Page 100 - IJB-9-5

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

and easy, but due to the lack of strong charges between unstable and prone to structural instability or even collapse
the assembled microgels, this interaction is weakened in upon removal of the external forces [28,76] .
electrolyte solutions. Fluidic forces are commonly used to assemble polymer

The assembly of microgels can also be achieved through precursors into microgel through the application of
the interaction of multiple hydrogen bonds, although external forces on a one- or two-dimensional microfluidic
the effect of individual hydrogen bonds is relatively channel device, ultimately resulting in the formation of
weak. However, the microgels formed by the action of a the microgel at the outlet of the device . This assembly
[77]
large number of hydrogen bonds have high mechanical method has the advantage of precise control over the
strength. For example, the number of hydrogen bonds in assembly process, allowing for the design of specific shapes
the microgels that are made by mixing chitosan methyl for the microgel. Surface tension is utilized in the assembly
acrylate and polyvinyl alcohol (PVA) after repeated of microgel, with microgel solutions in an oil or gas phase
freezing and thawing increase, thereby greatly enhancing being closely stacked due to the surface tension at the
its mechanical strength [36,73] . liquid–liquid or liquid–gas interface, and completed upon
the removal of the oil or liquid phase. This method is quick
The biomolecule-chain melanin affinity interaction
is one of the strongest non-covalent interactions. The and simple, but the assembled microgels are not stable and
the size of the assembled microgels cannot be accurately
microgels assembled through this interaction are extremely controlled [78-80] .
stable, but at the same time, this binding interaction is
irreversible. Hu et al. used microfluidic technology to Under the influence of an external magnetic field,
prepare biomolecule-functionalized alginate microgel. By microgels containing magnetic nanomicrogels are capable
incubating the biomolecule-functionalized microgel with of assembly, and the assembly of the microgels can be
soluble chain melanin affinity protein for a short period of controlled through the design of devices with different
time (about 5 min), microgels can be assembled . shapes and the adjustment of the intensity of the external
[74]
magnetic field. Currently, there is also a method for
3.4. Cell–cell junction assembling 3D-shaped microgels (including multilayer
Self-assembly of hydrogel–microgel can be achieved cylindrical and spherical structures). This method is fast in
through intercellular interactions such as cell–cell or cell– assembling microgels and is able to prepare complex and
matrix adhesion. In other words, cells are cultured on precise 3D-structured microgels; however, the cytotoxicity
the surface of hydrogel–microgel, and the binding forces of the magnetic nanomicrogels limits their use in tissue
between cells drive the assembly of the hydrogel–microgel engineering [81,82] . Microgels can also be assembled through
(Figure 2C). For example, Matsunaga et al. cultivated an external acoustic field, in a way similar to the driving
cells on the surface of single dispersed collagen hydrogel– force of a magnetic field. When the suspended microgels
microgel, and then stacked the cell-coated hydrogel– are subjected to an external sound wave, they can be
microgel in a mold to trigger intercellular interactions and assembled into single- or multi-layer structures. However,
assemble it into a hydrogel . This assembly method can microgel structures assembled solely through the action of
[75]
reconstruct 3D tissue with uniform cell density . The sound waves are typically unstable and require secondary
[75]
self-driven forces of cells spontaneously drive the assembly crosslinking for stable structure .
[83]
of microgel in this manner, without the involvement of
external factors, resulting in excellent biocompatibility of 4. Characteristics of microgels
the assembled microgel. However, several challenges are
faced in this assembly process, including the requirement 4.1. Biological properties of microgels
for microgels with a certain degree of cell adhesion Bioink is defined as a cellular formulation, potentially
ability on their surface, and the need for microgels that containing bioactive components and biomaterials,
are conducive to cell proliferation and migration, with that is suitable for processing through automated
[84]
sufficient cell growth speed to maintain efficiency in the biomanufacturing techniques . In terms of function,
assembly process. an ideal bioink must be able to be printed through
bioprinting technology, maintain cellular viability, and
3.5. External driving force trigger the desired cellular response [85,86] . The biological
Common external driving forces for the assembly of characteristics and biocompatibility of microgels are
[10]
microgel include fluid forces, surface tension, magnetic crucial for the realization of 3D bioprinting . Microgels
forces, and acoustic forces (Figure 2D). The rapid assembly must be able to maintain the health and vitality of cells
of microgel can be achieved through the use of external during the process of bioprinting, and protect cells during
driving forces, but the resulting structures tend to be the process of bioprinting. For ordinary hydrogels, the

Volume 9 Issue 5 (2023) 92 https://doi.org/10.18063/ijb.753