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International Journal of Bioprinting                                   3D bioprinting in otorhinolaryngology




            optimize the bioprinting quality.  Hybrid bioprinting   term toxicological and mechanical studies.  Moreover,
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            can also be used to effectively improve droplet-based 3D   more studies are warranted to study the relationship and
            bioprinting. Xu et al. designed a hybrid inkjet bioprinting/  mechanisms of laser parameters. In this regard, laser-based
            electrospinning system to fabricate cartilage tissues. In   bioprinting is not as mature as the other technologies
            this system, electrospinning polycaprolactone (PCL) fibers   and will require significant developments prior to its
            were fabricated, and rabbit elastic chondrocytes suspended   widespread application. 56
            in  a  fibrin-collagen  hydrogel  were  printed  for  cartilage   Table 1 summarizes the advantages and disadvantages
            construction. Compared with single bioprinting, the   of the aforementioned 3D bioprinting techniques (i.e.,
            cartilages fabricated using the hybrid inkjet bioprinting/  extrusion-based, droplet-based, and laser-based).
            electrospinning system had better biological and physical
            properties.                                        3. Bioinks
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            2.3. Laser-based 3D bioprinting                    Bioinks are essential for 3D bioprinting and can be defined
            Laser-based 3D bioprinting uses a laser in a nozzle-free   as a formula suitable for cells processed by automated
            design to generate transient microbubbles that expand and   biofabrication techniques that may also contain bioactive
            rupture to release the bioink. 45,46  The bioprinting rate can   ingredients and biological materials. Generally, bioinks
            be adjusted by the laser frequency, as well as the type and   consist of a hydrogel solution (natural or synthetic)
            concentration of the photoinitiator. 47,48  Laser-based 3D   and cellular components. 58,59  A variety of natural and
            bioprinting prevents direct contact between the bioink and   synthetic hydrogel materials have been developed via
            bioprinting device, and this prevents damage to the cells   crosslinking and are increasingly being designed to reflect
            and other components, leading to a high cell survival rate.   the natural extracellular matrix and facilitate their use as
            Additionally, laser-based 3D bioprinting does not result   3D structures to support tissue regeneration. Hydrogels
            in pore obstructions and has a wider range of applicable   have a high water content and the ability to suspend cells.
            viscosity, indicating its compatibility with almost all   Consequently, they can be engineered into an extracellular
            types  of bioink and applicability for bioprinting various   matrix microenvironment for cell encapsulation.
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            structures. 49,50  Xiong et al. constructed Y-shaped and   Related experiments have demonstrated that hydrogel
            straight tubes using 8% alginate solution and 2% alginate   biomaterials, such as hyaluronic acid (HA), can produce
            mouse fibroblast suspension in a laser-based bioprinting   barriers and  protect the load  cell from the  stress  of  the
            system, and the survival rate of the printed laryngeal cells   bioprinting process to ensure high cell survival rates and
            was more than 60%.  Laser-based bioprinting features   activity levels.  Hydrogels have many other  advantages,
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            a high resolution, which is essential for bioprinting   such as specific cell-binding sites, high biocompatibility,
            precise structures in experimental manufacturing,   and good degradability, making them the primary
            including microstructures and microdevices. Serien et   biomaterials used in 3D bioprinting and, in particular,
            al.  fabricated  complex  bionic  3D  microenvironments   in otorhinolaryngology-related 3D bioprinting. 62,63  The
            and biochips from pure blood albumin microstructures   commonly used hydrogel materials include alginate, gelatin,
            using a photo-activator.  Kingsley et al. used laser   collagen, fibrin, HA, gelling glue, agarose, chitosan (CS),
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            direct-write (LDW) bioprinting to produce multicellular   silk, decellularized extracellular matrix, and polyethylene
            tumor spheroids (MCTSs) and embryoid bodies (EBs)   glycol. An increasing number of experiments are exploring
            models. They adjusted the size of microbeads using the   strategies to improve the performance of hydrogel-based
            beam  diameter and  were  able  to  accurately  control  the   bioink formulations. 64-67  In this section, we discuss several
            cellular spatial location.  Other experiments have also   hydrogel materials and cell components commonly used
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            successfully confirmed the construction of complex   in otorhinolaryngology.
            in vitro products using laser-based 3D bioprinting,
            suggesting its integration into tissue engineering.  Despite   3.1. Protein-based hydrogels
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            the advantages of laser-based 3D bioprinting (e.g., high   For otorhinolaryngology-related tissue bioprinting, the
            resolution and intensity), the cost is high and the process   stability of the structure determines the integrity and
            is more complex than the other bioprinting techniques.    survival of the transplanted tissue. Hence, the structure
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            Besides that, laser-based bioprinting could potentially be   should be tissue-matched physically and chemically, as well
            carcinogenic. For example, the photosensitive resin used   as  having excellent  biocompatibility with the  biological
            in the light-curing process is a potential carcinogen and   environment. Notably, collagen is the main structural
            health hazard.  Another drawback is the poor long-term   protein  of  the  mammalian  extracellular  matrix  and  is
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            stability of photosensitive materials, and the application of   widely used in 3D bioprinting.  Beketov et al. designed
            this technology in human clinical trials will require long-  a bioink composed of 4% collagen and chondrocytes and

            Volume 10 Issue 4 (2024)                        31                                doi: 10.36922/ijb.3006
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