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

unable to migrate into the scaffold immediately, contingent excellent printability and a high cell survival rate. In
on the scaffold’s composition and structure. Herein, we addition, 5% (w/w) GelMA loaded with BMSCs promotes
summarize different types of cells loaded in the GelMA cartilage-specific ECM deposition and cartilage formation.
hydrogels for 3D printing in cartilage tissue engineering.
These studies focused on evaluating the role of GelMA
Stem cells and chondrocytes have been extensively in the chondrogenic and/or osteogenic differentiation of
encapsulated in GelMA for cartilage tissue engineering. stem cells in vitro, but a few studies have explored the use
of GelMA carrying stem cells in cartilage repair in vivo. Liu
[55]
5.2.1. Stem cells et al. found that dendrimer-modified GelMA hydrogels
Stem cells are recognized as excellent seed cells for cartilage carrying ADSCs promoted cartilage regeneration in vitro
repair since stem cells come from a wide range of sources , in 3D culture of rat ADSCs and articular cartilage defect
[53]
such as embryonic stem cells, mesenchymal stem cells, repair in vivo. The scarcity of studies may be attributed to
induced pluripotent stem cells, and cartilage progenitor the prevalent focus on GelMA hydrogels fabricated using
cells. They are easy to obtain and have multi-differentiation traditional scaffold fabrication techniques.
potentials, including chondrogenesis. GelMA-based 5.2.2. Chondrocytes
hydrogels that can help the osteochondral differentiation Chondrocytes are the primary cell type in cartilage tissue
of stem cells to achieve cartilage regeneration have been and they play an essential role in forming new cartilage
extensively studied with the traditional scaffold fabrication matrix . Maintaining the phenotype of chondrocytes
[62]
techniques . For instance, Huang et al. constructed a is a major challenge in cartilage tissue therapies. In
[54]
[27]
GelMA hydrogel combined with BMSCs affinity peptide recent studies, different GelMA-based hydrogels have
sequence PFSSTKT (PFS)-modified chondrocyte ECM been used, owing to their potential in promoting
particles (GelMA/ECM-PFS), which could regulate the the proliferation, migration, and differentiation of
migration of rabbit BMSCs in vitro and recruit endogenous chondrocytes for cartilage tissue engineering. Levett
BMSCs to migrate to the defect sites, resulting in a hyaline et al. found that GelMA was the best hydrogel in
[63]
[55]
cartilage repair. Liu et al. found that dendrimer-modified promoting the proliferation of chondrocytes, as well as
GelMA hydrogels carrying ADSCs promoted cartilage the secretion of ECM abundant in glycosaminoglycan
regeneration in vitro in 3D culture of ADSCs and articular and collagen, compared to other commonly used
cartilage defect repair in vivo. hydrogels, such as hyaluronic acid, polyethylene glycol,
In addition, articular chondrogenic progenitor cells and alginate hydrogels. Hölzl et al. also demonstrated
[64]
(ACPCs) are present mainly on the surface of articular that GelMA has good integration with surrounding
cartilage and play an essential role in chondrogenesis and cartilage, enabling the sealing and smoothening of local
injury repair [56,57] . In promoting cartilage regeneration, gaps while facilitating the migration and growth of
Levato et al. compared the differences between cells for new tissue formation. Wang et al. loaded the
[58]
[65]
ACPCs, chondrocytes, and MSCs, and found that ACPCs chondrocyte spheroids into a hydrogel mixture of GelMA
outperformed chondrocytes in forming neocartilage. and HAMA which maintained chondrocytes phenotypes
Furthermore, Mouser et al. also discovered differences and enhanced proliferation, demonstrating its potential
[59]
in chondrogenesis among these three types of cells. To as a micro-unit for cartilage tissue engineering. Levett
exploit these differences, they combined ACPC- and MSC- et al. found that introducing HAMA and CSMA
[66]
laden bioinks to print a more biomimetic scaffold, hoping could enhance chondrogenesis and promote secretion of
that the two cell types could differentiate toward different proteoglycan and collagens, making CSMA a promising
lineages [58,59] . option for cartilage tissue engineering. Agten et al.
[67]
found that GelMA loaded with chondrocytes derived
Despite the fact that 3D printing showed better
potential than traditional scaffold fabrication techniques, from human induced pluripotent stem cells formed
the studies on GelMA as a carrier of stem cells for articular hyaluronic cartilaginous tissue in vivo. Overall, GelMA
has shown promising results in promoting chondrocyte
cartilage regeneration in the context of 3D printing remain proliferation and ECM secretion, and integration
scarce. Gao et al. used polyethylene (ethylene glycol) with surrounding cartilage, making them promising
[60]
dimethacrylate (PEG), GelMA, and human MSCs to create candidates for cartilage tissue engineering.
osteocartilage tissue constructs. They discovered that
human MSCs were evenly distributed and had excellent However, it is surprising that there are few reports on
osteogenesis and chondrogenesis capacity. Similarly, Luo chondrocyte-laden GelMA hydrogels printed for articular
et al. constructed GelMA laden with BMSCs using low- cartilage tissue engineering. The reason may be because
[61]
temperature 3D printing and found that GelMA displayed numerous reports on chondrocyte-laden GelMA hydrogels

Volume 9 Issue 6 (2023) 251 https://doi.org/10.36922/ijb.0116