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International Journal of Bioprinting Low-cost quad-extrusion 3D bioprinting system

based hydrogels, as well as different applications such as validation testing toward satisfying the requirements and
vascular constructs. Moreover, the QEH is being modified regulations that render the bioprinter to be compliant
to be able to accommodate syringes with larger volumes for with the current Good Manufacturing Practices (cGMP)
more scaled-up tissue models and organs. Furthermore, as set by federal agencies, such as the U.S. Food and Drug
to enable further capabilities of reliable non-planar 3D Administration (FDA).
bioprinting, a three-axis rotary stage is being designed and
developed. This would render a substrate that can rotate 6. Conclusion
to keep the nozzle orthogonal to the non-planar printing In this work, a low-cost quad-extrusion multi-material
surface of pre-existing or pre-printed structures. bioprinter was initially derived from an off-the-shelf
For more accurate structural outcomes, it is important desktop 3D printer, Creality Ender 3 Pro. The developed
to be able to precisely control the material parameters QEB was designed and fabricated in-house and validated
involved in bioprinting. From a material standpoint, one through several printed structures using two different
main material property to be tuned would be the bioink printing paradigms, namely, IAP and SBP. The novel design
viscosity, which is controlled by the bioink temperature. enables multi-material bioprinting at a very low cost,
The optimum viscosity value can then be transferred to overcoming the issues of affordability and scalability that
other types of bioink material by controlling the bioink currently hamper the present designs as reported in current
temperature. To realize and attain the desired bioink literature. Moreover, the challenges that traditionally
viscosity, an in situ viscosity measurement system is accompany multi-material printing, like nozzle alignment,
currently being developed to allow the determination of calibration, and diminished printing volumes, are
that optimal viscosity value, from which the temperature overcome with the compactness of the bioprinter design
to be set would be known and actively controlled during presented herein. In addition to the latter advantages,
printing. This is being done in conjunction with real-time the QES developed can be transferred to any other open-
image processing and machine learning algorithms to frame desktop 3D printer to render a fully functional
verify the compliance of the printed structures with the bioprinter. Moreover, the bioprinted constructs produced
designed CAD models. This would enable a better flow of under variable process conditions are then characterized
bioink with enhanced structural fidelity. To be sure, due structurally and biologically to verify the geometric fidelity
to the lack of temperature control and different printing of the bioprinted outcomes, as well as cell viability and cell
mechanisms, the QEB would be limited with the range of function within those constructs. This signifies a great step
different materials it can process, including thermoplastics further toward the availability and affordability of additive
and other hard materials that can be used for biological manufacturing for biological applications since the current
applications. techniques and technologies are still complex and at a
very high cost. With the advancement of this QEB, it
Another limitation of multi-material printing is the becomes feasible to extend the reach of such life-changing
interlayer adhesion strength between different material technologies to the general public at an accessible price
interfaces. This may be caused by the different properties point.
and constituents of the different materials. To overcome
such limitations, different design approaches can be Further development to the QEB is under progress to
followed, like the modification of CAD models and include an onboard UV light source attached adjacent to
toolpaths, to account for the weak interfacial adhesion. This the nozzle that allows instant crosslinking, either during
can be done by setting a small inset at the multi-material or after printing. Also, an active heating system that
interfaces to allow stronger bonding and links between the allows precise control of the bioink and support bath (SB)
different bioinks at boundary interfaces. temperatures, in combination with a real-time viscosity
measurement system, is being developed to optimize the
With the aforementioned developments, along with the bioink viscosity that would render the best structural
expansion of the QEH to make it modular and compatible outcomes. Furthermore, a microfluidic nozzle extension
with several extrusion mechanisms, the scalability of the to the present QEH is being designed to allow the micro-
QEB would become possible with the added attributes mixing of the different materials that are amenable to render
such as increased reliability, robustness, and versatility. new bioinks with different combinations or gradients
This would facilitate significant contributions to various from the separate four bioinks. The QEB with these low-
engineered tissue applications that are currently out of cost upgrades would even further expand the range of
the reach of current bioprinting capabilities. Moreover, applications that can be achieved with such an affordable
in order to translate bioprinting studies into clinical use, and capable extrusion system, with high reliability and
it will be necessary to ensure process reliability with repeatability.

Volume 10 Issue 1 (2024) 308 https://doi.org/10.36922/ijb.0159