Page 104 - IJB-9-5

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

disperse microgels required larger nozzles (410–610 μm) may hinder cell diffusion and migration, and high pressure
to print smoothly. For a monodisperse microgel, smaller or shear forces may cause cell damage and/or death [103-105] .
nozzle sizes (200 μm) are able to produce 3D structures Microgels used as bioinks for direct writing can effectively
with higher finesse than larger nozzle sizes (250 μm). In overcome these limitations. The performance of microgels
order to study the effect of the stiffness of water-based prepared by different preparation and assembly strategies
microgel on the printing process, three microgels (PEG5, also varies in direct bioink writing.
PEG10, and PEG20) were constructed, with Young’s moduli 5.1. Improvement of the geometric structure of
of 30–40 kPa, 20 kPa, and 10 kPa, respectively. When microgels
subjected to the same pressure (15 μN) during the printing
process, the PEG20 microgel showed greater deformability. Generally, mechanical fragmentation method involves
The stacking of cylindrical prints was performed without the physical fragmentation of pre-formed hydrogels to
secondary crosslinking, with stack heights of 20 mm, produce microgel. For example, crosslinked hydrogels
10 mm, and 5 mm for the three respective microgels. After can be mechanically forced through a fine steel mesh to
form smaller microgel, with the size of the microgel being
the cells were packaged and printed for three days, the controlled by altering the aperture shape and size of the steel
viability of cells within the microgel was approximately
90%, 90%, and 40%, respectively. The increased stiffness of mesh. The main advantages of mechanical fragmentation
hydrogel microspheres improved mechanical strength, but methods are their speed and simplicity, with the simple
may also potentially affect cellular activity [33,59,99] . process being able to rapidly generate a large amount of
micromicrogel. However, the disadvantage is that the
shape and size of the generated microgel are difficult to
5. Current progress of developing accurately control, which justifies the limited number of
microgels as bioinks in extrusion-based reports concerning its performance in 3D bioprinting in
3D bioprinting the past decades .
[27]
Over the past decade, various 3D bioprinting strategies Flégeau et al. reported a microgel suitable for 3D
with distinct characteristics have been developed. bioprinting made from tyramine-modified hyaluronic acid,
Currently, the mainstream strategies include inkjet which was obtained through mechanical fragmentation
bioprinting, stereolithography, laser-assisted bioprinting, and enzymatically crosslinked through the addition of
[96]
electrospinning-based bioprinting, and extrusion-based horseradish peroxidase and hydrogen peroxide . The gel
bioprinting . Extrusion-based 3D bioprinting is one was then screened through metal grids with pore sizes of
[10]
of the most common printing methods, mainly due to 40, 100, and 500 µm, resulting in a microgel with tyramine
several advantages of extrusion-based bioprinting over residues that could undergo secondary crosslinking to
other methods, including (i) the ability to use a variety of stabilize the scaffold (Figure 4A and B). The product of the
bioinks to create tissue structures; (ii) the manufactured secondary crosslinking was found to fully degrade after
structure having physiologically relevant cell density; soaking in hyaluronic acidase for 20 days and demonstrated
(iii) the relatively low cell damage during the bioprinting excellent stability with no swelling in phosphate-buffered
process; (iv) the ability to create scalable structures with saline (PBS) for 21 consecutive days. After sieving, all the
anatomically precise geometries; and (v) being relatively microgels displayed shear-thinning behavior, with the
low-cost. Its main drawbacks are as follows: (i) it can yield stress of approximately 139 Pa for microgels of all
damage cells during the extrusion process; and (ii) the sizes, which were capable of being printed, but the use of 40
resolution of the printed product is relatively low and μm-sized microgel resulted in higher-resolution products
the feature size is limited. The application of microgels (Figure 4C). Cells also displayed good viability in microgels
is expected to address these issues, and therefore, in this produced through mechanical fragmentation, with cell
section, we mainly focus on the research progress of viability at 75.7 ± 8.2%, 73.1 ± 9.4%, and 70.2 ± 9.0% on
microgels in this type of printing strategy [100,101] . day 1 for 40, 100, and 500 µm-sized microgel products,
respectively, and maintained high viability at 94.5 ± 4.7%,
Direct bioink writing refers to the direct extrusion of 93.4 ± 1.3%, and 94.1 ± 4.6% on day 21, respectively. The
bioinks with rheological properties to form a predetermined research of Flégeau et al. demonstrates that microgels
shape and configuration at a designated location. During produced through mechanical fragmentation possess
the extrusion process, the bioink behaves like a fluid and good cell compatibility and printing characteristics, and
then transforms into a solid state upon extrusion [102] . The the preparation method is simple and quick .
[96]
advantages of direct bioink writing lie in its simplicity
and high repeatability. However, when using traditional Kessel et al. utilized HA-MA as the raw material and
hydrogels as bioinks, dense gels and/or other components constructed a class of entangled microfiber-based large-

Volume 9 Issue 5 (2023) 96 https://doi.org/10.18063/ijb.753