Page 109 - IJB-9-5

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

cells unable to effectively carry out biological functions. the bone matrix microgel group showed significantly
In order to promote cartilage regeneration, Zhu et al. better rates, numbers, and lengths of vascular formation
developed a microgel composed of hyaluronic acid, PEG, compared to the GelMA group. The bone matrix microgel
and gelatin that is capable of mixing with cartilage cells group formed a stable vascular network on the first
and maintaining cellular phenotype, promoting cellular day, while the GelMA group only formed a relatively
volume expansion and matrix deposition [136] . By injecting stable vascular network on the third day. The number of
the microgel directly into the site of cartilage defects and formations in the bone matrix microgel group was 2.6
reinforcing it through photopolymerization, a scaffold is times that of the GelMA group, and the length was 6.1
formed to support cartilage regeneration. This microgel times that of the GelMA group [141] .
has shown promising results in animal experiments, as
demonstrated through immunohistochemical staining 6.3. Neuronal tissues
that revealed an increased presence of Aggrecan and The construction of neuronal tissue is made difficult and
COL2 within the interstices of the microgel and a matrix complex by the presence of various types of cells, electrical
more closely resembling native cartilage [136] . Flégeau et al. conduction, growth factors, and cell orientation [142,143] .
prepared an enzyme-crosslinked hyaluronic acid microgel The incorporation of ECM-based polymers into ink in
through mechanical crushing, which can be used as a bioink combination with cells provides tissue specificity. Kajtez
for 3D printing to repair cartilage tissue . Its advantage is et al. developed self-healing, annealing particle-ECM
[96]
that the pore size can be adjusted (from 9% to 21%), and (SHAPE) microgel as a biological ink [144] . SHAPE microgels
the microgel containing human ear cartilage cells can form are composed of a viscous polymer (ECM) solution
a stable 3D structure after printing and the printed product (continuous phase, approximately 30% volume fraction)
can develop stably in vitro. GAG, type II collagen, and type and soft water gel (alginate) microgel (discontinuous phase,
I collagen are uniformly and strongly deposited in the approximately 70% volume fraction). These microgels
gaps between the microgel scaffolds, and the mechanical provide not only physical support for high-fidelity
strength of the printed product can reach approximately embedded printing, but also a microenvironment for
200 kPa after 63 days of in vitro cultivation . Chai cellular interaction that supports healthy cellular growth,
[96]
et al. prepared a SilMA/GelMA microgel by mixing low maturation, and activity [144] . Hsu et al. used mechanical
concentrations of GelMA with a certain concentration of disruption to construct a transparent hyaluronic acid
methyl methacrylate silk protein (SilMA). The strength of microgel loaded with human induced pluripotent stem
the SilMA/GelMA microgel was greater than that of pure cell (hiPSC)-derived cortical neurons [145] . The printed
GelMA hydrogel, and it had good biocompatibility, which product of this microgel was able to support the formation
ensured higher cell survival rates. It also demonstrated of well-organized neural and astrocytic cell clusters and
good performance in repairing bone defects. In animal high levels of axonal extension both within and outside the
experiments, the average bone volume/total volume (BV/ scaffold. In comparison, the length of axons in the control
TV) at 2 weeks was 6.98% in the rat calvarial defect model group was three times shorter than that in the microgel.
repair, which was significantly higher than the average BV/ Furthermore, this microgel scaffold supported long-term
TV (4.56%) in the control group [137] . culture of neural stem cells, with the cells proliferating and
differentiating into large and densely packed clusters of
6.2. Vascularized tissues and structures cells after 3 months of cultivation, with the majority being
The vascular system is crucial for the regeneration of most neural cells surrounded by extensively growing axons
damaged tissues, as it facilitates the exchange of nutrients, both within and outside the microgel scaffold, which were
waste, and gases necessary for cell proliferation. Endothelial well-organized and projecting [145] . Microgels have been
cells arranged within the vasculature promote healthy demonstrated to simulate ECM structure to promote
blood flow and the exchange of nutrients with surrounding neural regeneration. Yang et al. further validated this
tissues; therefore, the formation of these structures during conclusion through their study in which they repaired a
vascularization is crucial for guiding tissue growth [138-140] . 10-mm long gap in the sciatic nerve using hyaluronic acid
Parthiban et al. studied the use of a microgel composed microgel [146] .
of methylacrylate-functionalized ECM proteins of bone
cells for 3D-printing vascularized tissues [141] . This microgel 6.4. Organoids
is primarily composed of frozen demineralized and In addition to being used for printing tissue organs,
decellularized bone matrix, which maintains the biological microgel as a biological ink can also be used to simulate
advantages associated with the composition of natural tissue microenvironments, establish organoid models,
ECM and has strong capacity for cell loading and vascular and reconstruct and simulate in vitro 3D environments,
formation. In in vitro experiments for vascular generation, providing new approaches for modeling and disease

Volume 9 Issue 5 (2023) 101 https://doi.org/10.18063/ijb.753