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3D-printing and microfluidics
microfluidics has been studied extensively. Numerous was sheared into the discrete volume by another liquid,
mixing strategies have been developed specifically for resulting in a train of droplets in the microfluidic channel.
microfluidics. Designs of microfluidic mixers, both Li et al. used a droplet microfluidic device as the printhead
passive and active, have been incorporated into the to print hydrogels with embedded liquid droplets . The
[64]
extrusion printhead to homogenize multiple bioinks. printhead used the resin to shear the aqueous solution
Serex et al. developed a 3-inlet microfluidic printhead . into droplets. Authors demonstrated the printing of self-
[51]
Materials from the inlets merged in the outlet channel. healing polymer using this approach. When damaged,
Various microfluidic components could be added to the the embedded droplets at the damaged surface released
outlet channel for different purposes. To promote the chemical agents to repair the fracture. Visser et al. also
mixing, a herringbone structure was added to the surface used droplet microfluidics for bioprinting . Instead of
[65]
of the outlet channel. As the materials traveled down the generating droplets in a microfluidic channel, a piezo-
outlet channel, the herringbone induced chaotic mixing actuated dispenser ejected droplets of hydrogel precursor
and homogenized the mixture before extruding it for in the air which later ran into a liquid stream of crosslinker
printing (Figure 4C). Ober et al. studied a propeller- that was also ejected in air. The hydrogel beads generated
based active mixer for the printhead . As materials from by the free-space droplet microfluidic system were used as
[62]
different inlets entered the mixing chamber, the propeller the building block for bioprinting.
efficiently homogenized them in low volumes over a
short timescale. Using this approach, the authors printed 3.3. What is Next for Microfluidics-enabled
a structure with a fluorescent concentration gradient 3D-printing?
obtained by mixing inks at different ratios. The incorporation of microfluidic technology in 3D
Microfluidics also enables a range of unique fluidic
operations, which leads to unique 3D-printing strategies. printing could potentially disrupt the current norm.
Fluidic operations, such as mixing, sorting, and
Microfluidics is well known for its capability of high-
degree parallelization which has been explored for hydrodynamic focusing, can be further explored to
promote the development of new 3D printers or even
high-throughput printing. Hansen et al. developed a hybrid 3D-printing process.
printhead with a multi nozzle array for parallel printing Advances in microfluidics, particularly the
(Figure 4D) . Bioinks were introduced to the printhead
[52]
from a single inlet which bifurcated several times, forming development of new microfluidic modalities, would
up to 64 outlet channels and nozzles. The bifurcating also bring new opportunities to 3D-printing. There are
many types of microfluidic systems in addition to the
microfluidic network ensured that the extrusion rate at all conventional closed-channel microfluidics. In a way,
nozzles was the same. This printhead could significantly
improve the printing speed of tissue engineering scaffolds, 3D-printing is analogous to building construction. The
which usually consisted of a large number of repetitive current extrusion-based bioprinting is equivalent to
structures. Composite materials were often printed with pouring concrete on site. However, buildings could
also be constructed with precast modular blocks so is
multiphase inks composed a liquid-phase resin and solid-
phase particles. Microfluidic components were added 3D-printing. Instead of curing the ink in situ, inks can
to the printhead to pre-condition the multiphase ink for be pre-shaped into standard modular blocks, and the 3D
printing. One such operation was to concentrate the construction is accomplished by moving these modular
particles. Serex et al. added a passive crossflow filter to blocks to designated locations. Take digital microfluidics,
the microfluidic printhead, which removed liquid from for example, digital microfluidics manipulates discrete
the ink as it moved toward the nozzle, leading to a high droplets on an open surface with a large degree of
concentration of particles in the extruded ink . The freedom. It provides an excellent tool to prefabricate
[51]
particle concentration could also be realized with an discrete building blocks as well as a means to remotely
active concentrator. Collino et al. incorporated an acoustic actuate these building blocks. For example, magnetic
wave generator to localize the particles in the microfluidic digital microfluidics manipulates droplets by a magnet
printhead . When particles were localized to the center through the magnetic particles added to the droplet. It has
[63]
of the channel, liquid on both sides was removed by side the ability to move droplets across platforms in 3D with
channels, concentrating the particles to the central channel the assistance of surface modifications. Magnetic digital
for printing. The same strategy was used to distribute microfluidics could be applied to the manipulation of
particles along the print line. Particles with different precast hydrogel blocks for 3D construction.
morphologies would respond differently to the acoustic 4. Conclusion and Future Perspective
wave, hence were localized to different positions along the
microfluidic channel. Droplet microfluidics was a special In this work, we take a critical look at both 3D-printed
type of microfluidic system in which one of the liquids microfluidics and microfluidics-enabled 3D-printing

70 International Journal of Bioprinting (2019)–Volume 5, Issue 2