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International Journal of Bioprinting 3D-Printed GelMA biomaterials in cartilage repair

subchondral regeneration. These scaffolds demonstrated PRP hydrogel with the ideal mechanical strength and
potential therapeutic applications in the treatment of full- sustained release of PRP that benefited the growth and
thick articular cartilage defects, with implanted scaffolds differentiation of ATDC5 cells. Based on this finding,
even leading to the recovery of rat gait behavior. they further developed an osteochondral mimetic scaffold
These bioprinted constructs supported chondrogenesis by gradually printing bioinks composed of the adipose-
[51]
and cartilage-specific ECM deposition by continuously derived stem cells (ADSCs), PRP, and GelMA . These
releasing TGF-β, indicating the potential of ink with hydrogels had relatively slow degradation rates, high
TGF-β3 for a “single-stage” or “point-of-care” approach for mechanical properties, and tissue-specific biomimetic
cartilage healing. Despite that TGF-β plays a vital role in structures, promoting in vitro osteochondral tissue
chondrogenesis and cartilage formation and regeneration, formation, including hyaline and hypertrophic cartilage
it has been observed that increased levels of TGF-β1 are and bone phases. One of the advantages of PRP over other
present in the animal models of osteoarthritis , and this growth factors is its patient- and tissue-specific properties,
[42]
active form of TGF-β1 could lead to changes in the joint suggesting that PRP application could contribute to future
tissue that contribute to the development and progression personalized 3D printing.
of osteoarthritis . Furthermore, TGF-β1 can also Overall, the combination of 3D bioprinting and
[43]
stimulate the production of pro-inflammatory cytokines GelMA hydrogels in regenerative medicine showed a
and chemokines, which contribute to the inflammatory huge potential in the creation of anatomically complex
response observed in osteoarthritis. This further exacerbates articular cartilage tissue substitutes. While some of the
the degenerative changes in the joint tissue. Therefore, these growth factors mentioned above have been incorporated
disadvantages should be considered in the fabrication of into GelMA for cartilage regeneration, these studies have
constructs using both 3D printing or traditional techniques. only included one growth factor in the scaffolds. However,
articular cartilage is a complex tissue with three layers,
5.1.2. Anti-inflammatory growth factors and 3D printing technology has the potential to enable
To mitigate the effects of inflammation and facilitate the construction of multi-layered scaffolds with different
cartilage regeneration in conditions such as osteoarthritis, growth factors on each layer to achieve high-fidelity tissue
inks have been supplemented with anti-inflammatory repair. Therefore, constructs with multi-layer and multi-
factors. For example, Lin et al. developed a bilayer factors are expected in order to facilitate the regeneration
[44]
scaffold using GelMA combined with interleukin-4 of articular cartilage.
(IL-4) and PCL, as well as PCL-HA, which successfully
demonstrated anti-inflammatory effects. The scaffold’s 5.2. Cells
composition was similar to that of native tissue, leading to GelMA has many desirable properties, such as
improved cartilage and subchondral bone formation. biocompatibility and controlled degradability, and these

5.1.3. Platelet-rich plasma properties make GelMA an attractive option in cartilage
Platelet-rich plasma (PRP) is an emergent therapeutic tissue engineering and regenerative medicine applications
strategy in biomedical applications that has demonstrated where it can help promote the proliferation, migration,
positive effects in enhancing cartilage injury healing . and differentiation of chondrocytes and stem cells, and
[45]
PRP is a mixture of growth factors that are essential for thus facilitate the formation of new functional cartilage.
tissue healing, such as platelet-derived growth factor, Researchers also emphasized the importance of utilizing
vascular endothelial cell growth factor, TGF-β, fibroblast additional seed cells in hydrogel-based cartilage treatment.
[52]
growth factor, and insulin growth factor . In clinical In a study by Zheng et al. , a GelMA with silk fibroin
[46]
practice, PRP is used to alleviate pain and inflammation, (SF) hydrogel was developed, and this GelMA-SF hydrogel
promote neocartilage formation, and facilitate functional could facilitate chondrogenesis of BMSCs in vitro. Notably,
recovery in knee and hip joints . Moreover, PRP has they observed that BMSCs-seeded hydrogels resulted in
[47]
been shown to guide stem cell differentiation toward more favorable cartilage repair outcomes, underscoring
cartilage and bone in osteochondral defects . PRP has the significance of employing supplementary seed cells in
[48]
also been incorporated into the GelMA hydrogel. Jiang hydrogel-based cartilage therapy.
et al. developed PRP-GelMA hydrogels with superior The UV-mediated photocrosslinking properties,
[49]
cartilage and subchondral bone repair abilities. These adhesive affinity for cells, and biodegradable nature render
hydrogels not only promoted the migration, osteogenesis, GelMA the most suitable ink for 3D printing. Moreover,
and chondrogenesis of BMSCs but also contributed to the layer-by-layer assembly through 3D printing allows for
regulation of immune response and M1-to-M2 transition the even distribution of cells within the scaffolds, a crucial
of macrophages. Irmak et al. constructed a GelMA/ aspect for tissue regeneration since endogenous cells are
[50]

Volume 9 Issue 6 (2023) 250 https://doi.org/10.36922/ijb.0116