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Hydrogel based 3D-printing Bioinks for Cartilage Repair
and subchondral bone in rabbits with osteochondral with PCL/alginate/chondrocyte/TGF-β scaffold showed
defects. In addition, instead of using UV light, the GelMA- significantly more COL fiber and better cartilaginous
MeHA scaffold could gelate via the illumination of visible tissue formation. However, the long degradation period of
light. On the other hand, acellular HA scaffold has been PCL could prevent tissue ingrowth . Later, Kosik-Kozioł
[53]
used to deliver growth factors, including human leukocyte- et al. formulated an alginate/short submicron polylactide
platelet-rich plasma (PRP) and leukocyte-platelet-rich ink in 2017 . This material was able to increase Young’s
[54]
fibrin, to cartilage defects. The following in vivo results modulus of printouts threefold compared with that of
confirmed that the newly generated cartilage tissue had pure alginate scaffold. Neocartilage ECM deposition was
improved biomechanical strength by these growth factor- also observed during in vitro experiments. More recently,
loaded HA scaffold . Olate-Moya et al. designed a new ink by conjugating
[42]
photocrosslinkable alginate with gelatin, chondroitin
2.2. Alginate sulfate, and graphene oxide, which further enhanced the
[55]
Alginate is a biocompatible, biodegradable gelling printability of this material . The 3D printed scaffold via
agent that can be obtained from the cell wall of brown the microextrusion process exhibited optimized resolution
seaweed . It is composed of 1,4-β-D-mannuronic acid and increased cell proliferation when carrying human
[43]
(M) and 1,4-α-L-guluronic acid (G). Longer M or G adipose tissue-derived mesenchymal stem cells. In the
blocks divided by MG alternating regions organized into same year, Schwarz et al. used an oxidized alginate-gelatin
this long anionic linear copolymer, which has suitable hydrogel together with human nasoseptal chondrocytes to
flexibility and shear-thinning capability required by 3D create 3D printed grid-like scaffolds, which showed high
[56]
printing (Figure 4E) . Alginate hydrogels are usually shape fidelity and improved resolution .
[44]
crosslinked rapidly by dropping an alginate solution into 2.3. COL
a calcium ion liquor, such as calcium chloride (CaCl )
2
solution . The compressive modulus of alginate inks is COL is the most common protein in human and is a
[45]
about 30 kPa, which is higher than that of native human major component in ECM. It supports the regeneration
articular cartilage, which is about 10.60 ± 3.62 MPa [46,47] . of several connective tissue, including bone, cartilage,
Owing to fast degradation rates, they are also considered and skin . In general, polypeptide chains constituting
[57]
to be lacking biological stability, which is important for COLs are composed of a sequence of different peptides
cell viability . Currently, scientists have found that (glycine-X-Y) , in which X and Y are usually proline and
[48]
3
oxidation of alginate was able to improve the in vivo hydroxyproline (HYP) (Table 4) (Figure 4B) . For many
[11]
biodegradability of alginate-based inks by creating more years, COL-bioink has been regarded as a biocompatible
reactive sites . Yang et al. also demonstrated that alginate material, as it can provide anchor sites for cell adhesion .
[58]
[49]
bioink combined with COL I or agarose showed improved However, the traditional procedure for the cross-linking
mechanical strength, with the compressive modulus of COL hydrogel usually includes the addition of toxic
increased by over 1.87- and 2.38-fold, respectively . chemical agents, such as glutaraldehyde and 1-ethyl-3-(3-
[47]
Coating 3D-printed alginate scaffold with homogeneous (dimethylamino)propyl) carbodiimide . In addition, the
[59]
nano apatite has also been shown to significantly improve degradation rate of the 3D-printed COL scaffold is impacted
Young’s modulus of the construct and the differentiation by various factors, including the penetration of cells and
rate of encapsulated rat bone marrow cells . the presence of non-specific proteinases. It means that the
[50]
Alginate-based bioinks have been applied widely in extent and rate of degradability of COL-based scaffolds is
cartilage tissue engineering during the recent decade. Back difficult to control . For its printability, it is difficult for
[11]
in 2012, scientists used alginate hydrogel to demonstrate printouts by COL-bioink to maintain porous structure due
that the 3D printing techniques could be applied in to its inferior viscosity and weak mechanical strength .
[60]
osteochondral tissue engineering for the 1 time . In Thus, applying COL directly as a source for bioink is tough.
[51]
st
2014, researchers developed a novel ink using alginate/ The properties of COL can be tuned by blending with
acrylamide solution with an epoxy-based UV-curable other materials or tailoring its fibrillogenesis, including the
adhesive. It was shown to improve the mechanical strength enzymatic process. In 2016, Shim et al. built a 3D-printed
of the printed scaffold compared with that composed of scaffold with hMSCs and hydrogel composed of HA and
pure alginate . In 2015, Kundu et al. built a 3D scaffold pepsin-treated COL (atelocollagen) [61] . The crosslinking
[52]
consisting of alginate hydrogel with chondrocytes and process of this bioink did not involve any cytotoxic
layer-by-layer deposition of polycaprolactone (PCL) reagent. Results showed that the knee joint defect of
(Table 4) . Cells encapsulated showed up to 85% viability rabbits with this construct implanted was covered by
[53]
immediately after printing, but the long-term effects thick neocartilage tissue at the center space at week 8.
were not examined. In addition, by using nude mouse But the expression of COL X, which is usually restricted
model, the authors demonstrated that mice implanted to the lower part of articular cartilage, was observed in
20 International Journal of Bioprinting (2022)–Volume 8, Issue 3