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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
diameter of hundreds of micrometers, formed by the pre-set modified porcine-to-human cardiac xenotransplantation. N
extrusion bioprinting technique, and capillary branches, with Engl J Med, 387(1):35–44.
a diameter of tens of micrometers, formed by endothelial https://doi.org/10.1056/NEJMoa2201422
sprouting, were able to effectively deliver materials, 3. Cohen BP, Bernstein JL, Morrison KA, et al., 2018, Tissue
such as oxygen and nutrients to cells. In conclusion, the engineering the human auricle by auricular chondrocyte-
strategy for multi-scale vascularization in bioprinted tissue mesenchymal stem cell co-implantation. PLoS One,
demonstrated in this work is expected to become a useful 13(10):e0202356.
technology for bioartificial tissue or organ development.
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.
Nat Med, 16(7):814–820.
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

