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International Journal of Bioprinting                                   3D bioprinting in otorhinolaryngology



















                                     Figure 1. 3D bioprinting techniques (adapted with permission from ref. ).
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            membrane rupture and cell death.  In addition, with the   2.2. Droplet-based 3D bioprinting
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            extrusion injection method, bioinks can block the nozzle;   Droplet-based 3D bioprinting can be divided into inkjet,
            however, this is not a concern when using nozzle-free laser-  acoustic droplet, and microvalve droplet bioprinting.
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            based 3D bioprinting. In comparison with the other two   Inkjet bioprinting uses the gravitational, thermal, and
            commonly used bioprinting techniques (i.e., droplet-based   electrostatic mechanics of bioinks to eject droplets onto
            bioprinting and laser-based bioprinting), increasing the   a receiving substrate.  Acoustic droplet bioprinting
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            speed and throughput of extrusion-based 3D bioprinting   uses gentle sound waves to eject droplets from an open
            results in low-resolution printed models. 26,29  Several   pool, whereas microvalve droplet bioprinting uses an
            methods have been proposed to correct these shortcomings   electromechanical valve to pressurize the bioink, creating
            and enhance the bioprinting accuracy and efficiency. Wang   enough pressure to overcome the surface pressure and
            et al. monitored the bioprinting process using optical   produce droplets. 34,35  Owing to the non-contact nature
            coherence  tomography (OCT)  and  constructed  a  multi-  of the droplet-based 3D bioprinting techniques, harmful
            material static model and time-related control model for   stress is avoided, making these methods convenient for in
            extrusion-based multi-material bioprinting. This model   situ bioprinting.  Further advantages of droplet-based 3D
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            effectively reduced the time required for bioprinting and   bioprinting include a low cost, faster bioprinting speed, high
            identified a relationship between fiber size and other   repeatability, resolution, and cell viability. 36-39  However,
            parameters.  The establishment of this model created   droplet-based 3D bioprinting has many disadvantages.
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            an effective and fast error identification and correction   Bioink fragments can cause blockages in the orifices,
            process, by which the disadvantages of conventional   and consequently, the selected bioink must have a low
            extrusion-based 3D bioprinting can be minimized and the   viscosity (<10 mPa·s) and cell density (<10  cells/mL). 40,41
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            advantages exploited accordingly. Brion et al. developed   The acoustic droplet jet bioprinting process may introduce
            a multi-head neural network that could automatically   interfering factors that disrupt process control, and sound
            establish  a bioprinting  database  using  data  acquisition   waves could fail to spray droplets of viscous bioinks with
            and annotation. The trained neural network identified   high cell concentrations. Controlled by the valve opening
            the most recent bioprinting parameters and monitored   time of pressure, the microvalve bioprinter is more suitable
            and corrected various bioprinting errors to optimize the   for high viscous materials, but the bioprinting of high-
            bioprinting process.  Extrusion-based 3D bioprinting   resolution bioinks is relatively poor.
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            can also be combined with multi-materials, coaxial,
            and micro-bioprinting techniques. These combinations   However, several methods could be used to address these
            simultaneously improve bioink printability, bioprinting   disadvantages and improve the bioprinting process. Zhang
            speed, and model resolution. Bagnol et al. explored the   et al. proposed a novel hybrid machine-learning method
            combination of coaxial bioprinting and micro-extrusion-  for exploring the bioprinting space using Latin hypercube
            based 3D bioprinting. Coaxial printed calcium phosphate   sampling. Their results revealed a causal relationship
            (CaP) cement with water and ethanol mixtures was   between the morphology of the deposited droplets and the
            used to refine the coaxial bioprinting and increase shape   characteristics of printed lines using K-means clustering.
            stabilities.  With the integration of multidisciplinary   These data ensured bioprinting quality in the design
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            technologies, errors have been effectively reduced.   space  using  support  vector  machines. Gaussian process
            Nonetheless, future developments are expected to enhance   regression was  adopted  to  establish  the  geometrical
            the application value of extrusion-based 3D bioprinting.  characteristics of the droplets in the process model and


            Volume 10 Issue 4 (2024)                        30                                doi: 10.36922/ijb.3006
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