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International Journal of Bioprinting 3D-Printed GelMA biomaterials in cartilage repair
tissues directly, but it may improve tissue integration physical properties of GelMA hydrogels, specifically the
by promoting the synthesis and deposition of ECM stiffness, play an important role in maintaining chondrocyte
components, such as glycosaminoglycans and collagen. phenotypes. Additionally, the microporous structure of
Zhan fabricated the PEGDA into GelMA hydrogels and gelatin hydrogels was found to have varying effects on
[24]
obtained hydrogels with different ligand adhesion densities chondrocytes, with non-microporous gelatin hydrogels
and stiffness properties. PEGDA is a hydrophilic polymer being beneficial for maintaining the cartilage phenotype
that attracts water molecules and forms a hydrated layer of chondrocytes and microporous GelMA hydrogels being
on its surface. This hydrated layer can help to promote more suitable for chondrocyte proliferation . Hyaluronic
[29]
cell adhesion by mimicking the ECM of living tissues. acid methacrylate (HAMA) is also an excellent material
Brown et al. incorporated thiolated heparin (HepSH) for cartilage regeneration and is added to GelMA for
[25]
into GelMA hydrogel containing chondrocytes. HepSH is biomimetic approach. Costantini et al. prepared GelMA,
[30]
able to bind to various biomolecules and surfaces, allowing GelMA+CS-AEMA (chondroitin sulfate amino ethyl
it for easy conjugation to other biomaterials, creating methacrylate), and GelMA+CS-AEMA+HAMA, three
a stable and biologically active material. Introducing kinds of bioinks containing BMSCs. The incorporation of
HepSH promoted cell differentiation and cartilage matrix chondroitin sulfate (CS) and HAMA enhanced cell viability
deposition in vitro. Wang et al. introduced GelMA with and chondrogenesis of BMSCs, showing the potential for
[26]
ε-polylysine (EPL) and phenylboronic acid (PBA) to create advanced engineering of cartilage tissue. Shopperly et al.
[31]
a modified Gel-EPL/PBA hydrogel. EPL can interact with chose HAMA and GelMA as bioinks to mimic the zonal
negatively charged cell surfaces and ECM components, structure of articular cartilage. They discovered that cell-
making it a potential material for tissue engineering and laden constructs supported the growth and secretion of
drug delivery systems. These GelMA hydrogels modified proteoglycans and type II collagen of chondrocytes.
by EPL and PBA enhanced the growth of chondrocytes In summary, GelMA with modifications shows
and the chondrogenesis of stem cells, as well as promoted promising results for cartilage repair, and thus, they are
the cartilage defects repair. PBA has the ability to bind extensively applied in cartilage tissue engineering.
to sugars and other molecules that contain diols, such as
glucose. Overall, the use of these approaches that improve The incorporation of different materials to GelMA
the adhesive properties of GelMA hydrogels significantly hydrogels showed potential in developing “smart” scaffolds
enhances cell differentiation and cartilage matrix that regulate cell behavior and controlled drug release.
deposition, and promotes tissue integration, broadening Further modifications and improvements to GelMA-based
the application of GelMA hydrogels in cartilage tissue inks are needed to enable the fabrication of 3D constructs
engineering. with multiple components and organized structures that
can better mimic the complex properties of articular
The RGD peptide family is a unique recognition site
for integrin receptors, which play a vital role in cell–cell cartilage.
and cell–extracellular communication. To promote tissue
regeneration, researchers have explored using RGD 5. Application of GelMA-based materials in
peptides-PFS (peptide sequence PFSSTKT) to create the 3D printing cartilage tissue engineering
functional GelMA/ECM-PFS hydrogels that enhance the
mechanical properties of GelMA, recruit BMSCs, and The good biocompatibility and flexible characteristics
improve hyaline cartilage repair in rabbits . of GelMA hydrogels make them suitable as scaffolds to
[27]
explore cell–matrix and cell–cell interactions and serve
In summary, improving the integration between as 3D supports for soft tissue regeneration. Moreover, the
GelMA and in situ cartilage tissues can substantially unique properties make the GelMA hydrogels widely used
bolster the regeneration of neocartilage. Nonetheless, there biological inks for 3D printing, allowing for the creation of
are no methods identified thus far that could be deemed customized patterns, components, and architectures that
flawless. This underscores the necessity for the exploration can be tailored to specific tissue engineering applications .
[13]
of innovative strategies in future.
Articular cartilage defects often involve the regeneration
4.3. Cell behavior regulation of multiple tissues, including hydroline cartilage, calcified
In addition, the physical properties of GelMA hydrogels cartilage, and subchondral bone, and this highly organized
have varying effects in maintaining chondrocyte tissue is specialized for its function. With advancements
phenotypes, which play a crucial role in cartilage repair. Li in 3D printing technology, it is now possible to fabricate
et al. conducted studies to investigate the effects of GelMA tissue constructs that closely resemble target tissues in
[28]
hydrogels on chondrocyte phenotypes. They found that the both structure and composition, which is a significant
Volume 9 Issue 6 (2023) 245 https://doi.org/10.36922/ijb.0116

