Page 168 - IJB-10-3

International Journal of Bioprinting 3D bone: Current & future

(i) Alginate: Alginate is one of the most commonly used by adding or changing different side groups. These
natural polysaccharides as a hydrogel component. groups can be subjected to different crosslinking
Alginate is derived from alginic acid, also called mechanisms, such as ionic, enzymatic, and photo-
algin, which is a polysaccharide naturally produced crosslinking. In contrast, the basic chitosan
by brown algae. Algin is hydrophilic and forms a structure can only be crosslinked via chemical
viscous non-bioactive gel in an aqueous solution that methods. With these modifications, the mechanical
does not provide ligands to the cells for adhesion. properties of chitosan can be improved, broadening
Algin salts formed with sodium and calcium are its applicability. However, chitosan-based hydrogels
called alginates, which are considered an excellent have rapid biodegradation and high cost. To address
hydrogel base for tissue engineering and bioprinting these issues, chitosan is usually mixed with different
when combined with other bioactive components. materials, such as gelatin, collagen, and GelMa.
Alginates can crosslink rapidly and easily with Nonetheless, chitosan-based hydrogels can be used
ionic solutions, most commonly with calcium in DIW, inkjet, LAB, and DLP bioprinting. 63
chloride. Additionally, alginates are low-cost and (v) Collagen: Collagen is an essential organic constituent
have low immunogenicity. However, they have poor of the ECM. Type I collagen is most commonly used
mechanical properties and weak bone conductivity. for hydrogels in 3D bioprinting. Like gelatin, collagen
Alginate-based hydrogels are commonly used with self-assembly is also temperature-dependent,
DIW, inkjet, and LAB bioprinters. 58 occurring at 20–37°C. Higher temperatures result
(ii) Gelatin: Gelatin is a natural protein produced by in faster bonding and less ordered fibers, thereby
the irreversible hydrolysis of collagen extracted affecting the mechanical and functional properties
from the connective tissue of animals. Gelatin is of the construct. When 3D bioprinting with collagen,
commonly reversibly crosslinked by temperature temperature regulation is crucial to standardize the
and has a melting point between 30 and 37°C. properties of collagen and the resultant hydrogel.
Therefore, it is soluble at body temperature, limiting The gelation of collagen is very slow, and collagen
its applications. Likewise, temperature regulation has a low viscosity, indicating that the printed
is crucial when printing with gelatin, and its slow constructs could not maintain their shapes.
gelation makes it challenging to precisely create Additionally, collagen degrades rapidly, complicating
complex 3D structures. Besides that, gelatin has a fast its cultivation after printing. Nonetheless, collagen-
degradation and poor mechanical characteristics. based hydrogels are commonly used in DIW, inkjet,
However, gelatin is inexpensive and has excellent and laser-assisted bioprinters.
biological properties. Therefore, it is the second most (vi) Hyaluronic acid: Hyaluronic acid is a
commonly used hydrogel component after alginate. glycosaminoglycan found in the ECM of several tissue
Gelatin is usually mixed with other materials, such types. Its hydrophilic nature and high molecular
as alginate or collagen, and is used in DIW, inkjet, weight enable the absorption of large amounts of
and LAB printing techniques. 59,60 water, highlighting its excellent biocompatibility and
(iii) GelMA: GelMa is a modified gelatin engineered bioactivity. However, the solubility and mechanical
with methacrylamide and methacrylate groups. properties of hyaluronic acid are weak, thereby
In contrast to gelatin, GelMa is irreversibly photo- requiring chemical modifications (ionic, enzymatic,
crosslinkable by adding photo-initiator groups, thus temperature-based, and photo-crosslinking) to be
preventing gel dissolution at body temperature. effectively used in hydrogels. Hyaluronic acid-based
In addition, the photo-crosslinking process is hydrogels are mainly used in DIW, inkjet, and LAB
fast, and the crosslinked structures are very stable. bioprinting techniques. 64
However, photo-initiators usually bind to blue (vii) Silk: Silk is a natural polyamide extracted from
or UV light, which could damage the cells, and silkworms. Its main ingredients are silk fibroin
GelMA is also more expensive than alginate and and sericin. Due to the structure of the former,
gelatin. GelMA is most often used in DIW, DLP, and silk can absorb mechanical shocks, making it an
electrospun printing. 61,62
extremely resistant material. Besides that, silk has
(iv) Chitosan: Chitosan is a polysaccharide obtained from excellent biocompatibility, low immunotoxicity, and
the deacetylation of chitin by substituting half of the adjustable degradation, highlighting its suitability
acetyl groups with amine groups, thereby making for tissue engineering. However, the crosslinking of
chitosan soluble in acidic solutions. Due to its poor silk alone in a cellular environment is challenging,
mechanical properties, chitosan is usually modified and silk is high-cost. Nonetheless, silk-based

Volume 10 Issue 3 (2024) 160 doi: 10.36922/ijb.2056