed bioreactor . yield protein expression compared to monolayer
[13]
Electrodes and other additional functionalities cultures. This in vitro model in 3D-printed
such as membrane inserts and fluidic interconnects bioreactor ensured hepatocyte functionality and
were integrated to ensure signal detection and flow could be modified to accommodate nutritional
control. A compact ready-to-use material extruded supply for larger tissue models to explore the
(MakerBot Replicator 2X) cartridge containing assay mechanistic properties. The organ-on-a-chip
reagents was integrated with genetically engineered systems could also be personalized by integrating
sentinel cells and interfaced with a custom-developed additional systems to emulate the complexities of
smartphone Tox-App for rapid quantification of an organ. To design a 3D arterial thrombosis model,
cellular toxicity . anatomical models were obtained from imaging
[35]
scans and converted into a printable 3D model.
2.1.5 3D-printed bioreactor for organ-on-chip The molds for chips with miniaturized healthy
applications
and stenotic vasculatures were then developed
An organ-on-a-chip device fabricated by 3D- using a Perfactory 3 SLA 3D-printer with PIC100
printing aims to assemble organ models in 3D resin. The vascular structures incorporated on-
specific architecture on a microfluidic chip. By chip successfully mimicked vessel environments,
virtue of precise geometrical features attained by showing human blood flow at physiologically
3D-printing coupled with controlled flow dynamics relevant conditions and with artificially induced
and imaging compatibility of microfluidics, a thrombosis . Another system non-invasively
[38]
continuous perfusion model had been developed interfaced a 3D-printed microfluidic device with
to imitate the blood-brain barrier environment . a porcine kidney model to isolate and profile
[36]
This setup consisted of a porous membrane that biomarkers from whole organs in real-time. From
allowed coculture of different cell types across the the cortex of the kidney, relevant metabolic and
membrane and a 3D-printed cell insert module pathophysiological biomarkers were transported
that accommodated cell monolayers which formed to the microfluidic device by virtue of the fluid
a fully functional closed-loop perfusion model. flow in the microchannel. Hence, the 3D organ-
This 3D-printed bioreactor was able to overcome on-a-chip could perhaps overcome the drawbacks
the limitations faced by static culture models and of whole organ structures . For a complex organ
[41]
demonstrated the synergy between microfluidics model, a multi-channel perfusion-type chamber
and 3D-printing . Similarly, a 3D bone-on-a-chip was developed to assess endocrine secretions,
[47]
device used coculture strategies to study disease due to their multiple inlet and outlet needs . The
[39]
86 International Journal of Bioprinting (2020)–Volume 6, Issue 4