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RESEARCH ARTICLE

Angiogenesis in Free-Standing Two-Vasculature-Embedded

Scaffold Extruded by Two-Core Laminar Flow Device

Chanh Trung Nguyen , Van Thuy Duong , Chang Ho Hwang , Kyo-in Koo *
2
1
1
1
1 Major of Biomedical Engineering, Department of Electrical, Electronic and Computer Engineering, University of Ulsan,
Ulsan, Republic of Korea
2 Department of Physical and Rehabilitation Medicine, Chungnam National University Sejong Hospital, College of
Medicine, Chungnam National University, Sejong, Republic of Korea

Abstract: Rapid construction of pre-vascular structure is highly desired for engineered thick tissue. However, angiogenesis in
free-standing scaffold has been rarely reported because of limitation in growth factor (GF) supply into the scaffold. This study,
for the 1 time, investigated angiogenic sprouting in free-standing two-vasculature-embedded scaffold with three different
st
culture conditions and additional GFs. A two-core laminar flow device continuously extruded one vascular channel with
human umbilical vein endothelial cells (HUVECs) and a 3 mg/ml type-1 collagen, one hollow channel, and a shell layer with
2% w/v gelatin-alginate (70:30) composite. Under the GF flowing condition, angiogenic sprouting from the HUVEC vessel
had started since day 1 and gradually grew toward the hollow channel on day 10. Due to the medium flowing, the HUVECs
showed elongated spindle-like morphology homogeneously. Their viability has been over 80% up to day 10. This approach
could apply to vascular investigation, and drug discovery further, not only to the engineered thick tissue.
Keywords: Angiogenesis; Pre-vascularized tissue; Two-core vasculature; Gelatin-alginate; Free standing; Culture condition

*Correspondence to: Kyo-in Koo, Major of Biomedical Engineering, Department of Electrical, Electronic and Computer Engineering,
University of Ulsan, Nam-gu, Ulsan 44610, Republic of Korea; kikoo@ulsan.ac.kr
Received: January 19, 2022; Accepted: April 1, 2022; Published Online: May 13, 2022

Citation: Nguyen CT, Duong VT, Hwang CH, et al., 2022, Angiogenesis in Free-Standing Two-Vasculature-Embedded
Scaffold Extruded by Two-Core Laminar Flow Device. Int J Bioprint, 8(3):557. http://doi.org/10.18063/ijb.v8i3.557

1. Introduction their achievement but still require more development
because prolonged fabrication time and complex manual
The vascular network densely permeates organs to processes can damage cell viability. In addition, limited
provide efficient mass transfer in body . These branched vasculature layer number and complex fabrication
[1]
vessels transfer nutrients and oxygen and withdraw process of mesovasculatures are other challenges that
metabolic waste from organs . The functioning vascular need to be tackled .
[2]
[14]
network is essential as well when creating engineered Therefore, not only the pre-vascularizing method
thick tissue. In in vivo environment, cells are generally but also a method for easy angiogenesis is required for
located within less than 200 µm from blood vessels to the engineered thick tissue. Some angiogenesis process
avoid ischemic conditions . However, fabricated tissue inside a microfluidic chip has been investigated [15-17] .
[3]
in vitro lacked the vasculature network so that cells inside However, angiogenesis in free-standing scaffolds has
the engineered tissue often received nutrients by diffusion been rarely reported because supplying growth factor
over 200 µm, at the worst case over 1 mm . (GF) or implementing GF gradient inside the 3D
[4]
To fabricate pre-vasculature channels, various scaffolds is not easy. Couple of reports demonstrated
methods including electrospinning , molding , laser angiogenesis with a single-channel structure. Duong et al.
[5]
[6]
degradation , co-axial extruding [8-10] , acoustofluidic extruded the double-layered single-vascular scaffold with
[7]
extruding , cell sheet stacking , and cell coculture human umbilical vein endothelial cell (HUVEC) and
[13]
[11]
[12]
have been proposed. These approaches have demonstrated human aortic smooth muscle cell (HASMC) . In their
[18]
© 2022 Author(s). This is an Open Access article distributed under the terms of the Creative Commons Attribution License, permitting distribution and
reproduction in any medium, provided the original work is properly cited.
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