Page 96 - IJB-9-5

International Journal of Bioprinting Application and prospects of 3D printable microgels

2.4. Electrospray between adjacent microgels are negligible. As a result,
The basic principle of the electrospray method is to establish jammed microgels exhibit viscous fluid-like behavior
an electric field between the metal needle and the receiving under shear stress and recover to a viscoelastic solid
device, which enables the droplets to overcome the surface upon release of external load. When the particle volume
tension and be sprayed into the receiving device. After fraction of microgel is between 0.58 and 0.74, jammed
crosslinking, microgels are formed. The particle size of the microgel display excellent shear thinning and self-
microgels depends on the applied voltage, needle diameter, healing properties [60] . The flow and recovery properties
and flow rate . This method can produce microgels of this responsive pressure approach fulfill the design
[54]
with extremely small diameter (as small as 1 μm), but requirements for 3D bioprinting ink, allowing for the
the dispersion of hydrogel microparticle suspensions is theoretical possibility of printing microgels with any
poor . The electrospray method is less commonly used in constituent composition based on this strategy [61] .
[55]
the production of microgels. Through the process of gravity packing, Highley et al.
2.5. Mechanical fragmentation prepared a microgel (NorHA) using norbornene-modified
[61]
Mechanical fragmentation is a method of breaking down hyaluronic acid, PEGDA, and agarose . The NorHA
already formed hydrogel into microgel through physical microgel was prepared using a microfluidic device and
means, such as using a fine wire mesh for forced mechanical had a diameter of approximately 100 μm. It exhibited good
fragmentation of the hydrogel , or using a rotary stirrer rheological properties upon jamming, with its viscosity
[56]
to break down crosslinked hydrogel into hydrogel– decreasing with increasing shear rate and shear yield
microgel . Mechanical fragmentation has an extremely increasing with strain. It also displayed the ability to flow
[57]
high yield of microgel, but it is unable to accurately control during extrusion and rapidly stabilize upon sedimentation
the shape and size of microgel . In 3D bioprinting, the (Figure 1B–D). NorHA microgel can be printed layer
[27]
batch emulsification and mechanical fragmentation by layer through the use of an extruder, resulting in
methods are widely used due to their simplicity and fast structures with short-term stability. Through post-printing
production speed. photopolymerization, the compressive modulus of the
printed structures is further enhanced, allowing for long-
3. Strategies for assembling microgels term stability. In addition to layer-by-layer printing, these
microgels can also be used as bioinks for 3D-printing
To prepare for 3D bioprinting, it is necessary to process solid structures. One of the most important evaluation
the obtained microgel into printable microgel. The self- criteria for bioinks used in 3D bioprinting is the viability of
assembly of these microgels can be facilitated through encapsulated cells, and NorHA microgels have been shown
interparticle interactions, and the assembly strategies can to maintain cell viability at around 70% after encapsulation
be categorized based on the strength of these interactions. prior to printing .
[61]
This classification system allows for a more efficient and
targeted approach to the self-assembly process, thereby 3.2. Chemical effect
improving the overall success of the 3D bioprinting The assembly of microgels can be induced through
process. The advantages and disadvantages of the microgel chemical interactions, including enzyme catalysis,
assembly strategy are summarized in Table 2. photopolymerization, click chemistry, and amine coupling
reactions (Figure 2A), which typically involve the
3.1. Gravity irreversible formation of covalent bonds .
[62]
Gravity packing is the most commonly used method
to “jam” the microgel as a bioink (Figure 1A) [28] . In the Enzyme catalysis refers to a chemical reaction that
“jammed” state, the particles within the microgel move is catalyzed by an enzyme . Currently, the enzymes
[63]
as a cohesive whole, resulting in the material behaving reported to be used in microgel assembly are primarily
as a solid at the macroscopic level until sufficient force transglutaminases. Song et al. developed a microgel
is applied to cause movement [27,58,59] . The mechanism mediated by transglutaminase, which is composed of a
behind this occurrence is that as the concentration discrete phase (enzyme-crosslinked gelatin microgel)
of microgel increases, the interparticle friction also and a crosslinkable continuous gelatin precursor solution
increases, leading to deformation of the microgel under containing transglutaminase. This microgel has good
external force. It is typically observed that a transition injectability and cell loading activity . The enzyme-
[64]
from hydrogel particle blockage occurs when the mediated microgel assembly process is typically carried
volume fraction of the microgel reaches approximately out under mild conditions (neutral pH and moderate
0.58 [32] . The jamming of microgel is mainly influenced temperature), allowing for the incorporation of live cells
by frictional forces, and the van der Waals forces into dynamically formed microgel assemblies .
[28]

Volume 9 Issue 5 (2023) 88 https://doi.org/10.18063/ijb.753