Rapid and efficient in vivo angiogenesis directed by electro-assisted bioprinting of alginate/collagen microspheres with human umbilical vein endothelial cell coating layer

Rui Yao^1*, Ahmed Yousef F. Alkhawtan¹, Ruoyu Chen¹, Jie Luan², Mingen Xu^3*

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¹ Key Laboratory for Advanced Materials Processing Technology of Ministry of Education, Biomanufacturing and Rapid Forming Technology Key Laboratory of Beijing, Department of Mechanical Engineering, Tsinghua University, Beijing, 100084, People’s Republic of China

² Plastic Surgery Hospital, Peking Union Medical College, Beijing, 100144, People’s Republic of China

³ Key Laboratory of Medical Information and Three-dimensional Bioprinting of Zhejiang Province, Hangzhou Dianzi University, Hangzhou 310018, China

IJB 2019, 5(1), 194 https://doi.org/10.18063/ijb.v5i2.194

(This article belongs to the Special Issue Bioprinting in Asia)

© Invalid date by the Author(s). This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution 4.0 International License ( https://creativecommons.org/licenses/by/4.0/ )

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Abstract

Rapid reconstruction of functional microvasculature is the urgent challenge of regenerative medicine and ischemia therapy development. The purpose of this study was to provide an alternative solution for obtaining functional blood vessel networks in vivo, through assessing whether hydrogel-based microspheres coated by human umbilical vein endothelial cells (HUVECs) can direct rapid and efficient in vivo angiogenesis without the addition of exogenous growth factors or other supporting cells. Uniform alginate microspheres with adjustable diameter were biofabricated by electro-assisted bioprinting technology. Collagen fibrils were evenly coated on the surface of alginate microspheres through simple self-assembly procedure, and collagen concentration is optimized to achieve the highest HUVECs adhesion and proliferation. Immunofluorescence staining and gene analysis confirmed the formation of the prevascularized tubular structure and significantly enhanced endothelial gene expression. HUVECs-coated hydrogel microspheres with different diameters were subcutaneously injected in immunedeficient mice, which demonstrated rapid blood vessel regeneration and functional anastomosis with host blood vessels within 1 week. Besides, microsphere diameter demonstrated influence on blood vessel density with statistical differences but showed no obvious influence on the area occupied by blood vessels. This study provided a powerful tool for rapid and minimalinvasion angiogenesis of bioprinting constructs and a potential method for vascularized tissue regeneration and ischemia treatment with clinically relevant dimensions.

Keywords

Angiogenesis

Human umbilical vein endothelial cells

Microspheres

Minimal-invasive

Vascular tissue engineering

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International Journal of Bioprinting, Electronic ISSN: 2424-8002 Print ISSN: 2424-7723, Published by AccScience Publishing