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International Journal of Bioprinting                                      Extrusion-based biomaterial inks



            affected by β-sheet structure. Blends  of hydroxy propyl   temperature-sensitive and reversible gelation. Pluronic can
            methyl cellulose of methacrylation and silk fibroin formed   be used to construct a mold loaded with matrix gel [157]  or a
            double network hydrogel, and the fracture strength,   vascular network channel in a 3D structure [9,106,108] .
            breaking  elongation,  and  compressive  reproducibility  of
            printed  constructs  increased  significantly .  Silk  fibroin   3.2.8. PEG
                                              [67]
            solution is also used in freeform fabrication with nanoclay   PEG is often used as pharmaceutic adjuvant. PEG-
            and PEG support bath . Bioprinting of silk fibroin is   based gels can be formed by physical or covalent
                               [66]
                                                                                                          [158]
            more widely used in cartilage tissue engineering.  crosslinking, and used internally with FDA approval  .
                                                               PEGDA is an acrylated derivative of PEG, which can be
            3.2.6. Agrose                                      photopolymerized to form a gel with superior mechanical
            Agrose, a natural polysaccharide, is obtained from the   properties. PEGDA can be easily used to construct 3D
            cell walls of red algae. Agarose solution has a sol–gel   scaffolds in extrusion-based bioprinting. Similar with
            transition in the range from 32°C to 47°C, depending on   Pluronic, synthetic polymer chains do not contain
            the concentration, and physically polymerizes to form a   attachment points that enable interactions with cells,
            gel within seconds . Although agrose hydrogels lack cell   resulting in a lack of biological activity. Therefore, PEG-
                           [40]
            binding sites and thus have limited bioactivity [153] , adding   based gels  are generally  not printed with cells together
            agrose into other polymers can improve print fidelity and   because the cells cannot easily migrate and proliferate on
            stability of printed structure [40,79] . Agrose can also be used   the printed PEGDA scaffolds ; therefore, they are more
                                                                                       [16]
            as sacrificial material to construct hollow channel [81,154] .   likely to be used as carriers for loading bioactive materials
            Besides, agrose can also serve as suspending hydrogel for   to improve mechanical strength for maintaining the 3D
            the freeform fabrication [155] .                   structure [103] . Another method to improve the bioactivity
                                                               of PEG is peptide modification. For example, PEG-based
            3.2.7. Pluronic                                    microgels were modified with the cell adhesive peptide and
            Pluronic is a non-ionic triblock copolymer composed   then printed together with human mesenchymal stem cells
            of  polyoxyethylene-polyoxypropylene-polyoxyethylene.  to form 3D constructs, which support cell spreading and
            Due to the amphiphilicity caused by the hydrophobicity   proliferation [101] .
            of polyoxypropylene and the hydrophilicity of
            polyoxyethylene, it can form soluble micelles as a carrier   3.2.9. Thermoplastic polymer
            of nano drugs for drug delivery. Pluronic is a temperature-  PCL, PLA, and PLGA are all  thermoplastic polymers,
            sensitive polymer and its critical micelle temperature is   which could serve as structural materials and are capable of
            between 22°C and 37°C. It will self-associate and appear   resisting mechanical forces in hybrid constructs, as shown
            gelatinous above this temperature. Pluronic’s shear   in Figure 5. Usually, thermoplastic polymers are deposited
            thinning performance and thixotropic performance are   by hot melt approach at appropriate temperatures
            excellent, and the printing fidelity is extremely high in   (e.g., PCL at 80°C [111] , PLA at 200°C , and PLGA at
                                                                                              [45]
            extrusion-based  bioprinting.  However,  it  is  biologically   110°C [117] ) to fabricate mechanical  scaffolds, then cell-
            inert with a low cell adhesion rate, and cannot be degraded   laden hydrogels are printed and deposited alongside the
            by enzymes. Its printed cell activity is even as low as 50%   scaffold filaments [117]  or injected into the scaffolds pores .
                                                                                                           [45]
            when it is used as a biomaterial ink alone [156] . Pluronic is   Thermoplastic polymers can also be dissolved in organic
            often used as a sacrificial material, that is, it is dissolved   solvents for preparing extrudable ink by blending with
            at low temperature after printing since it can perform   other hydrogels [115,116] . For example, PLGA was dissolved
















            Figure 5. Thermoplastic polymers for extrusion-based bioprinting. (a) Cell-laden hydrogels are printed alongside the scaffold filaments. (b) Cell-laden
            hydrogels are injected into scaffolds pore. (c) Blending of cell-laden hydrogel and polymer organic solution. (d) Thermoplastic polymers are added into
            cell-laden hydrogel in microspheres form.


            Volume 9 Issue 2 (2023)                         12                      https://doi.org/10.18063/ijb.v9i2.649
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