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International Journal of Bioprinting Extrusion-based biomaterial inks
it the first choice for cell embedding, and it is widely GelMA hydrogels, thereby forming strong interface
used in extrusion-based bioprinting to promote the rapid bonding between different hydrogels and improving the
formation of 3D structures. Alginate is biologically inert adhesion of printed layers . Carrageenan hydrogels are
[77]
with a low cell adhesion rate, and its corresponding calcium brittle and the mechanical stabilities are poor, resulting in
ion crosslinking reagents will adversely affect cell viability. the printed constructs structure unstable. To overcome this
However, alginate can be chemically modified by adding drawback, the polymer backbone is chemically modified.
cell adhesion ligands to promote cell adhesion, stretching, For example, methacrylated Kappa-carrageenan combined
and proliferation [150] . Benefited from its rapid hydrogel with NIH-3T3 cells was used as co-axial printing bioinks at
gelation rate, alginate is often combined with other room temperature, and the use of UV crosslinked hydrogel
hydrogels, such as gelatin , collagen [151] , Matrigel , and resulted in latticed constructs with high mechanical
[30]
[36]
Pluronic [107] , to improve construct stability. Another main strength .
[78]
application of alginate is to directly fabricate hollow tubes
by coaxial printing [25,27] so as to construct vascularized 3.2.4. Chitosan
tissue for perfusion culture. Chitosan, a linear polysaccharide composed of
D-glucuronic acid and N-acetyl-D-glucosamine, is
3.2.2. Gellan gum obtained from deacetylation of chitin. Chitosan powders
Gellan gum is a natural polysaccharide gum obtained by are generally soluble at acidic pH lower than 6, and the
the fermentation process of microorganism. Gellan gum, dissolved positively charged chitosan solution has high
an anionic polysaccharide, like alginate, is capable of viscosity and shear-rate shinning behavior for extrusion-
forming gels in the presence of Ca . Gellan gum is also based printing . The mechanical integrity of chitosan
2+
[59]
used in co-axial bioprinting owing to the rapid crosslinking hydrogel is weak; therefore, it is hardly used as biomaterial
mechanism . The addition of gellan gum to hydrogels, ink alone. Blending alginate with chitosan can improve
[72]
like GelMA , can significantly increase the viscosity due the compression of printed constructs . Chitosan has
[73]
[58]
to the ionic crosslinking. In addition to the low production hemostasis, anti-bacterial, and antifungal activities, so it
cost, gellan gum can achieve mechanical strength similar to has great potential to be used in bioprinting skin tissue.
that of gelatin at lower concentrations, which encourages A study reported that chitosan/PEG composite hydrogel-
increased use of the material . On the other hand, the encapsulated keratinocytes and dermal fibroblasts were
[72]
gel brittleness is also similar to gelatin, which restricts printed layer by layer to construct skin tissues for potential
structural stability of printed constructs. The mechanical skin regeneration . Although chitosan shows structural
[54]
properties of gellan gum can be modified by blending it characteristics similar to those of hyaluronic acid, it is not
with other biomaterial inks, such as alginate , PEGDA , conducive to cell adhesion and proliferation because it
[69]
[70]
and even nanoparticles, such as graphene oxide . lacks cell binding domains. A study reported that blending
[71]
gelatin with chitosan formed physical polyelectrolyte
3.2.3. Carrageenan hydrogel at pH 6.3, which was extruded at room
Carrageenan, a sulfated polysaccharide extracted from temperature to fabricate 3D constructs with high shape
red algae, is composed of repeated galactose units, fidelity . Neonatal human foreskin fibroblasts that are
[57]
similar to natural glycosaminoglycans. Depending on the seeded onto the polyelectrolyte hydrogel could attach and
sulfate content, source of extraction and solubility, the proliferate better compared to the pure chitosan hydrogel.
carrageenan can be conventionally categorized into six
basic forms: Kappa, Iota, Lambda, Mu, Nu, and Theta [152] . 3.2.5. Silk fibroin
Kappa-carrageenan and Iota-carrageenan can perform Silk fibroin, a natural fibrous protein polymer, is commonly
thermogelation, that is, the polymer can form gels at low derived from silkworm silk and spider silk. Silk fibroin
temperature. Blending carrageenan with other hydrogels usually lacks cell binding domains ; however, silk from
[18]
can adjust rheological property due to the high viscosity. Philosamia ricini has the intrinsic presence of the cell-
The addition of carrageenan to alginate hydrogels could binding RGD tripeptide . The sol–gel transition of silk is
[82]
increase rheological properties, such as shear shinning, the change of secondary conformation from random coil
thixotropic behavior, and viscoelasticity, which improve the to β-sheet structure. Silk solution can form gel under the
printability and structure fidelity of printed constructs . action of shear force. Therefore, silk may cause frequent
[50]
Carrageenans have negatively charged carboxyl and sulfate nozzle clogging when it is used as biomaterial ink alone .
[82]
groups, which result in gelation through ionic crosslinking Blending silk with other polymers, such as gelatin and
[82]
with specific cations, such as Ca and K . Due to the PEG , can improve injectability in the self-supporting
2+
[68]
+
oppositely charged performance of GelMA, polyelectrolyte printing process. The mechanical property of silk fibroin
complexes are formed between Kappa-carrageenan and is poor under physiological condition and can be easily
Volume 9 Issue 2 (2023) 11 https://doi.org/10.18063/ijb.v9i2.649

