Chapter 14
Bioprinting of Complex Vascularized Tissues
Wei Zhu, Claire Yu, Bingjie Sun, and Shaochen Chen
Abstract
Functional vasculature is crucial for the maintenance of living tissues via the transport of oxygen, nutrients,
and metabolic waste products. As a result, insufficient vascularization in thick engineered tissues will lead to
cell death and necrosis due to mass transport and diffusional constraints. To circumvent these limitations,
we describe the development of a microscale continuous optical bioprinting (μCOB) platform for 3D
printing complex vascularized tissues with superior resolution and speed. By using the μCOB system,
endothelial cells and other supportive cells can be printed directly into hydrogels with precisely controlled
distribution and subsequent formation of lumen-like structures in vitro.
Key words 3D bioprinting, Vasculature, Complex microarchitecture, Hydrogels, Tissue engineering
1 Introduction
Tissue engineering is an emerging field of research that aims at
developing biological substitutes that can restore, maintain, or
improve tissue function or a whole organ [1, 2]. Ultimately, such
engineered tissue substitutes or organs can be used for in vivo
transplantation or in vitro drug screening. One of the key bottlenecks in tissue engineering is to provide sufficient vascularization
within thick engineered tissue constructs. Without proximity
(~150–200 μm) to the vascular network, cellular viability and tissue
function will be compromised within a very short time [3, 4]. The
incorporation of angiogenic growth factors is a typical strategy to
stimulate the host vasculature to infiltrate the engineered tissue
constructs after implantation [5–7]. However, this approach is
costly and not efficacious due to the relatively slow revascularization
process and short half-life of growth factors in vivo. A growing and
promising strategy is with the formation of prevascularized engineered tissue constructs in vitro prior to implantation. Currently,
this has shown great potential in providing sufficient vascularization
as well as improving cellular activity and tissue functions in vivo [8–
11]. PDMS molding techniques have also been used to fabricate
Alberto Rainer and Lorenzo Moroni (eds.), Computer-Aided Tissue Engineering: Methods and Protocols,
Methods in Molecular Biology, vol. 2147, https://doi.org/10.1007/978-1-0716-0611-7_14,
© Springer Science+Business Media, LLC, part of Springer Nature 2021
163
Bioprinting of Complex Vascularized Tissues
Wei Zhu, Claire Yu, Bingjie Sun, and Shaochen Chen
Abstract
Functional vasculature is crucial for the maintenance of living tissues via the transport of oxygen, nutrients,
and metabolic waste products. As a result, insufficient vascularization in thick engineered tissues will lead to
cell death and necrosis due to mass transport and diffusional constraints. To circumvent these limitations,
we describe the development of a microscale continuous optical bioprinting (μCOB) platform for 3D
printing complex vascularized tissues with superior resolution and speed. By using the μCOB system,
endothelial cells and other supportive cells can be printed directly into hydrogels with precisely controlled
distribution and subsequent formation of lumen-like structures in vitro.
Key words 3D bioprinting, Vasculature, Complex microarchitecture, Hydrogels, Tissue engineering
1 Introduction
Tissue engineering is an emerging field of research that aims at
developing biological substitutes that can restore, maintain, or
improve tissue function or a whole organ [1, 2]. Ultimately, such
engineered tissue substitutes or organs can be used for in vivo
transplantation or in vitro drug screening. One of the key bottlenecks in tissue engineering is to provide sufficient vascularization
within thick engineered tissue constructs. Without proximity
(~150–200 μm) to the vascular network, cellular viability and tissue
function will be compromised within a very short time [3, 4]. The
incorporation of angiogenic growth factors is a typical strategy to
stimulate the host vasculature to infiltrate the engineered tissue
constructs after implantation [5–7]. However, this approach is
costly and not efficacious due to the relatively slow revascularization
process and short half-life of growth factors in vivo. A growing and
promising strategy is with the formation of prevascularized engineered tissue constructs in vitro prior to implantation. Currently,
this has shown great potential in providing sufficient vascularization
as well as improving cellular activity and tissue functions in vivo [8–
11]. PDMS molding techniques have also been used to fabricate
Alberto Rainer and Lorenzo Moroni (eds.), Computer-Aided Tissue Engineering: Methods and Protocols,
Methods in Molecular Biology, vol. 2147, https://doi.org/10.1007/978-1-0716-0611-7_14,
© Springer Science+Business Media, LLC, part of Springer Nature 2021
163