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Issue 6, 2020
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Functional angiogenesis requires microenvironmental cues balancing endothelial cell migration and proliferation

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Abstract

Angiogenesis is a complex morphogenetic process that involves intimate interactions between multicellular endothelial structures and their extracellular milieu. In vitro models of angiogenesis can aid in reducing the complexity of the in vivo microenvironment and provide mechanistic insight into how soluble and physical extracellular matrix cues regulate this process. To investigate how microenvironmental cues regulate angiogenesis and the function of resulting microvasculature, we multiplexed an established angiogenesis-on-a-chip platform that affords higher throughput investigation of 3D endothelial cell sprouting emanating from a parent vessel through defined biochemical gradients and extracellular matrix. We found that two fundamental endothelial cell functions, migration and proliferation, dictate endothelial cell invasion as single cells vs. multicellular sprouts. Microenvironmental cues that elicit excessive migration speed incommensurate with proliferation resulted in microvasculature with poor barrier function and an inability to transport fluid across the microvascular bed. Restoring the balance between migration speed and proliferation rate rescued multicellular sprout invasion, providing a new framework for the design of pro-angiogenic biomaterials that guide functional microvasculature formation for regenerative therapies.

Graphical abstract: Functional angiogenesis requires microenvironmental cues balancing endothelial cell migration and proliferation

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Article information


Submitted
25 Nov 2019
Accepted
20 Feb 2020
First published
20 Feb 2020

Lab Chip, 2020,20, 1153-1166
Article type
Paper

Functional angiogenesis requires microenvironmental cues balancing endothelial cell migration and proliferation

W. Y. Wang, D. Lin, E. H. Jarman, W. J. Polacheck and B. M. Baker, Lab Chip, 2020, 20, 1153
DOI: 10.1039/C9LC01170F

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