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International Journal of Bioprinting                                   3D bioprinting in otorhinolaryngology




            in PU microspheres, was printed at low temperatures to   Their results demonstrated that chondrogenic bMSCs had
            form scaffolds containing Y27632 microspheres, and   a greater potential for new cartilage formation in the short
            mesenchymal stem cells (MSCs) in the scaffolds were   term.  However, viral transduction is necessary during the
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            observed to migrate and differentiate in vitro. Moreover,   differentiation and proliferation of iPSCs and may have its
            the in vivo experiments revealed that the stent promoted   potential risks. For example, stem cells may be susceptible
            cartilage cell regeneration.  Tallia et al. and Li et al. used   to  insertional  mutations,  tumorigenesis,  and  teratoma
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            an inorganic–organic hybrid of SiO -polytetrahydrofuran/  formation.  Regardless, stem cells are not ideal bioinks
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                                        2
            PCL as a bioink to fabricate a regenerative scaffold for   due to their poor repeatability, incomplete differentiation,
            cartilage using 3D bioprinting. The printed silicone   low quantity, and low usage, thereby warranting further
            network and organic components were combined using   research to enhance cell differentiation and proliferation
            covalent bonds, both of which have similar elasticity, self-  for better application in bioprinting technology. Liang et
            healing ability, and biological activity when used in vivo   al. developed a new extrusion-based bioprinting method
            as tissues. Cartilage differentiation was observed during   with pre-cultured MSCs in hydrogels, supplemented with
            in vitro experiments.  In addition, Park et al. used PCL to   alginate–gelatin–collagen, for use as a cellular aggregating
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            print porous bellows framework and STP mesh. Moreover,   bioink  in  bioprinting.  The  resultant  bioink  displayed
            hNCs and hNTSCs were encapsulated in thermosensitive   enhanced differentiation and proliferation as compared
            3% (w/v) atelocollagen-based hydrogel to print trachea   with  single-cell bioinks,  demonstrating the  potential for
            rings and epithelium, thereby producing trachea structures   complex tissue construction. 104
            (Figure 4B). 96                                       Different mature cell types can be used as bioinks

            3.5. Cells                                         for different structures, depending on the tissue source.
            The cell source used in 3D bioprinting often depends   For example, Gantumur et al. successfully constructed a
            on the  anatomy and function of  the target tissue. In   human nasal-like 3D construct from a bioink formulation
            otorhinolaryngology, cells are divided into stem and   containing mouse 10T1/2 fibroblasts using extrusion-based
            mature cells according to their degree of differentiation and   bioprinting, and the cells of the 3D construct displayed
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            can be used as bioinks alone for bioprinting or combined   excellent stability in vitro.  The success of cell formulations
            with  other  biomaterials.   Stem  cells,  such as  embryonic   has helped to promote 3D bioprinting for the direct
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            stem cells (ESCs), induced pluripotent stem cells (iPSCs),   construction of living tissues, highlighting a significant
            human amniotic fluid stem cells (hAFSCs), and MSCs,   breakthrough in the history of 3D bioprinting. Although
            are often subjected to targeted differentiation to obtain   there is a lack of direct application of cell bioinks in clinical
            bone, cartilage, and other tissue types for use as bioink   implantation, cell bioinks have reported good proliferation
            components. 85,97-99   For example,  human ESC  (hESC)-  and differentiation in vivo, and these bioink formulations
            derived oral neuron progenitor cells (ONPs) were cultured   can potentially stimulate artificial regeneration and solve
            in a hypoxic environment to aggregate into multicellular   common  clinical  problems  related  to  tissue  repair  (e.g.,
            spheres, a polymeric form that facilitates differentiation,   poor cellular regeneration), such as in tracheal cartilages
            transplantation, and prolonged cell survival to optimize   and nerves that become permanently dysfunctional
            their transplantation conditions.  The bioprinting of   upon damage. Current studies use two main methods to
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            inner ear structures using a bioink developed with cell   stimulate artificial regeneration: (i) induce different stem
            spheres may be an alternative to cochlear implants for   cell types to proliferate and differentiate into target tissues,
            treating sensory hearing loss.  Adipose-derived stem   and (ii) use the regenerative ability of the original tissue in
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            cells (ADSCs) have become one of the most popular seed   vitro to restore tissue function. These methods have their
            cells used in 3D cartilage bioprinting because of their   respective advantages and disadvantages. For stem cells,
            high quantity, good proliferative potential, low harvest   it is necessary to limit differentiation and proliferation to
            incidence, and  ethical  advantages.  Researchers  can   prevent  tumor  formation,  but  mature  cells  should  have
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            induce ADSC differentiation to form different cartilage   rapid regenerative abilities. Therefore, future studies
            tissues and construct different bioinks with the addition   should focus on developing better methods to improve the
            of appropriate growth factors  and stimulating  forces.  In   efficiency and outcome of tissue repair.
            one study, researchers designed hydrogel bioinks loaded
            with human ADSCs that exhibited reasonable printability   4. Bioink performance
            and successful differentiation into osteoblasts.  Bae et   An ideal bioink should share similar physical and
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            al. printed a trachea structure by culturing rabbit bone   chemical properties (printability, mechanical properties,
            marrow MSCs (bMSCs) and respiratory epithelial cells   biodegradability, biocompatibility, and biological activity)
            and subsequently differentiated them in different media.   to the structure of interest to ensure that the bioprinted


            Volume 10 Issue 4 (2024)                        37                                doi: 10.36922/ijb.3006
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