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International Journal of Bioprinting Hydrogels for 3D bioprinting
is difficult to use them alone as bioprinting inks, so many chitosan affects the stability of the scaffolds, they first tested
researchers introduced exogenous crosslinking methods the high-molecular-weight and low-molecular-weight
or mixed natural polymer-based hydrogels with other chitosan materials. Then, the ratio of the materials was
polymers or printed them with other structural support optimized. Under low ratios (1:5 and 1:10) and high ratios
materials, and the hydrogels can be tissue-specific adjusted (1:10 and 1:15), the results showed that high-molecular-
to the specific repair site and repair modality. For example, weight chitosan has lower mechanical properties and
genipin crosslinking of gelatin will lead to reduced swelling smaller cell adhesion. However, low-molecular-weight
and increased hardness of gelatin due to the powerful chitosan exhibits a good outcome. In the end, they chose
crosslinking effect of genipin. Therefore, it is more suitable low-molecular-weight chitosan and PEGDA to study the
for the repair of hard areas such as bone tissue. In contrast, optimal ratio, which is 1:7.5.
crosslinking of gelatin with mTG provides gelatin with The bioink of this ratio is suitable for the printing
uniform pore space and higher swelling properties, making of complex shapes. They created a human ear-shaped
it more suitable for repair of soft tissue sites and endowing scaffold that showed interconnected porous structures
it with the ability to load or encapsulate other substances after freeze-drying. Human bone marrow mesenchymal
such as drugs or cytokines. These approaches provide stem cells (hBMSCs) can adhere to the scaffold and
useful assistance for people to use natural polymer-based proliferate. Jia et al. [78] designed a hybrid bioink composed
hydrogels as bioinks for 3D bioprinting in the future. of 4-arm poly (ethylene glycol)-tetraacrylate (PEGTA)
3.2. Synthetic polymer-based hydrogel and other hydrogels combined with a multi-layer coaxial
The most common synthetic hydrogels are alcohols, extrusion system. Through ionic bonding and covalent
acrylates, and their derivatives, such as PEG and PEGDA, photocrosslinking, a highly organized perfusion vascular
polyacrylamide (PAAM), and polyurethane (PU) [39,53,76] . structure is formed. The addition of PEGTA enhances
Besides, Pluronic is also a common sacrificial material. the mechanical properties of the scaffold. Compared
We can process and modify natural hydrogels according with linear PEG molecules, PEGTA scaffold allows better
to requirements. cell growth.
3.2.2. Pluronic
3.2.1. Polyethylene glycol Pluronic, which is the trade name of poloxamer, is a synthetic
PEG has good biocompatibility, non-immunogenicity, and block polymer composed of a hydrophobic polypropylene
non-toxicity, but due to a lack of cell adhesion sites on the oxide (PPO) block and two hydrophilic polyethylene oxide
surface, it cannot provide a suitable growth environment (PEO) blocks. The Pluronic gel is a temperature-sensitive
for cells. Therefore, it is often modified by blending, polymer with reversible gel properties; the gelation
grafting, and interpenetrating with natural polymer temperature of it depends on its type and concentration.
hydrogels to optimize the performance of hydrogels [39,77] . Unlike gelatin and SA hydrogel, Pluronic is liquid at low
PEG and SA can form an interpenetrating network to temperatures (usually 4°C), forms a physical gel at high
stably keep the 3D structure of the hydrogels in the form temperature (37°C), and can be dissolved in deionized
of covalent crosslinking. Different molecular weights of water. Therefore, after printing scaffolds, lowering the
PEG and different crosslinking agents have a tremendous temperature can remove Pluronic smoothly [79-81] .
impact on the elasticity of the hydrogel. The application of
Ca -containing crosslinking agents in PEG-SA hydrogels Pluronic materials show better results in cartilage
2+
can significantly increase its fracture energy. Conversely, tissue engineering. The high concentration of Pluronic can
with the molecular weight of PEG increasing, the length meet the rheological and gelling conditions required for
of the polymer chains also increases, resulting in higher extrusion printing. For example, Müller et al. [80] proposed
tensile properties and higher fracture energy of the a nanostructured method that can meet the performance
hydrogel . PEG is usually used as a light-curing material requirements of Pluronic F127 gels during the entire
[53]
after modification. PEG derivatives are mainly PEG bioprinting process. The pure Pluronic F127 hydrogel
acrylates, which include PEGDA, PEG dimethacrylate cannot culture cells for a long time. But after acrylate
(PEGDMA), and multi-arm PEG acrylates [39,78] . As a modification, a high concentration of Pluronic F127 is used
bioink for 3D bioprinting, a blended solution of chitosan in the printing process, and then it is eluted for chondrocyte
and PEG acrylic hydrogel is a potential candidate material. culture. The results showed that cell viability increased
Morris et al. used chitosan and PEGDA as bioinks to from 62% to 86%. Besides, to improve the mechanical
[39]
print scaffolds through stereolithography technology, and properties of Pluronic F127 hydrogel, a photocrosslinked
its mechanical strength met the requirements of cartilage hyaluronic acid methacrylate (HAMA) is mixed to form a
tissue engineering. Because the molecular weight of stable network structure. Pluronic F127 is usually used as
Volume 9 Issue 5 (2023) 214 https://doi.org/10.18063/ijb.759

