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Hypoxia and Matrix Manipulation for Vascular Engineering

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Biophysical Regulation of Vascular Differentiation and Assembly

Abstract

The great majority of cell types are known to be capable of sensing changes in O2 tension and in the extracellular matrix (ECM), resulting in various responses depending on the cell type and other factors in the microenvironment, such as cell–cell interactions. A growing body of evidence suggests that hypoxia greatly influences the processes of angiogenesis/vasculogenesis through the transcription of several genes, including vascular endothelial growth factor (VEGF), the major regulatory protein of angiogenesis/vasculogenesis. At the same time, the spatial and temporal distribution of ECM components affects ECM properties and growth factor (GF) availability, which, in turn, regulates vascular development. This chapter will discuss how hypoxia and the ECM influence vascular morphogenesis. It seeks a better understanding of vascular development by considering recent research and emerging technologies focused on controlling O2 tension and manipulating ECM properties. The first part of the chapter focuses on the influences of O2 tension and ECM distribution on vascular formation. The second part presents strategies for manipulating the microenvironment using synthetic biomaterials. Control over O2 in three-dimensional (3D) microenvironments is thoroughly highlighted, along with the currently available O2 measurement techniques and mathematical models that are necessary to monitor O2 gradients in 3D microenvironments. Finally, the chapter discusses the state-of-the-art technology in microfluidics and smart biomaterials to provide insight into its future direction.

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Acknowledgments

We would like to acknowledge funding from the AHA-Scientist Development grant, March of Dimes Basil O’Conner Starter Scholar award (both to S.G), and the National Institute of Health grant U54CA143868.

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Abaci, H.E., Hanjaya-Putra, D., Gerecht, S. (2011). Hypoxia and Matrix Manipulation for Vascular Engineering. In: Gerecht, S. (eds) Biophysical Regulation of Vascular Differentiation and Assembly. Biological and Medical Physics, Biomedical Engineering. Springer, New York, NY. https://doi.org/10.1007/978-1-4419-7835-6_7

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