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International Journal of Bioprinting                                   3D bioprinting in otorhinolaryngology




            Table 1. Summary of 3D bioprinting techniques commonly used in otorhinolaryngology and their advantages and disadvantages
             Bioprinting technique                 Advantage              Disadvantage          Reference
             Extrusion-based bioprinting           Wide range of bioprinting   Slow bioprinting speed;   23-32
                                                   materials; low cost; simple   relatively low cell activity
             Pneumatic-based bioprinting           operation and control; high cell   (40%–80%); nozzle clogging;
                                                   density (cell spheroids)  high exposure to stress;
             Piston-based bioprinting                                     relatively low resolution
             Screw-based bioprinting
                                                                                        6
             Droplet-based bioprinting             Low cost; rapid bioprinting   Low cell density (<10  cells/  33-44
                                                   speed; high repeatability; high   mL); nozzle clogging; cell
             Inkjet bioprinting                    resolution; high cell activity (>   damage
             Acoustic droplet bioprinting          85%)
             Microvalve bioprinting
             Laser-based bioprinting               Rapid bioprinting speed; high cell  High cost; complex operation;   45-56
                                                   activity (>95%); high resolution;   rapid gelation; toxic to humans
             Stereolithography (SLA)               wide range of materials; high cell
                                                   activity (>95%)
             Two-photon polymerization (2PP)


            successfully printed tissue scaffolds using extrusion-based   exosomes (exos) were added to GelMA, while the lower
            bioprinting.  The  scaffold  was  implanted  subcutaneously,   scaffold was added with β-tricalcium phosphate (β-TCP).
            and the cartilage  tissue  (containing  homologous  cell   The upper scaffold material had a relatively low elastic
            populations of glycosaminoglycans and type II collagen)   modulus, which induced the differentiation of hUMSCs
            formed within 17 to 40 days. In comparison with lower   into chondrocytes. In contrast, the lower scaffold improved
            concentrations of collagen, the 4% collagen hydrogel   the elastic modulus of the  hydrogel, thereby inducing
            retained a high biocompatibility with improved printability   osteoblast differentiation. Therefore, the modified bilateral
            and mechanical properties (Figure 2A). 68          scaffold could mediate tissue repair with the differentiated
                                                               bone and cartilage and closely restore the tissue to normal.
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               Gelatin  is  produced  by  collagen  denaturation  and  is
            widely used as a biological material, owing to its excellent   Gelatin and its derivatives are commonly used hydrogel
            physical and chemical properties and biocompatibility,   materials and function to maintain good cell activity and
            similar to collagen. Moreover, gelatin can be obtained   support the differentiation and growth of cells in different
            at a low cost and can be easily processed (Figure 2B). 69,70    directions. Additionally, these materials have excellent
            Bedell et al. have reported that gelatin modified the   biocompatibility, degradability, and processability, making
            polymerization of methyl, propylene, and acyl groups   them valuable for the 3D bioprinting process.
            to obtain methacrylate gelatin  (GelMA), which can be   Silk is a natural polymer with high strength, elasticity,
            covalently crosslinked by ultraviolet (UV) light under mild   and low degradation rate  that can provide appropriate
            conditions. The bioprinting process was well-regulated   support for cells until tissue regeneration occurs.  In
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            to retain biological cell activity and mechanical strength.   addition, silk is widely used to address various tissue
            GelMA  could  be  used  in  different  bioprinting  methods   hardness  requirements  in  otorhinolaryngology and
            and for the regeneration of bones and cartilage.  Tang et   features low immunogenicity and biocompatibility. Singh
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            al. loaded cartilage cells into GelMA and fixed them onto   et al. used silk and gelatin to design bioinks and printed
            polylactic acid (PLA) scaffolds to produce a bioactive   human ear structures with good fidelity. Pure silk was
            artificial cartilage for the auricle. The cartilage cells displayed   reportedly weaker at bioprinting temperatures and did
            good proliferation and cell activity, maintained the pinna   not provide sufficient mechanical strength to support 3D
            shape after transplantation, and successfully generated   bioprinting. The addition of gelatin as a leavening agent
            chondrocytes and a matrix. This study demonstrated the   ensured the fidelity of the bioink during bioprinting and
            potential of constructing auricles and their applications   improved the performance of the biomaterial. The mixed
            in clinical transplantation.  Sun et al. also used GelMA to   materials had a more suitable temperature window (25–
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            construct a double-layer porous hydrogel scaffold for tissue   35°C), which provided the right viscosity for bioprinting
            repair. In the upper scaffold, black phosphorus (BP) and   (Figure 2C and D).  This study demonstrated that different
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            human umbilical cord mesenchymal stem cell (hUMSCs)   natural proteins can be used as bioink components, but

            Volume 10 Issue 4 (2024)                        32                                doi: 10.36922/ijb.3006
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