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Hydrogel based 3D-printing Bioinks for Cartilage Repair
mild crosslinked hydrogel with low cytotoxicity . Since GelMA. The scaffold was then embedded with porcine
[73]
GelMA was introduced by Van Den Bulcke et al. in 2000, chondrocytes of different concentrations to investigate
several studies have shown that the physical properties its biocompatibility and repair efficacy . Significant
[81]
and cell response parameters of GelMA could be tuned by chondrogenic differentiation and enhanced cartilage ECM
manipulating its synthesis and processing. For example, formation was observed after 14 days of in vitro culture.
a study in 2012 demonstrated that the compressive The shapes and distribution of cells were also maintained
modulus of GelMA was directly correlated with the throughout the 2 weeks. In addition, GelMA scaffold with
degree of methacryloyl substitution . Cryogenic high chondrocyte density promoted cartilage-specific
[74]
treatments, including freeze-drying, can also help control COL type II formation compared to the MeHA-based
the pore sizes of the GelMA hydrogel . In addition, the constructs . In 2020, Luo et al. developed a BMSCs-
[75]
[81]
stiffness of this material can be modified by the degree of containing bioink with 5% of GelMA . This cell-laden
[82]
crosslinking . As for its biocompatibility, the arginine- GelMA hydrogel was capable for the construction of
[76]
glycine-aspartic acid sequence contained in GelMA is scaffolds with accurate and complex shapes. In addition,
significant for promoting cell attachment , indicating BMSC differentiation and generation of cartilage fiber
[77]
a potential capability for promoting chondrogenesis. tissue were observed after 4 weeks since the GelMA
High cell viability is also observed in cell-laden GelMA scaffold was implanted intramuscularly in nude mice.
hydrogel . As for its disadvantages, studies have In a more recent study by Irmak and Gümüsderelioglu,
[73]
revealed that GelMA-pure hydrogel is poor in mechanical a photocrosslinkable hydrogel consisting of GelMA and
strength compared to the initial cartilage tissue. It also PRP, which contains various growth factors, was 3D
exhibits a high swelling rate, which increases wound printed into tissue-specific structures . The GelMA/PRP
[83]
pressure and results in the lack of stability required for scaffold could significantly promote the proliferation and
the maintenance of space for cartilage regeneration . differentiation of ATDC5 cells as suggested by in vitro
[78]
The application of GelMA in 3D printing is advancing
in recent years. In 2019, Chen et al. built a 3D-printed cell culture study. However, the authors did not provide
information about the efficacy of cartilage repair in vivo
cartilage ECM/GelMA/exosome scaffold to deliver
mesenchymal stem cell exosomes, which is significant for by this novel material.
the disorder of intercellular mitochondria communication 2.6. PEG
in OA . The construct was printed successfully by a
[79]
stereolithography-based 3D printer with a resolution of PEG hydrogel is composed of synthetic liquid-swollen
0.05 mm and suitable pore size (100 – 500 μm). By using polymer networks (Figure 4D) that have been approved
the rabbit model, the authors also showed that the ECM/ by the Food and Drug Administration for medical
GelMA/exosome scaffold was able to restore the functions applications in human and have become one of the
of chondrocyte mitochondrial to enhance chondrocyte most popular resources to design hydrogels for cartilage
migration and cartilage regeneration . In the same repair . It can be synthesized by photopolymerizing
[80]
[84]
year, Lam et al. also developed a bioink consisting of PEG precursors with the addition of photoinitiators .
[85]
Table 3. Conclusion of the gelation methods, biocompatibility, advantages and disadvantages of hydrogels mentioned in this article. The
score goes from “+” to “+++”, suggesting relatively low, medium and high biocompatibility.
Materials Gelation methods Biocompatibility Highlight Reference
HA 1. Chemical agents ++ Bioactive properties but poor of mechanical [32,66,97]
2. Photocrosslinking strength, which can be improved by crosslinking
3. Electropolymerization with materials such as PEG.
Alginate Cation adding +++ Suitable flexibility and shear-thinning capability, [44,45,66,97]
but poor of biomechanical properties and
stability.
Collagen 1. Chemical agents +++ Good biocompatibility with inferior viscosity [11,59,66,73]
2. Physical methods and mechanical properties; crosslinking via
(heating, drying, chemicals may involve toxic agents.
irradiation e.g.)
Silk 1. Chemical agents ++ Low adverse immune reaction, tunable [66,69]
Fibroin 2. Cryogelation degradation rate and elasticity; crosslinking via
chemicals may involve toxic agents
GelMA Photocrosslinking +++ Fast gelation and tunable properties; low [73,76,77]
cytotoxicity but lacks mechanical strength.

22 International Journal of Bioprinting (2022)–Volume 8, Issue 3