Page 420 - IJB-9-4

International Journal of Bioprinting 3D bioprinting of artificial blood vessel

cells influences the physical properties and forming ability cells, respectively [51-53] . The proliferation rate of EC varies
of hydrogels . Before printing, the hydrogels need to keep with the hardness of their growth surface, and all the
[39]
the cell in suspended state; during extrusion printing, the experimental results pointed to the importance of stiffness
cell activity will be influenced significantly by the stress. as a determinant of cellular behavior .
[53]
After the forming process, the solid printed structure needs At present, the mechanism of the printing process with
to ensure the smooth transportofnutrients . The inserted hydrogels or bioinks loaded with cells for a long term is
[40]

cells will occupy specific positions in the bioink, which may not very clear . The shear forces always contribute to the
[54]
affect the cross-linking efficiency and viscoelasticity of the deformation of cells, leading to the rearrangement of the
bioink . In the HA hydrogel, the gelation time remains cytoskeleton after a few rounds of printing process . The
[41]
[55]
7
the same with a cell density of 2.5 × 10 cell/mL; however, change of cellular morphology has been found to regulate
the gelation time increases from 20 to almost 60 min the cell behavior and differentiation . For example,
[56]
when the cell density rises to 1 × 10 cell/mL. After the cell the MSCs differentiate into osteogenic lineages on the
8
density achieving 2.50 – 5.0 × 10 cell/mL, the HA cannot stimulation of stretch , and the stretching state induces
8
[57]
cross-link as usual, resulting in a significant decrease in the EC to release more nitric oxide . Thus, the external
[58]
viscosity . Billiet et al. found that the blending of cells and internal factors that influence the cell behavior are
[42]
impacts solution viscosity. Above the gelation temperature, complex and related to many physical factors, as shown
the viscosity decreased by 2-fold until the cell density in Figure 2. Therefore, a deep understanding of the factors
reached 1.5× 10 cell/mL. Increasing the cell density
6
further to 2.5 × 10 cell/mL increased this factor to 4 . underlying cell stress would help lay a foundation in the
[43]
6
[59-61]
Cell metabolism also affects the chemical process of cross- relevant bioprinting protocol in the future .
linking; for instance, the reactive oxygen species produced 3. Bioinks for 3D bioprinting
by photoinitiators can be absorbed by cells, decreasing the
[44]
efficiency of cross-linking . With the rapid development of material printing, many
companies have developed bioinks for specific tissue
2.3. Forming requirements engineering applications; for example, Organovo’s Novo-
[62]
The blood vessel is a structure that delivers blood under Gel has been used for bioprinting aortic vascular grafts .
hemodynamic pressure; thus, the artificial blood vessels It is difficult for the existing hydrogel system to fulfill
must be strong enough to withstand the pressures . Burst the requirements, such as attaining the same mechanical
[45]
[63]
pressure compliance, anti-fatigue perfusion, in vivo graft property of some organs and the optimal biocompatibility .
effectiveness, and suture retention are the most important The novel bioink should always be strategically designed
criteria for vascular graft selection . Bursting pressure is based on the requirements of the arterial blood vessel and
[46]
the maximum pressure; the graft can withstand before the prepared using suitable cross-linking methods and composite
occurrence of acute leakage. This pertains to the relation recipe. According to the function of hydrogel in the printing
between the maximum circular force (σ) and burst pressure process, the hydrogels are classified into support materials
(P) per unit area. From the formula σ=Pd/2t, the bursting and scarified materials, and the support materials are further
[64]
pressure increases as the diameter decreases, which means categorized into natural and synthetic polymers . The
that the burst pressure of the small-caliber blood vessel will major reason that the bioprinting of arterial blood vessel
be higher than that of the normal caliber blood vessel . would fail is the lack of intact inner intima, which leads to
[47]
Therefore, the microvessel structure prepared using platelet adhesion and aggregation as well as thrombosis [65,66] .
hydrogel has higher requirement on strength . It is better to use the EC as the bioprinting materials to
[48]
rebuild the inner intima as soon as possible. The shear force
Besides, the stiffness (elasticity) of vascular structure is from the nozzle could influence the micromorphology and
an important attribute that determines cell activity. Several function of the bioprinted cells, decreasing the adhesion,
studies found that the cell migration decreased with an proliferation, and viability of cells . Thus, the other purpose
[67]
increase of stiffness, and the differentiation of marrow of the hydrogels is to protect the cells during the printing
mesenchymal stem cells (MSCs) is also dependent on process . In this section, the advantages of each hydrogel in
[68]
hydrogel stiffness [49,50] . Compared with MSCs cultured on the preparation of arterial blood vessel are discussed.
100 kPa hydrogels, the MSCs cultured on 30 kPa hydrogels
secrete more immunomodulatory and regenerative factors, 3.1. Support hydrogel
indicating that the MSC differentiation may be determined 3.1.1. Synthesis hydrogel
by the stiffness of basement: The soft, medium hardness,
and hard basements could facilitate the differentiation As proven by the U.S. Food and Drug Administration
of the MSCs into nerve cells, muscle cells, and bone-like (FDA), PEG is a biocompatible material, whose main chain
Volume 9 Issue 4 (2023) 412 https://doi.org/10.18063/ijb.740