37
© Springer Nature Switzerland AG 2018
S. Gerecht (ed.), Biophysical Regulation of Vascular Differentiation and
Assembly, Biological and Medical Physics, Biomedical Engineering,
https://doi.org/10.1007/978-3-319-99319-5_2
Chapter 2
Mechanical Regulation of Vascularization
in Three-Dimensional Engineered Tissues
Barak Zohar, Shira Landau, and Shulamit Levenberg
2.1 Introduction
Three-dimensional (3D) tissue engineering generally involves the design of 3D
polymeric scaffolds in combination with one or more cell types, to form implantable, tissue-like devices. Such engineered tissues can be used to replace autologous
tissue conventionally used to repair substantial tissue damage and can serve as
tissue- scale models to study normal and diseased biological processes (e.g., drug
screening tests). Vascularization of engineered tissue constructs is a challenge of
great significance in the field of regenerative medicine. Without a stable and perfusable blood vessel network providing oxygen and nutrients, cells cannot survive tissue dimension growth beyond several hundreds of microns, due to diffusion
limitations. Several approaches have been applied to promote the vascularization of
engineered implants, including pre-vascularization of implants relying on selfassembly of endothelial cells and mural cells to vessels. The mechanisms by which
endothelial cells (ECs) self-assemble into vascular networks are quite diverse.
Current scientific understanding generally separates these processes into vasculogenesis and angiogenesis, where vasculogenesis refers to the de novo creation of
vascular networks from endothelial progenitor cells (angioblasts), as seen in the
embryo’s primitive vascular plexus. Angiogenesis refers to the expansion of existing vascular networks into new blood vessels, via mechanisms such as sprouting,
intussusception (vessel splitting), and vessel fusion. During angiogenesis, ECs exert
mechanical forces on their environment while invading, proliferating and migrating.
These forces are generated by the contraction of several cytoskeletal proteins such
as actin, microtubules, and actomyosin and are affected by environmental cues.
Additionally, EC lining blood vessel walls are continuously exposed to mechanical
B. Zohar · S. Landau · S. Levenberg (*)
Department of Biomedical Engineering, Technion-Israel Institute of Technology, Haifa, Israel
e-mail: shulamit@bm.technion.ac.il
© Springer Nature Switzerland AG 2018
S. Gerecht (ed.), Biophysical Regulation of Vascular Differentiation and
Assembly, Biological and Medical Physics, Biomedical Engineering,
https://doi.org/10.1007/978-3-319-99319-5_2
Chapter 2
Mechanical Regulation of Vascularization
in Three-Dimensional Engineered Tissues
Barak Zohar, Shira Landau, and Shulamit Levenberg
2.1 Introduction
Three-dimensional (3D) tissue engineering generally involves the design of 3D
polymeric scaffolds in combination with one or more cell types, to form implantable, tissue-like devices. Such engineered tissues can be used to replace autologous
tissue conventionally used to repair substantial tissue damage and can serve as
tissue- scale models to study normal and diseased biological processes (e.g., drug
screening tests). Vascularization of engineered tissue constructs is a challenge of
great significance in the field of regenerative medicine. Without a stable and perfusable blood vessel network providing oxygen and nutrients, cells cannot survive tissue dimension growth beyond several hundreds of microns, due to diffusion
limitations. Several approaches have been applied to promote the vascularization of
engineered implants, including pre-vascularization of implants relying on selfassembly of endothelial cells and mural cells to vessels. The mechanisms by which
endothelial cells (ECs) self-assemble into vascular networks are quite diverse.
Current scientific understanding generally separates these processes into vasculogenesis and angiogenesis, where vasculogenesis refers to the de novo creation of
vascular networks from endothelial progenitor cells (angioblasts), as seen in the
embryo’s primitive vascular plexus. Angiogenesis refers to the expansion of existing vascular networks into new blood vessels, via mechanisms such as sprouting,
intussusception (vessel splitting), and vessel fusion. During angiogenesis, ECs exert
mechanical forces on their environment while invading, proliferating and migrating.
These forces are generated by the contraction of several cytoskeletal proteins such
as actin, microtubules, and actomyosin and are affected by environmental cues.
Additionally, EC lining blood vessel walls are continuously exposed to mechanical
B. Zohar · S. Landau · S. Levenberg (*)
Department of Biomedical Engineering, Technion-Israel Institute of Technology, Haifa, Israel
e-mail: shulamit@bm.technion.ac.il