Page 94 - IJB-9-5

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

can be used for this strategy have a limited range of viscosity networks with single-component hydrogels to enhance the
(3.5–12 mPa·s) [5,6,12] . Laser-assisted bioprinting strategy various properties of single-component hydrogels.
allows for the application of bioinks with a wider range of In order to address the shortcomings of gels as bioinks,
viscosity (1–300 mPa·s) and can print products with high many efforts have been made to improve gels by adding
resolution and high cell viability. However, this technology nanoparticles or using multi-component gels as bioinks.
is relatively immature and costly [7,13-15] . Electrospinning While this has resulted in improved properties in the
strategy allows for continuous or discontinuous 3D printed products, these bioinks are still not widely used
bioprinting, but fails to print products evenly owing to in 3D bioprinting due to their complex design and poor
the charged jet stream [8,16-18] . Compared to the above 3D generalizability [25,29-31] .
bioprinting strategies, extrusion-based printing strategy
has several advantages: (i) it can print using bioinks with In order to address the challenges of traditional
a wider range of viscosity (30 mPa·s to >6 × 10 mPa·s); hydrogels as bioink in 3D bioprinting, many researchers
7
(ii) it can produce constructs with higher cell density (>10 have turned their attention to a new emerging bioink
8
cells/mL to cell spheroids); (iii) it can continuously extrude called microgel. Microgels are water-based microgels
bioinks (making it easier to build products with good with diameters in the micrometer range that are
integrity); and (iv) it has a relatively simple instrument assembled in a manner similar to hydrogels through
system that is easy to operate. However, extrusion-based processes such as dense packing or jamming. Because the
printing is limited by its slow printing speed and extrusion physical interactions between particles are weaker than
that causes a reduced cell viability [9,10,19-21] . the covalent bond interactions within particles, microgel
can still yield to flow when external forces overcome
Bioink is one of the most important factors in achieving interparticle friction during printing, while the physical
successful 3D bioprinting, as it almost determines the interactions between particles are restored after printing,
effectiveness of 3D bioprinting in constructing engineered allowing the printed structure to maintain integrity.
tissues and organs [22,23] . For 3D bioprinting, bioink needs to Thanks to the covalent bond interactions within the
possess both mechanical and biological properties. These particles, microgels remain intact throughout the process
ensure that the bioink can print stable, intact 3D structures and protect encapsulated cells from damage caused by
while ensuring that the printed structures can support high shear stresses, further improving the stability of
cell adhesion and proliferation . Gel-based bioinks 3D bioprinting [32,33] . Microgels have been reported to
[24]
are the most widely used materials in 3D bioprinting. be compatible with a variety of material formulations,
Currently, there are various gel-based bioinks used in including hyaluronic acid, agarose, PEG, chitosan,
3D bioprinting, including alginate, fibrinogen, gelatin, and gelatin. Additionally, their mechanical properties
collagen, chitosan, hyaluronic acid, methacrylated gelatin and stretchability can be improved through secondary
(GelMA), polyethylene glycol (PEG) and decellularized crosslinking strategies .
[33]
extracellular matrix (dECM) [10,23,25,26] . Both natural and
synthetic single-component gels have certain limitations. Due to their unique dynamic structure, excellent
Traditional hydrogels are crosslinked to form a continuous biocompatibility, and adjustable mechanical properties,
volume (bulk hydrogel), with external dimensions equal to microgels are emerging as a new star player in the field of
or greater than millimeter scale, and internal pores at the 3D bioprinting and have a huge potential in the biomedical
nanometer scale. As a result, the limitations of traditional field. In this review, we briefly introduce the characteristics
hydrogels as bioinks mainly lie in their inferior printing and preparation strategies of microgel. Then, we focus
resolution and cell culture activity compared to microgel. on the use of microgels to construct 3D objects in the
The size of microgel is in the micrometer range, which is biomedical field. Finally, we summarize the challenges
conducive for injection or printing and enable printing of faced and discuss how to further utilize these microgels for
smaller constructs. Moreover, the internal pores or gaps 3D bioprinting.
within microgel are also in the micrometer range, which 2. Strategies for preparing microgels
is favorable for cell growth and biological behavior such as
proliferation, differentiation, and migration. Additionally, Hydrogels possess high water content and characteristics
the unique rheological properties of microgel can protect similar to extracellular matrix, which are the attributes
encapsulated cells from shear forces during the printing leading to their widespread use in the field of 3D
process [10,22,27,28] . On the other hand, the heterogeneity of bioprinting. Hydrogels form polymer networks through
microgels enables it to realize multi-layered and multi- physical or chemical crosslinking, with internal pore sizes
component 3D structures in a single print. Microgels can at the nanoscale level. This limits their biocompatibility
also act as rigid hydrogel networks and form reciprocal as a bioink and hinders cell adhesion, migration, and

Volume 9 Issue 5 (2023) 86 https://doi.org/10.18063/ijb.753