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International Journal of Bioprinting 3D bioprinting for vascular system
3.1. Bio-inks with good biomechanical properties into a printable biomaterial . Tissue-engineered vascular
[32]
Research in 3D bioprinting focuses on developing bio- grafts use cell-laden (containing 3 × 10 cells per mL)
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inks suitable for printing small-diameter blood vessels. bio-ink composed of 7.5% (w/v) gelatin and 10 mg/mL
By mixing different kinds of natural and artificial fibrinogen .
[32]
compounds, adjusting the formula concentration can
effectively improve the biomechanical properties of 3.2. Sophisticated printing strategy
biological ink. Designing a sophisticated printing strategy can effectively
improve the printing precision of small-diameter blood
Zhou et al. introduced alginate lyase into natural ink vessels. Zhou et al. developed an interfacial diffusion
to improve the biological activity of biological ink and printing (IDP) technique to control the thickness and
gradually degrade alginate, which played a supporting diameter of the tube wall structure by controlling the time
role in the substrate . The wall structure printed by the of gel crosslinking inside and outside the tube . Jin et al.
[27]
[33]
ink mixed with lyase contains a more porous structure. developed a method for making hollow blood vessels
Endothelial cells and smooth muscle cells in the vascular without relying on sacrificial materials and used a two-step
wall have higher nutrient exchange efficiency and larger crosslinking method . The semi-solid wall with a quarter of
[34]
adherent proliferation space. The growth rate of smooth lumen size was prepared by crosslinking in the first step, and
muscle cells in the lysozyme group was significantly faster then the concave structure with a 3/4 lumen size was made
than in the non-lysozyme group. The density of smooth by covering the GelMA not crosslinked in the second step.
muscle cells and endothelial cells encapsulated in the bio- Two separate parts constructed a complete tubular structure
inks is 1 million per mL . After adding an acellular ECM with a two-step crosslinking. Using no sacrificial material
[27]
from the great saphenous vein to bio-ink, Kamaraj et al. avoids damage to existing vascular structural accuracy and
found that dECM induced the differentiation of human cell activity during removal. This method provides a new way
umbilical cord mesenchymal stem cells (UMSCs) into to improve the printing precision of tubular structures .
[34]
vascular smooth muscle cells and enhanced alpha-smooth Instead of printing layer by layer, Zhang et al. used a robotic
[28]
muscle actin (α-SMA) expression . They constructed arm with six degrees of freedom (6-DOF) to build a new
the vascular structure with a high cell integration rate 3D bioprinting system . Composed of six 360° rotating
[35]
successfully, and the density of UMSCs encapsulated in the joints, the manipulator can print routes from all directions
[28]
bio-inks is 10 million per mL . in 3D space, significantly improving the ability to bioprint
To enhance the mechanical properties of bio-inks, Gold complex anatomical structures. They also successfully used
et al. blended gelatin methacrylate (GelMA), polyethylene the dual-robot platform to print a stent similar to the heart
[35]
glycol diacrylate (PEGDA), and two-dimensional nano- coronary artery network complex shape (Figure 2) .
silicate to develop a new high-viscosity bio-ink . Nano-
[29]
silicates enhanced the compression elasticity of blood vessel 3.3. Combined multiple manufacturing technologies
walls, showed high printability regardless of cell density, In the past, single processing methods were used to
and protected encapsulated cells from high shear forces manufacture small-caliber blood vessels, but the blood
during bioprinting. The authors selected a cell density vessels fabricated by these processes, when used alone,
of 2.5 million cells per mL for developing this vascular were unable to mimic the complex structure and function
model . Li et al. also found that doping the bio-ink with of the natural small-caliber blood vessels. Integrating
[29]
carbon nanotubes could improve the mechanical strength multiple manufacturing technologies into a single
of the stent . The authors successfully made engineered biofabrication platform can effectively compensate for the
[30]
blood vessels with an inner diameter of 3 mm from bio-ink limitations of a single processing method. The current 3D
containing carbon nanotubes with a cell concentration of bioprinting technology is limited to a resolution of close to
[30]
4 × 10 cells per mL . Liu et al. designed a double-network tens of microns. It cannot effectively print the nanoscale
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hydrogel by chemically crosslinking bio-inks, using ECM structure, thereby hindering the reproduction of the
calcium ion-crosslinked alginate to form the first network microenvironment for blood vessel cells. Electrospinning
of a two-network hydrogel . They used polyacrylate and uses high pressure to produce nanoscale diameter fibers
[31]
PEGDA as polymer crosslinkers to prepare the secondary with a large specific surface area that can mimic the
network structure of double-network hydrogels. The physical function of the natural ECM, providing many
vascular structure printed by the double-network hydrogel attachment points for cell adhesion and growth. Fazal et al.
has high toughness and elastic properties . Freeman et al. developed a hybrid device that combines bioprinting and
[31]
[36]
combined fibrinogen and gelatin, using gelatin’s excellent electrospinning . The device, which has a bioprinting
rheological properties to convert non-printable fibrinogen head and two electrospinning heads, is capable of
Volume 9 Issue 6 (2023) 261 https://doi.org/10.36922/ijb.0012

