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International Journal of Bioprinting                   Multi-scale vascularization strategy for 3D-bioprinted tissue



            in the tissue fabricated in this study were formed radially   Funding acquisition: Won-Soo Yun
            from the diffusion channel created by modifying the cell   Investigation: Jae-Hun Kim, Minji Park
            culture insert; therefore, interconnecting each vasculature   Methodology: Songwan Jin, Jae-Hun Kim
            is difficult. A recent report showed that the direction of a   Project administration: Songwan Jin
            sprouted capillary can be controlled by engineering the   Writing – original draft: Jae-Hun Kim, Minji Park
            stiffness of the bioink . Upon combining this approach   Writing – review & editing: Songwan Jin, Won-Soo Yun,
                              [20]
            with the strategy suggested in this research, a multi-scale   Jin-Hyung Shim
            vascular network-like native tissue can be built in the
            bioprinted tissue. Another challenge is the formation of   Ethics approval and consent to participate
            large-scale blood vessels in the tissue for anastomosis.
            In organ transplantation, a large-scale blood vessel is   Not applicable.
            sometimes necessary to connect with other blood vessels
            in the body. Szklanny et al.  reported a tissue fabrication   Consent for publication
                                 [21]
            method using large-scale blood vessels for tissue flaps. This   Not applicable.
            method can be applied together with our vascularization
            strategy for fabricating a tissue with a hierarchical blood   Availability of data
            vessel structure and a large-mid-small-sized structure.
                                                               Data can be obtained from the corresponding author upon
            5. Conclusion                                      reasonable request.

            This study successfully demonstrated an advanced multi-  References
            scale vascularization  strategy  through a  combination  of
            pre-set extrusion bioprinting and endothelial sprouting   1.   Ng WL, Chua CK, Shen Y-F, 2019, Print me an organ! Why
            by biochemical factors. Using this strategy, we successfully   we are not there yet. Prog Polym Sci, 97:101145.
            fabricated bioprinted tissue embedded with hierarchical   https://doi.org/10.1016/j.progpolymsci.2019.101145
            vascular  structures  consisting  of  mid-scale  vasculatures
            and capillary branches. In particular, vasculatures, with a   2.   Griffith BP, Goerlich CE, Singh AK, et al., 2022, Genetically
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            extrusion bioprinting technique, and capillary branches, with   Engl J Med, 387(1):35–44.
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            sprouting, were able to effectively deliver materials,   3.   Cohen BP, Bernstein JL, Morrison KA, et al., 2018, Tissue
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                                                                  https://doi.org/10.1371/journal.pone.0202356
            Acknowledgments                                    4.   Uygun BE, Soto-Gutierrez A, Yagi H, et al., 2010, Organ
                                                                  reengineering through development of a transplantable
            None.                                                 recellularized liver graft using decellularized liver matrix.
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            Funding                                               https://doi.org/10.1038/nm.2170

            This research was supported by a National Research   5.   Di Piazza E, Pandolfi E, Cacciotti I, et al., 2021, Bioprinting
            Foundation of Korea (NRF) grant funded by the Ministry of   technology in skin, heart, pancreas and cartilage tissues:
            Education (NRF-2017R1A6A1A03015562) and Ministry      Progress and challenges in clinical practice. Int J Environ Res
            of Science and ICT (NRF-2020R1A2B5B01002716).         Public Health, 18(20):10806.
                                                                  https://doi.org/10.3390/ijerph182010806
            Conflict of interest
                                                               6.   Miri AK, Khalilpour A, Cecen B, et al., 2019, Multiscale
            The authors declare no conflicts of interest.         bioprinting of vascularized models.  Biomaterials, 198:
                                                                  204–216.
            Author contributions                                  https://doi.org/10.1016/j.biomaterials.2018.08.006

            Conceptualization: Songwan Jin                     7.   van Duinen V, Stam W, Mulder E, et al., 2020, Robust and
            Formal analysis: Songwan Jin, Jae-Hun Kim             scalable angiogenesis assay of perfused 3D human iPSC-


            Volume 9 Issue 4 (2023)                        172                         https://doi.org/10.18063/ijb.726
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