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RESEARCH ARTICLE

In vitro pre-vascularization strategies for tissue

engineered constructs–Bioprinting and others

*
Andy Wen Loong Liew and Yilei Zhang
Singapore Centre for 3D Printing, School of Mechanical and Aerospace Engineering, Nanyang Technological Univer-
sity, Singapore 639798, Singapore

Abstract: Tissue-engineered products commercially available today have been limited to thin avascular tissue such as
skin and cartilage. The fabrication of thicker, more complex tissue still eludes scientists today. One reason for this is the
lack of effective techniques to incorporate functional vascular networks within thick tissue constructs. Vascular net-
works provide cells throughout the tissue with adequate oxygen and nutrients; cells located within thick un-vascularized
tissue implants eventually die due to oxygen and nutrient deficiency. Vascularization has been identified as one of the
key components in the field of tissue engineering. In order to fabricate biomimetic tissue which accurately recapitulates
our native tissue environment, in vitro pre-vascularization strategies need to be developed. In this review, we describe
various in vitro vascularization techniques developed recently which employ different technologies such as bioprinting,
microfluidics, micropatterning, wire molding, and cell sheet engineering. We describe the fabrication process and
unique characteristics of each technique, as well as provide our perspective on the future of the field.
Keywords: vascularization, vasculogenesis, endothelial, microfluidics, micropatterning, cell-sheet engineering, wire-
molding

*Correspondence to: Yilei Zhang, Singapore Centre for 3D Printing, School of Mechanical and Aerospace Engineering, Nanyang Techno-
logical University, Singapore 639798, Singapore: E-mail: ylzhang@ntu.edu.sg
Received: November 11, 2016; Accepted: December 14, 2016; Published Online: January 23, 2017
Citation: Liew A W L and Zhang Y, 2017, In vitro pre-vascularization strategies for tissue engineered constructs — Bioprinting and
others. International Journal of Bioprinting, vol.3(1): 3–17. http://dx.doi.org/10.18063/IJB.2017.01.008.

1. Introduction around. Research by the U.S. Department of Health
T alone, 22 people waiting for organ transplants die each
and Human Services found that in the United States
here is a wide spectrum of human pathologies
which plague mankind and affect our quality of
[1]
day due to shortage of donor organs . Moreover, the
life. These diseases often lead to organ failure
and even death of the patient. The conventional treat- percentage gap between the number of patients on the
waiting list and the number of organ donors has been
ment for organ failure would be an organ transplant, steadily increasing every year. Tissue engineering has
where the patient’s damaged organ is replaced by a shown promising signs to be a solution to this problem.
functional and compatible donor organ. Although or- The term tissue engineering was first coined in
gan transplantation has proven its efficacy over the 1993 by Langer and Vacanti in their highly influential
[2]
years, thousands of people continue to lose their lives paper . Tissue engineering is a cross-disciplinary
every year due to organ failure. The reason for this is field of research, comprising the principles of biology
the demand and supply disparity of donor organs. The and engineering to create functional tissue in a lab in
demand for donor organs far exceeds the supply, and order to replace or restore damaged tissue in a patient.
there are simply not enough donor organs to go A patient suffering from tissue injury, such as skin burn,

In vitro pre-vascularization strategies for tissue engineered constructs–Bioprinting and others. © 2017 Andy Wen Loong Liew. This is an Open Access
article distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International License (http://creativecommons.
org/licenses/by-nc/4.0/), permitting all non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
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