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Osidak, et al.
II (COL-II) and COL-X expression indicated that began to increase. Gross encapsulation of the
zonal cartilage regeneration was reached. implanted scaffold, which additionally indicates
An alternative approach was proposed by an inflammatory reaction, was also noted.The
Yang et al . [34] . In this work, to prepare the bioink, concentration of CD3 biomarker (that is an
collagen (15 mg/ml) was mixed with alginate indication of an inflammatory process) was reduced
(sodium alginate SA/COL). Then, primary compared with the first stage. However, the gross
chondrocytes isolated from articular cartilage encapsulation of the implanted scaffold shows that
of new-born rats were added to the mixture. As the inflammation process is still presented.
a comparison, two types of other bioinks were At the stabilizing stage (8 – 12 weeks), peak
used: Bioink made from agarose (AG) and bioink values of elastin, vimentin, and alpha-SMA
made from a mixture of alginate and AG (SA/ production were noted. This indicates the active
AG). When comparing SA/COL with SA/AG and deposition of collagen by infiltrated cells and the
SA, the proliferation and survival of chondrocytes strengthening of the extracellular matrix in the
were significantly promoted in the case of SA/COL bioprinted scaffold. However, compared with the
bioinks. The expression of specific gene markers previous stage, there was no significant increase in
of cartilage, including Sox9, Acan, and Col2a1, the mechanical properties of the implanted material.
was also significantly higher in SA/COL group. This work of Maxson et al. is of particular
interest due to the demonstrated recellularization
3.3 Cardiovascular tissues potential of a bioprinted aortic heart valve scaffold
from a highly concentrated type I collagen
In general, the research work on bioprinting for hydrogel. Furthermore, an increased level of the
cardiovascular tissue regeneration is focused on CD3 marker expression in experimental animals
myocardium, heart valves, and vasculature . may be associated with the presence of residual
[35]
Maxson et al. have demonstrated the potential gelatin from FRESH slurry and allogeneic rat cells
[14]
of the use of the highly concentrated type I collagen in the construct.
hydrogel for the heart valve bioprinting. In addition Despite concerns of inducing a systemic
to collagen, the bioink contained rat MSCs. With immune response, it is worth noting that the
this bioink, Maxson et al. managed to print collagen indisputable advantage of FRESH technology is
disks of 1 mm in thickness and 28 mm in diameter the ability to 3D print the human heart components
onto a FRESH slurry. After slurry removal, the at various scales from capillaries to the full organ
printed structures were subcutaneously implanted with a high degree of accuracy. For example,
into rats. The implanted samples were extracted Lee et al. have printed a simplified model of a
[15]
at 2, 4, 8, and 12 months with the subsequent small coronary artery–scale linear tube from COL
study on their mechanical properties, evaluation for perfusion with a custom-designed pulsatile
of cell infiltration, and determination of levels of perfusion system. The linear tube had an inner
specific inflation markers expression. The profile diameter of 1.4 mm and a wall thickness of ~300
of stress-strain curves of the bioprinted aortic μm. C2C12 cells within a collagen gel were cast
heart valve scaffolds indicated that scaffolds have around the printed collagen tube. Only in case of
transitioned through phases of resorption, synthesis, active perfusion through the collagen structure,
stabilization, ultimately, and remodeling. cells remained alive in their entirety. Next, they
At the resorption stage (2 – 4 weeks), the printed the left ventricle of the heart using human
mechanical properties of implanted scaffolds were stem cell-derived cardiomyocytes. The ventricle
reduced. Moreover, the increased expression of was designed as an ellipsoidal shell with inner
CD3 biomarker from acute inflammation was also and outer walls of collagen and a central core
noted during this period. region which contained cells. Cardiac ventricles
At the synthesis stage (4 – 8 weeks), the printed with human cardiomyocytes showed
mechanical properties of implanted scaffolds synchronized contractions, directional action

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