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International Journal of Bioprinting 3D bioprinting of artificial blood vessel
A B
Figure 2. (A) Transduction of mechanical factors and the regulation of stem cell fate . (B) The difference of physical and chemical gelation below the
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thermal gel point and the morphological change of cell with the stiffness of the hydrogel . Figure 2B reproduced from ref. with permission from John
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Wiley and Sons, Inc. (License Number: 5355060311460).
is (-CH -CH -O-), indicating that the material is bioinert derived free radicals . Pure HA is not suitable for direct use
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2
2
and not suitable to be directly used as a bioink . The use as bioink because HA aqueous solutions give viscous shear-
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of dimethacrylate and diacrylate modified PEG (named thinning preparations a neat prevalence of viscous modulus,
as PEGDMA) is possible to improve its performance as implying that no yield stress and no shape retention will
bioink . The PEGDMA could increase the EC adhesion be resulted on printing. Thus, HA is always combined with
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and proliferation after adding GelMA to form complex other hydrogel for use as bioink . There are two methods
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hydrogel . To further improve the properties of the PEG, to use HA as a bioink: (i) Using HA in the form of a single or
4-arm poly (ethylene glycol)-tetra-acrylate (PEGTA) has multiple chemical derivatives as the main constituent and (ii)
been synthesized. The presence of multiple active cross- using HA with natural polymer to enhance the mechanical
linking sites on the PEGTA could increase the strength property of the structure . A HA-g-pHEA-gelatin is created
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and keep the porous structure after cross-linking . by cross-link polymerization of hydroxyethyl acrylate
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Compared with PEGDMA, PEGTA with porous structure (HEA) to HA and then grafting of gelatin-methacryloyl
could promote cell growth and diffusion within the gel and by radical polymerization. With 6 and 8% concentrations
increase the rapid exchange of nutrients. PEGTA, which of methacrylic anhydride, the hydrogel showed excellent
has a low molecular weight (3350 g/mol), could be cleared printability and cellular biocompatibility . Small-diameter
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by the kidneys to ensure biosafety . More importantly, (4.0 mm) and heterogeneous double vascular structure were
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adding 3 – 4% w/v nanosilicates (nSi) into the poly(ethylene made with GelMA, HA, glycerin, and gelatin, together with
glycol)-dithiothreitol could obtain better shear-thinning EC and SMC that construct the inner and outer tissue so as to
characteristics and precision deposition ability during the mimic natural blood vessels and maintain high cell viability
printing process, as shown in Figure 3 . and proliferation .
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3.1.2. Natural hydrogel The normal cell seeding process is divided into two
steps: (i) Printing the 3D hollow structure using a variety
(A) HA of hydrogels and using the sacrificial material to create
HA, which is a major component of ECM, is a linear and the hollow and (ii) seeding the cells on the inner wall .
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non-sulfated glycosaminoglycan consisting of alternating Although this strategy is widely used to manufacture the
units of β-1, 4-D-glucuronic acid, and β-1, 3-n-acetyl-d . arterial blood vessel, another strategy, which relies on the
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HA has good flexibility, biocompatibility, biodegradation, enzymatically digestible photopolymers, has also been
and bio-absorbability, and its high porosity is conducive to used in the same process . HA could be hydrolyzed into
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the exchange of nutrients . With the rich negative charges smaller molecules by hyaluronidase; the special properties
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in its structure, HA can absorb a great deal of water and then are involved in the printing process to control degradation
increase its volume by 1000 times, forming a loose hydration kinetics, which introduce further changes to the geometry of
network that acts as a sieve to control water transport and the implants, rather than dissolving the material completely.
limit the movement of pathogenic plasma proteins and The application of hyaluronidase enables the creation of
protease into the matrix network, thus playing a key role as an hollow structures of any geometry . By applying this
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immune modulator and anti-inflammatory factor . HA also knowledge, Thomas et al. printed vessel mold with EC,
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shows antioxidant effects for its ability to react with oxygen- which demonstrated better cellular viability (28 days).
Volume 9 Issue 4 (2023) 413 https://doi.org/10.18063/ijb.740

