Page 219 - IJB-9-5

International Journal of Bioprinting Hydrogels for 3D bioprinting

spatial arrangement of cells and formation of spheroids in polyethylene glycol (PEG), etc. have been modified by
a short period of time using magnetic interactions, which combining methacrylate. Remarkable hydrogel materials
facilitates the cells to form their own 3D microenvironment are limited to the application of light-based 3D bioprinting
and ECM, and promotes their mutual responses. Moreover, technologies [39-41] . Nevertheless, as a key factor of light-
the magnetic nanoparticles used in this study can curing printing, obtaining light-curing hydrogel materials
support cell proliferation and regulate their metabolism is an important research direction, and it is also a challenge
without triggering inflammation and oxidative stress. It we must face in the future simultaneously.
was found that extrusion-based bioprinting is not only
simple to operate and low cost, but also suitable for most 3. Polymer-based hydrogel bioink
biomaterials, making this method the most widely applied According to the sources and properties of hydrogels
in 3D bioprinting. However, the preparation of non- generally used in 3D bioprinting, they can be divided into
synthetic bioinks with rheology and biocompatibility is three main categories: natural polymer-based hydrogels,
also one of the main challenges of extrusion bioprinting . synthetic hydrogels, and modified natural hydrogels.
[31]
In addition to the above-mentioned technologies, 3.1. Natural polymer-based hydrogels
photocrosslinking-based 3D bioprinting technologies are Natural hydrogels can more effectively mimic the
also gradually being adopted for extensive use, including biopolymers that exist in natural ECM, which have the
stereolithography, two-photon polymerization (2PP), and advantages of good biocompatibility, easy biodegradability,
digital light processing (DLP) [32-34] (Figure 1B–D). Besides, and low toxicity . Natural hydrogels include sodium
[33]
another approach of stereolithography is the digital alginate (SA), gelatin, silk fibrin (SF), collagen, fibrin, and
micromirror device (DMD) bioprinting (Figure 1E) [35,36] . hyaluronic acid [42-44] . Here, we mainly review the natural
Ying et al. used this technique for bioprinting polymer hydrogels that are most used in recent years.
[35]
GelMA-PEO emulsion bioinks. They bioprinted the
cell-filled construct using a pre-designed serpentine 3.1.1. Sodium alginate
pattern, while the uncrosslinked bioink along with PEO In 3D bioprinting, SA is one of the most studied and broadly
droplets was washed off with PBS immediately after applied cell-loaded hydrogel materials. Because it can be
bioprinting. DMD bioprinting is on the basis of layer- gelled through simple ionic crosslinking and has good
by-layer photocrosslinking of the bioink in the reservoir, biocompatibility, it has better mechanical properties than
which avoids subjecting the cells to the shear stress other protein hydrogels . However, the disadvantages of
[45]
associated with the extrusion process that leads to cell SA include poor printing performance, low mechanical
fragmentation . However, DMD bioprinting technology strength, and poor structural stability of printing, and
[37]
also has some minor drawbacks, such as its layer-by- it cannot promote cell proliferation and differentiation.
layer photocrosslinking technology, which may inevitably Increasing the viscosity of pure SA can meet the conditions
reduce printing efficiency. To solve the problem, Kelly such as the rheology of printing, but the fidelity of shape is
et al. proposed the computed axial lithography (CAL) too bad after printing . Therefore, the current researches
[38]
[46]
technique in a volume accumulation method for target mainly focus on the composite of SA and other biological
formation through photopolymerization, which is several materials or the modification of SA and other materials [47-49] .
ranks of magnitude faster than layer-by-layer printing When mixing with other materials, it is generally considered
(Figure 1F). The technique gives them the ability to that the optimal concentration range of SA is 1% to 5%.
synthesize 3D structures of arbitrary geometry through When the concentration is lower than 1%, although it is
photopolymerization. The CAL method presents several easy to dissolve and mix, the shape fidelity becomes very
strengths over traditional layer-based printing methods; bad after printing, and it can easily collapse. When the
for example, they can be used for circumventing support concentration is higher than 5%, the SA solution decreases
structures because it can print highly viscous liquids cell viability, which is too viscous to be used as a bioink
or even solids. It is also possible to use this technology for extrusion printing. The concentration of the commonly
to print 3D structures around pre-existing solid parts. used crosslinking agent calcium chloride is generally
In addition, CAL technology allows for larger print 0.5 M . Sodium alginate-gelatin (SA-Gel) hydrogels
[31]
volumes along with faster print speeds. Compared to have been extensively applied for extrusion bioprinting,
traditional extrusion-based bioprinting, the light-curing which is the most common mixture form. Because the
printing method has shown many advantages and will optimization of bioinks is essential for printing and cell
play a crucial role in the development of bioprinting. At adhesion and survival, many researchers have made some
present, particularly several natural and synthetic hydrogel attempts to optimize the SA-Gel hydrogels. Liu et al.
[50]
polymers such as gelatin, chitosan, hyaluronic acid (HA), investigated the effect of different concentrations of nano-

Volume 9 Issue 5 (2023) 211 https://doi.org/10.18063/ijb.759