Page 102 - IJB-9-5

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

ability than ordinary hydrogels. On the fifth day of using fraction increases, the friction between microgels
the microgel, hair follicles and sebaceous glands appeared increases, causing the microgels to become more “solid”
in the wound, almost achieving tissue regeneration . in a blocked state. Theoretically, when the accumulation
[63]
Hyaluronic acid-based microgels have demonstrated the fraction reaches 0.64, single dispersed microgel can reach
ability to facilitate the migration of neural stem cells toward the maximum blocked state under random configuration.
wounds and the formation of blood vessels, exhibiting good When the accumulation fraction reaches 0.74, perfect
tissue remodeling capabilities. This suggests a potentially accumulation can be achieved. In the state of particle
significant application in the context of irregular spinal accumulation, the microgel exhibits shear thinning and
injuries . The modified heparin chitosan microgel self-healing characteristics. Studies have reported that
[90]
were found to effectively repair bone defects in type II tyramine-modified hyaluronic acid microgel (particle
diabetes rat models while also improving the immune diameters of 40, 100, and 500 µm) have similar yield stress
microenvironment . It has been consistently found in (139 Pa). In repeated cycles at low (1%) and high (500%)
[91]
these studies that the unique pore size of micromicrogel strain, all bioinks transition from solid (G′ > G″) to liquid-
plays a crucial role in improving cellular responses. like (G″ > G′) under high shear stress. In low shear mode,
The most notable biological characteristic of microgels all bioinks exhibit excellent shear recovery performance,
is their microscale pore network, which closely mimics with the initial storage modulus reaching 100%. There is
the microenvironment for cell survival. Compared to a significant negative correlation between elastic modulus
traditional hydrogels, microgels are more conducive and pore diameter, with E = 9.9 ± 3.6, 7.5 ± 2.4, and 5.7 ±
to cellular behaviors such as growth, proliferation, 2.2 kPa when the pore diameter is 40, 100, and 500 µm,
differentiation, and migration. According to extensive respectively. This microgel exhibits excellent printability,
research comparisons, the principle behind this may be enabling the 3D bioprinting of cells with the ability to
that the interconnected micropores and void spaces not strengthen the printed structure through post-print
[96]
only facilitate the transport of nutrients, thereby increasing crosslinking (Figure 4B and C) . Microgels are not limited
cell vitality, but also promote cell infiltration and vascular to spherical microgels, as hydrogels with high aspect ratios
formation without having to wait for hydrogel degradation. (hydrogels) can also form microgels. Kessel et al. reported
In addition to the above, microgels also exhibit excellent a “microchain” microgel based on hyaluronic acid-methyl
encapsulation properties, as they can modify the microscale acrylate (HA-MA), with a microchain diameter of 40–
features such as particle size and shape of microgels 100 µm and a microgel porosity ranging from 7.4 ± 0.9%
[97]
to adjust the release profile of growth factors or drugs. to 2.0 ± 0.8% . The yield stress of the microgel changes
Meanwhile, microgel heterogeneity allows multiple release with the degree of crosslinking and the diameter of the
profiles and degradation behaviors of growth factors or microchain, with higher crosslinking resulting in lower
drugs to be incorporated into a single printing process, yield stress and larger microchain diameters resulting in
which is advantageous for many tissue repair strategies to higher yield stress. Shear recovery was found to be the best
match the multi-level biological signaling [63,92,93] . in microgel with moderate crosslinking, at approximately
82%, while the highest crosslinked microgel had a shear
recovery of around 70% and the lowest crosslinked microgel
4.2. Mechanical properties of microgels had a shear recovery of around 20%. This microgel exhibits
As a bioink, microgel possesses excellent shear viscoelastic good cell loading ability, enabling the loading of cells prior
capabilities, allowing it to be extruded through a printing to microgel assembly or post-assembly (Figure 4E) .
[97]
head while protecting encapsulated cells from damage
due to high shear forces. The elegance of using microgel The mechanical strength of microgel is also a critical
for 3D printing lies in the smooth transition between factor in achieving 3D bioprinting. After 21 days of printing,
the fluid and the solid states [94,95] . This transformation is the elastic moduli of tyramine-modified hyaluronic acid
highly related to the structural characteristics of microgel, microgel with pore sizes of 40 µm, 100 µm, and 500 µm were
which differ from hydrogels in that they are composed of 103.6 ± 18.5, 83.9 ± 19.7, and 78.1 ± 19.2 kPa, respectively,
micrometer-sized hydrogel–microgel within their interior. while the elastic modulus of the control group was 58.3 ±
The interaction between these micromicrogels results in 30.2 kPa. After 63 days, the elastic moduli of microgel with
the microgel exhibiting solid-like behavior but becoming pore sizes of 40 µm, 100 µm, and 500 µm were 145.3 ±
liquid-like under the influence of external stress. Therefore, 22.3, 201.6 ± 8.9, and 152.6 ± 47.2 kPa, respectively,
the porosity and hardness of the micromicrogel largely while the elastic modulus of the control group decreased
determine the mechanical properties of the microgel . to 33.7 ± 17.2 kPa (Figure 4C) . Yang et al. reported on
[96]
[60]
When the accumulation fraction of microgel reaches 0.58, a PAAm/PAMPS microgel based on a resilient particle
the microgel exhibits as solid state. As the accumulation double network (P-DN) hydrogel, which possesses two

Volume 9 Issue 5 (2023) 94 https://doi.org/10.18063/ijb.753