Gradient Hydrogels
Gradient hydrogels represent a pivotal and expanding direction of three-dimensional cell culture. Since various types of gradients play an important role in physiological and pathological processes in vivo, recreation of these gradients in vitro allows a
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Gradient Hydrogels Antonina Lavrentieva
Contents 1 Gradients In Vivo as Driving Force of Biological Processes 2 Tunable Hydrogels as Building Blocks for the Creation of In Vitro Gradients 2.1 Types of Gradients 2.2 Methods and Equipment for Gradient Hydrogels Production 2.3 Choice of Material 2.4 Gradient Characterization Approaches 3 Mechanical Gradients in Hydrogels and Their Influence on the Cells 3.1 Stiffness Gradients 3.2 Pore Architecture Gradients 3.3 Topographical Gradients 4 Biological/Biochemical Gradients in Hydrogels 5 Material Composition Gradients 6 Oxygen Gradients in Hydrogels 7 Hydrogels with Combined Multiple Gradients 8 Concluding Remarks and Future Perspectives References
Abstract Gradient hydrogels represent a pivotal and expanding direction of threedimensional cell culture. Since various types of gradients play an important role in physiological and pathological processes in vivo, recreation of these gradients in vitro allows a better understanding of cellular behavior, intercellular and cell– matrix interactions. Moreover, gradient hydrogels can advance the creation of functionally improved and physiologically relevant tissue engineered constructs. Another application of gradient hydrogels is the optimization of the 3D in vitro microenvironment (e.g., in terms of hydrogel stiffness or concentration of adhesion ligands). Tunable hydrogels provide researchers with a versatile toolbox to manufacture such gradients in vitro. In this chapter different types of in vivo and in vitro A. Lavrentieva (*) Gottfried Wilhelm Leibniz Universität Hannover, Institute of Technical Chemistry, Hannover, Germany e-mail: [email protected]
A. Lavrentieva
gradients in hydrogels will be presented. Equipment and methods for various gradient fabrications will be discussed. Furthermore, methods of gradient characterizations in hydrogels will be reported. As one of the most recent developments, the influence of low oxygen concentration on cells, as well as the creation and characterization of oxygen gradients in hydrogels will be described. In the last part, achievements in the creation of multiple combinatorial gradients will be presented. The aim of this chapter is to give the reader an overview on existing techniques and biological importance of gradient hydrogels in basic science as well as in applied research. Graphical Abstract
Keywords Gradient hydrogel fabrication, Gradient hydrogels, Hydrogel characterization, In vitro gradient systems, In vivo gradients, Oxygen gradients, Stiffness gradients
1 Gradients In Vivo as Driving Force of Biological Processes The growing complexity and specific spatial organization of multicellular organisms leads to the appearance of various gradients in tissues and organs. Already in 1901, Thomas Hunt Morgan observed different regeneration patterns in the body of crabs [1]. The polarity of organisms was also demonstrated in regeneration experiments on
Gradient Hydrogels
flatworms (if a worm was cut in half, each piece regenerated the missing part of the body). S
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