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Dhakshinamoorthy Sundaramurthi, Sakandar Rauf and Charlotte A. E. Hauser
mechanical properties limits its suitability in bioprint- tion (crystallization of β sheets). Silk fibroin physi-
ing. Gelatin is a denatured form of collagen and hence cally blended with gelatin will improve the ink flow.
has less tertiary structures [83] . The presence of RGD Also, gelatin can incorporate RGD motifs in silk fi-
motifs in gelatin makes it a suitable candidate for a broin which in turn improve the cellular compatibility.
broad range of applications in tissue engineering [84] . Silk fibroin-gelatin scaffolds promote the redifferen-
Gelatin usually exists in the coiled form at 40° C tiation of chondrocytes and multilineage differentia-
and when cooled it can regain triple helix form [83] . tion of human nasal inferior turbinate tissue derived
This transition property is necessary for a bioink to mesenchymal cells [91,92] .
improve the integrity of the constructs post-print. Ge-
latin was blended with methacrylamide to obtain gela- 5.2 Synthetic Polymers
tinmethacrylamide, a photoactive polymer, that can Natural polymers containing cell adhesion motifs have
form stable 3D structures after UV crosslinking [85] . been used to mimic the native extracellular matrix.
This cross-linking stabilizes the construct post-print [86] . Synthetic polymers offer biocompatibility, strong me-
Various chemical functionalization methods have been chanical properties, degradation profile and allow
employed to control the gelling behavior, cross-link- chemical modification to alter the structure and func-
ing behavior, and viscosity of gelatin in solution. tion of the polymer. The ease of processability has
Though gelatin bioink has shown cellular compatibil- made synthetic polymers as a good candidate for bio-
ity, its highly viscous nature limits its applications in printing applications. Bioactive molecules can be in-
bioprinting. corporated to modify these polymers to induce specif-
(3) Hyaluronic acid ic cellular responses [93] . Some of the synthetic poly-
Hyaluronic acid is a linear polysaccharide made of mers used for bioprinting are discussed as follows.
(β-1,3) β-1,4-linked D-glucuronic acid and N-acetyl- (1) Poly(lactide-co-glycolide) (PLGA)
D-glucosamine disaccharides. It is a viscoelastic, bio- PLGA is a copolymer of lactide and glycolide,
degradable and highly biocompatible polymer. Hya- synthesized via ring opening polymerization mechan-
luronic acid is an interesting candidate for bioprinting, ism. It can be synthesized with different copolymer
but its high hydrophilicity limits its application [87] . ratios, and their degradation rates can be controlled.
Chemical cross-linking methods and derivatization of PLGA has been successfully used as bioink to create
hyaluronic acid with hydrophobic side chains have 3D vascular networks. Human umbilical vein endo-
been attempted to reduce hydrophilicity but still not thelial cells (HUVECs) were deposited on the PLGA
successful in bioprinting [87] . Blending hyaluronic acid based biopaper by using biological laser printing me-
with some photocrosslinkable materials such as Dex- thod [94] . 3D tissues were created by stacking the PLGA
HEMA have been shown to improve the cell viability sheets containing HUVECs [94] . Hydrolytic degradation
of chondrocytes [88] . Further, the physical blends of behavior and fast solvent evaporation of PLGA makes
gelatin-alginate [89] , fibrin-collagen [67] , gelatin-hyalur- it a promising bioink for printing various types of tissue
onic acid [88] have also been used as bioinks. structures.
(4) Silk fibroin (2) Poly(ethylene glycol) (PEG)
Silkworm (Bombyx mori) derived fibrous protein Poly(ethylene glycol) (PEG) is a biocompatible and
called silk fibroin is an amphiphilic block copolymer. a hydrophilic polymer used for various biomedical
The main heavy chain of silk fibroin has twelve re- applications. PEG has been employed in various ap-
peating domains with frequent occurrence of G-X-G- plications such as nanoparticle coating to prevent ag-
X-G-X where G is glycine and X may be serine or gregation, bioink for printing scaffolds and encapsula-
alanine. The repeating units are separated by hydro- tion of cells [42] . It is soluble in water but require che-
philic peptides that have eleven amorphous regions. mical modification to form gels. Moreover, tissue en-
Silk fibroin has high tensile property and also good gineered scaffolds were surface modified with PEG to
biocompatibility [90] . The addition of weak acids such improve cellular compatibility and protein adsorp-
as methanol will cause a transition of molecular or- tion [42] . This polymer can easily form physical or che-
ganization between random coils to aggregation and mical crosslinked networks after acrylation. Photoini-
β-sheets formation. This property makes silk fibroin tiators are employed to crosslink PEG under UV ex-
suitable for bioprinting [90] . However, printing silk fi- posure. Acrylated PEG has been used as bioink to print
broin alone can cause needle clogging due to aggrega- vascular grafts [42] . PEG blended with dimethacrylate
International Journal of Bioprinting (2016)–Volume 2, Issue 2 17

