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





























































            Figure 2. Demonstration of pre-set extrusion bioprinting technique as the fabrication method for mid-scale vasculature-embedded tissue. (A) Changes of
            lumen diameter in bioprinted tissue with alginate concentration (diameter of core region: 3.5 mm, n = 30). (B) Influence of geometry of coaxial precursor
            cartridge on fabricated lumen diameter in bioprinted tissue (concentration of alginate solution: 3.5%, n = 30). (C) Live/dead staining result for bioprinted
            tissue. Green: calcein-AM; red: ethidium homodimer-1; scale bar: 300 μm. (D) Immunostaining result for bioprinted tissue. Green: CD31; Blue: nucleus;
            scale bar: 300 μm. (E) Formation of endothelialized mid-scale vasculatures in bioprinted tissue via pre-set extrusion bioprinting technique. Red: alpha-
            smooth muscle actin; green: CD31; blue: nucleus; scale bar: 200 μm.

            Therefore, we aimed to generate a biochemical gradient in   applied to confirm the biochemical gradient environment
            the bioprinted tissue to induce endothelial cell sprouting   in the bioprinted tissue. Before the simulation, the effective
            and capillary formation.                           diffusion coefficient of VEGF through the dECM bioink
                                                               was derived experimentally (Figure 3A). The effective
               To generate a biochemical gradient in the bioprinted   diffusion coefficient of VEGF through the dECM bioink
            tissue, we modified the cell culture insert to create a diffusion   was 1.25 × 10  m /s, as derived from the data shown in
                                                                              2
                                                                          −11
            channel and bioprinted tissue in the cell culture insert. A   Figure 3B, which is within a reasonable range on the basis
            computational fluid dynamics simulation of diffusion was   of previous studies [17,18] . The effective diffusion coefficient

            Volume 9 Issue 4 (2023)                        169                         https://doi.org/10.18063/ijb.726
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