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Mei, et al.
increase in moduli, biochemical expression, and cartilage excellently with the native tissue and promote
regeneration (Figure 3Bii). osteochondral repair. In another study by the same group,
In a 3D bioprinting process, the interaction between Cui et al. further printed mechanically strong and tissue
cell patterning and hydrogel matrix has a great effect on differentiated bone and cartilage constructs using photo-
the performance of printed cells. For instance, Lutz Klok crosslinkable PEG-GelMA hydrogel with hMSCs . The
[55]
et al. fabricated different 3D cartilage tissue constructs printed constructs provided strong mechanical support
with different cell concentrations (Figure 3C) . The and showed an excellent osteogenic and chondrogenic
[75]
bio-inks were prepared by homogeneously mixing cell regeneration capacity, suggesting their desirable potential
suspensions with GelMA or HAMA hydrogel separately in osteochondral repair. Recently, Gao et al. developed
and then printed in a layer by layer process through a biohybrid gradient construct for osteochondral
SLA-based bioprinting. Histological staining indicated regeneration by 3D bioprinting (Figure 4A) . By
[79]
that cells distributed homogeneously in both GelMA incorporating cleavable poly (nacryloyl 2-glycine)
(Figure 3Ci-iii) and HAMA constructs (Figure 3Civ-vi). (PACG) into GelMA, the mechanical properties of
A noticeable difference in cell number can be observed hydrogels had been significantly improved with a tensile
between low and high cell density constructs. Results strength of up to 1.1 MPa and a compressive strength up
indicated that both GelMA scaffolds and HAMA to 12.4 MPa (Figure 4B). Results demonstrated that the
scaffolds supported the recovery of chondrocyte photo-crosslinkable gradient hydrogel scaffold could not
phenotype and formation of cartilage ECM with only facilitate the regeneration of cartilage (Figure 3Ci-ii)
uniform cellular distribution. Meanwhile, the increase but also promote the regeneration of subchondral bone
in cartilage-specific genes expression, type II collagen, (Figure 4Ciii-iv).
and aggrecan, in cell loaded hydrogels proved successful
cartilage formation. Compared with HAMA, GelMA 4.4. Bioprinted hydrogels in bone disease model
showed more chondrocyte phenotypes as confirmed by Apart from the above discussed applications, 3D
the higher expression of cartilage genes. Another element bioprinted hydrogels can also be used to create bone
that affects cartilage formation is the cell density; a high disease models and drug screening research. At present,
cell density (2.5×10 cells/mL) showed better cartilage most bone disease models are still 2D, which fails to
7
regeneration ability compared with a low cell density reconstruct the complex of the in vivo environment .
[80]
(5×10 cells/mL). Conversely, 3D bioprinting has the promising potential to
6
4.3. Bioprinted hydrogels in osteochondral tissue create 3D mimic bone models as discussed in the previous
engineering sections, allowing for cell-cell or cell-matrix interactions
and integration of a vascular system . Hence, these
[81]
Osteochondral defect involving both the cartilage bioprinted models could be better used for bone disease
and subchondral layer is difficult to repair due to their study and drug screening purposes .
[82]
difference in physiological structures and bioactive For example, 3D-printed tissue models mimicking
properties. The cartilage tissues do not have vasculature the native bone tissues can be applied in drug screening
and nervous systems but the subchondral bone tissues to test the efficacy and toxicity of new drugs, and
are rich in blood and nerves. In addition, the structure promoting the translation of new therapeutic molecules in
and function of cartilage and subchondral bone are clinic . Recently, Amir K et al. designed and bioprinted
[83]
also different . Thus, how to promote cartilage and a musculoskeletal junction model mimicking the
[76]
subchondral bone regeneration simultaneously has musculoskeletal interface by an SLA-based bioprinting
become quite the challenge for osteochondral repair. The platform (Figure 5Ai) . Photo-crosslinkable GelMA
[84]
rise of 3D bioprinting, allowing for the fabrication of was selected as a bio-ink due to its high biocompatibility
complicated 3D scaffolds with precise control of intricate for cell spreading and functionality. The musculoskeletal
geometry composition and functions, is a promising interface is loaded with three different cell types, MSCs,
treatment for osteochondral repair. Meanwhile, photo- fibroblasts, and osteoblasts (Figure 5Aii). As shown in
crosslinking hydrogels are promising bio-inks for Figure 5Aiii-iv, the printed 3D pattern has a well-defined
osteochondral regeneration as we discussed in the construct showing a close similarity with the designed one
previous chapters . (Figure 5Aii). The proposed musculoskeletal junctions
[77]
In an earlier study, Cui et al. bioprinted a photo- provide a multi-material microstructure on demand for
crosslinkable 3D osteochondral tissue using PEGDMA multi-applications in skeletal related tissue engineering
and human chondrocytes. Simultaneous photo- and regenerative medicine, thus facilitating new drug
polymerization maintained the precise positions of discovery and clinical use.
deposited cells and reduced photo toxicity . This In addition, 3D-printed tissue models could also be
[78]
bioprinted cell-laden hydrogel constructs integrated applied in creating cancer models for cancer metastasis
International Journal of Bioprinting (2021)–Volume 7, Issue 3 45