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International Journal of Bioprinting Hydrogels for 3D bioprinting

a sacrificial material for constructing hollow blood vessel 3.3.1. Modified gelatin
channels to simulate bionic blood vessels in the bioprinting Among the numerous modified hydrogels, modified
of tissue engineering [82,83] . Karyappa et al. used a low- gelatin is one of the most widely used modified natural
[84]
viscosity, commercial polysiloxane resin (Ecoflex 10) hydrogels, namely methacryloyl gelatin. Gelatin is a
as shell inks in conjunction with a coaxially extruded commonly used soft tissue repair material, but gelatin only
core fluid (Pluronic F127) for core–shell 3D printing in physically crosslinks at low temperatures to form a hydrogel
a Bingham plastic microparticle gels (ethanol gel). They network and dissolves at 37°C. Therefore, after methacrylic
wisely selected appropriate rheological properties and flow anhydride modified gelatin, it becomes a photosensitive
rates of the three phases, which allowed the formation of hydrogel material triggered by a photoinitiator. The
droplets composed of a core liquid distributed along the reaction time under UV-visible light is 3 to 5 s, and the
printed filament. The versatility of eCS3DP provides a properties are stable. So far, the most widespread printing
simple way to fabricate 3D structures of a soft elastomeric method for gelatin methacrylate (GelMA) hydrogels is
matrix with embedded channels and paves the way for extrusion bioprinting [85,86] .
future fabrication of 3D structures with internal channels.
Although GelMA can form a chemical bonding
Compared to natural polymer-based hydrogels, hydrogel under UV light with the help of a photoinitiator,
although some synthetic polymer-based hydrogels have direct bioprinting is still somewhat difficult, because the
been widely used in tissue engineering and regenerative shear-thinning behavior at 37°C is insufficient, and the
medicine, their safety and long-term effects still need to viscosity is not enough to support printing, resulting in
be more rigorously evaluated and monitored. In addition, a low resolution . The commonly used solution is to
[87]
the preparation of synthetic polymer-based hydrogels is compound the GelMA hydrogel with other biological
more complex, requiring sophisticated instrumentation materials to improve its defects. Rastin et al. summarized
[22]
and technical support, and is therefore more costly, four different additives, i.e., polymers, fillers, particles, and
limiting its popularity in large-scale applications. However, fibers, which are often introduced into hydrogels to improve
synthetic polymer-based hydrogels also have some unique hydrogel bioinks with different functions. They added
advantages, e.g., they are often highly tunable, and their methylcellulose (MC), a water-soluble polymer, to improve
physicochemical properties can be controlled by adjusting the printability of GelMA. At the same time, GelMA
parameters such as composition, concentration, and degree hydrogel as a tackifier improves the thixotropic behavior
of crosslinking of the material to give different mechanical of MC during the printing process and slows down the
properties, pore structure, and bioactivity . In addition, degradation rate of MC. Figure 2B(a) shows the complete
[22]
synthetic polymer-based hydrogels can be precisely process of printing and UV crosslinking. The rheological
positioned and molded by 3D printing technology, allowing properties and mechanical properties of different ratios
the preparation of tissue engineering constructs with of MC/GelMA hydrogels are shown in Figure 2B(b). The
complex structures and fine morphology, achieving high addition of MC makes the hydrogel’s stress larger, and the
3D printing accuracy [39,77] . Researchers can also provide compression modulus (15 ± 1.2 KPa) of MC8/GelMA5
cell adhesion sites for scaffolds through a customized is three time higher than pure GelMA5 (4.5 ± 0.2 KPa).
approach to promote cell growth and differentiation, Moreover, the increase in GelMA composition also
contributing to tissue regeneration and repair. Overall, increases the compressive modulus. Pure GelMA hydrogel
finding some natural polymer-based hydrogel bioinks with extrusion is a droplet whose viscosity is too low for
better biocompatibility and lower immunogenicity, as well printing. After adding MC, at a lower shear rate, different
as reducing printing and fabrication costs, are top priorities ratios of MC/GelMA bioinks have higher shape fidelity
for the future of natural polymer-based hydrogels as 3D and viscosity after printing; at a higher shear rate, there is
bioprinting inks for wider use in tissue engineering and a similar viscosity, which shows shear thinning. Compared
regenerative medicine. with pure MC, the addition of GelMA will increase the
pressure during extrusion printing and improve the
3.3. Modified natural hydrogel resolution of printing. However, when the concentration
The modified natural hydrogels are obtained by chemically of GelMA is very high, the yield stress will be higher, and
modifying the functional groups. The modified hydrogels the hydraulic pressure of the extrusion printing will also
still maintain the excellent biocompatibility of natural be higher. The GelMA hydrogel becomes a solid filament
hydrogels and also has properties such as tunable and will maintain this structure that is difficult for the
mechanical strength. Generally, natural hydrogels are crosslinking reaction. Therefore, they chose MC8/GelMA5
modified with methacrylic anhydride reagents. Such as the optimal formulation for printing a four-layer grid
materials include gelatin, chitosan, and silk fibroin. structure, and 100-layer cylindrical and hexagonal two-

Volume 9 Issue 5 (2023) 215 https://doi.org/10.18063/ijb.759