Chapter 18
Methods to Generate Tube Micropatterns for Epithelial
Morphogenetic Analyses and Tissue Engineering
Minerva Bosch-Fortea and Fernando Martı ´n-Belmonte
Abstract
Cells live in a highly curved and folded 3D microenvironment within the human body. Since epithelial cells
in internal organs usually adopt a tubular shape, there is a need to engineer simple in vitro devices to
promote this cellular configuration. The aim of these devices would be to investigate epithelial morphogenesis and cell behavior—leading to the development of more sophisticated platforms for tissue engineering and regenerative medicine. In this chapter, we first explain the need for such epithelial tubular
micropatterns based on anatomical considerations and then survey methods that can be used to study
different aspects of epithelial tubulogenesis. The methods examined can broadly be divided into two classes:
conventional 2D microfabrication for the formation of simple epithelial tubes in substrates of different
stiffness; and 3D approaches to enable the self-assembly of organoid-derived epithelial tubes in a tubular
configuration. These methods demonstrate that modeling tubulogenesis in vitro with high resolution,
accuracy, and reproducibility is possible.
Key words 3D microenvironment, Epithelial morphogenesis, 2D microfabrication, Tissue
engineering
1 Introduction
Simple epithelial monolayers cover most internal surfaces of the
organism with epithelial cells being the fundamental building
blocks of many organs. Epithelial organs accomplish a plethora of
different functions: from digestion in the intestine to excretion
through the kidneys; from lactation in the mammary glands to
breathing through the lungs. Indeed, most of our internal organs
are made of polarized epithelial cells forming tubes, which organize
as an intricate network mostly in charge of transporting and distributing metabolites throughout the body [1]. The fine orchestration of the described morphogenetic processes is paramount for the
coordination and synchronization of the cells that would form
these tubular structures.
Kyra Campbell and Eric Theveneau (eds.), The Epithelial-to Mesenchymal Transition: Methods and Protocols,
Methods in Molecular Biology, vol. 2179, https://doi.org/10.1007/978-1-0716-0779-4_18,
© Springer Science+Business Media, LLC, part of Springer Nature 2021
227
Methods to Generate Tube Micropatterns for Epithelial
Morphogenetic Analyses and Tissue Engineering
Minerva Bosch-Fortea and Fernando Martı ´n-Belmonte
Abstract
Cells live in a highly curved and folded 3D microenvironment within the human body. Since epithelial cells
in internal organs usually adopt a tubular shape, there is a need to engineer simple in vitro devices to
promote this cellular configuration. The aim of these devices would be to investigate epithelial morphogenesis and cell behavior—leading to the development of more sophisticated platforms for tissue engineering and regenerative medicine. In this chapter, we first explain the need for such epithelial tubular
micropatterns based on anatomical considerations and then survey methods that can be used to study
different aspects of epithelial tubulogenesis. The methods examined can broadly be divided into two classes:
conventional 2D microfabrication for the formation of simple epithelial tubes in substrates of different
stiffness; and 3D approaches to enable the self-assembly of organoid-derived epithelial tubes in a tubular
configuration. These methods demonstrate that modeling tubulogenesis in vitro with high resolution,
accuracy, and reproducibility is possible.
Key words 3D microenvironment, Epithelial morphogenesis, 2D microfabrication, Tissue
engineering
1 Introduction
Simple epithelial monolayers cover most internal surfaces of the
organism with epithelial cells being the fundamental building
blocks of many organs. Epithelial organs accomplish a plethora of
different functions: from digestion in the intestine to excretion
through the kidneys; from lactation in the mammary glands to
breathing through the lungs. Indeed, most of our internal organs
are made of polarized epithelial cells forming tubes, which organize
as an intricate network mostly in charge of transporting and distributing metabolites throughout the body [1]. The fine orchestration of the described morphogenetic processes is paramount for the
coordination and synchronization of the cells that would form
these tubular structures.
Kyra Campbell and Eric Theveneau (eds.), The Epithelial-to Mesenchymal Transition: Methods and Protocols,
Methods in Molecular Biology, vol. 2179, https://doi.org/10.1007/978-1-0716-0779-4_18,
© Springer Science+Business Media, LLC, part of Springer Nature 2021
227