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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

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