Page 185 - IJB-9-2

International Journal of Bioprinting A regulated GelMA-MSCs scaffold by three-dimensional bioprinting

degeneration or arthritic manifestations with pain and differentiation, apoptosis, and disease progression . As
[16]
disability . small molecule inhibitors of endogenous gene expression,
[4]
Cartilage tissue engineering has made significant microRNAs play a key role in stem cell migration,
progress in the past two decades, but tissue engineering proliferation, and differentiation. Although the research
structures generally cannot regulate cytokines and spatial on microRNAs is still in its infancy, microRNAs may be
structure of tissues and cannot directionally regulate as important as transcription factors in regulating gene
[5]
[17]
expression in advanced eukaryotes . Various microRNAs
cells to perform the required biological behaviors. Cells play important roles in the development of chondrogenic
play an important role in the repair of OA cartilage. [18]
How to regulate cells to play a corresponding role in the differentiation and may serve as potential biomarkers .
process of pathological repair has become a research Some studies indicated that miR-30a, miR-488, miR-
hotspot. However, the emergence of three-dimensional 221, and miR-410 regulate chondrogenic differentiation
[19]
(3D) bioprinting technology provides a new approach processes . In the study of OA, Zhang et al. found that
for the treatment of cartilage damage. 3D bioprinting is microRNA-410 targets the pseudo binding site in the
a combination of 3D printing and tissue engineering. It 3’-UTR of Wnt3a gene, thereby regulating the Wnt signaling
pathway . The level of Wnt3a in OA patients varies with
[20]
constructs biological models with cells, regulatory factors, the increase of inflammation severity and was significantly
and biological materials as structural units . The 3D negatively correlated with the level of microRNA-410 .
[6]
[20]
bioprinting of artificial cartilage is mainly studied in three The study pointed out that microRNA-410 can promote
aspects: (i) scaffold material, (ii) seed cells, and (iii) in vitro
simulation of the growth environment and mechanical the chondrogenic differentiation of MSCs during TGF-
environment in vitro . This technology uses scaffolds β3 induction. The main mechanism is that the expression
[7]
of degradable and highly biocompatible materials to of microRNA-410 negatively regulates its target gene
Wnt3a and inhibits the Wnt signaling pathway during
combine cells with scaffolds in vitro. By simulating natural cartilage differentiation. MicroRNA-410 can significantly
extracellular matrix and adding bioactive factors for accelerate β-catenin nuclear translocation and binding
mechanical and chemical induction of cells, stimulating with the promoters of b-FGF, IGF-1, and TGF-β1.
cell growth, proliferation, differentiation, and formation The results suggest that microRNA-410 has a specific
of cartilage-like tissue can thereby replace damaged function to regulate expression of genes associated with
cartilage .
[8]
chondrogenesis in response to TGF-β3. However, this
Due to the addition of cell regulatory factors, study lacks further validation and confirmation in vivo .
[21]
3D bioprinting has higher requirements for scaffold Some studies have verified that microRNA-410-3p can
environment and biocompatibility than tissue engineering. directly target the HMGB1 gene to regulate chondrocyte
Hydrogel has excellent biocompatibility and is considered apoptosis and inflammatory response . MicroRNA-410
[22]
a suitable material in the development of 3D bioprinting played a regulatory function in cartilage differentiation
scaffolds . Therefore, gelatin methacryloyl (GelMA) is a and subchondral bone remodeling through the Wnt
[9]
double bond-modified hydrogel, which can be cross-linked signaling pathway. The primary mechanism of action was
and solidified into a gel under ultraviolet (UV) light , the formation of a functionally active regulatory interface
[10]
and has been proven to be an ideal scaffold material for in the cartilage and adjacent subchondral bone . When
[23]
cartilage repair in the previous studies [11-13] . MSCs differentiate into chondrocytes in vitro, they
The further application of GelMA in combination with become integrated cell clusters, and their migration and
stem cells alone is limited due to the lack of factors, such as proliferation abilities are greatly reduced. After GelMA
cell regulatory behavior and migration. Some studies have was implanted, its migration and proliferation capacity was
shown that the addition of bone morphogenetic protein poor, and it was unable to transport type II collagen and
4 into GelMA can promote macrophage polarization other substances in chondrocytes to various parts of the
and bone defect repair . Therefore, it is necessary to defect. So far, the studies on the effect of microRNA-410 on
[14]
add some functional factors, such as regulation of cell chondrogenic differentiation of MSCs have only focused
[24]
behavior, migration, proliferation, and differentiation into on the 2D cell culture , and the research on cartilage
mesenchymal stem cells (MSCs) . MicroRNAs belong repair in vivo is still lacking.
[15]
to a group of non-coding RNAs encoded by the genome When the osteochondral defect is transplanted in vivo
with a length of about 20 – 23 nucleotides, which can affect by 3D bioprinting technology, the stem cells in the bioinks
the degradation of mRNAs or hinder their translation by will realize the physiological function of multifunctional
guiding the silencing complex (RISC) of the target gene differentiation depending on the microenvironment. When
microRNA base pair, so as to regulate cell proliferation, the regulatory factors are added, the biological behavior

Volume 9 Issue 2 (2023) 177 https://doi.org/10.18063/ijb.v9i2.662