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Author Notes:

nick.willett@emory.edu

M.A.R. and E.A.E. performed in vitro experiments and analyzed in vitro data. S.A.L. performed computational simulations and analysis with guidance from J.A.W. L.B.W. guided and performed multivariate gene expression data analysis with M.A.R. M.A.R., L.K., J.A.W., J.D.B., R.E.G., and N.J.W. designed the experiments. All authors edited and approved the final manuscript.

We wish to acknowledge the core facilities at the Parker H. Petit Institute for Bioengineering and Bioscience at the Georgia Institute of Technology for the use of their shared equipment, services, and expertise.

The authors declare that they have no competing interests.

Subject:

Research Funding:

This work was supported by funding from the NIH (grant R01 AR069297). This material is the result of work supported with resources and the use of facilities at the Atlanta VA Medical Center along with funding from the VA (grant 5 I01 RX001985); the contents do not represent the views of the U.S. Department of Veterans Affairs or the U.S. government.

Keywords:

  • Science & Technology
  • Multidisciplinary Sciences
  • Science & Technology - Other Topics
  • COLLAGEN GELS
  • GROWTH-FACTOR
  • PROLIFERATION
  • RECEPTOR
  • CELLS
  • MODEL
  • FLOW
  • YAP

Extracellular matrix compression temporally regulates microvascular angiogenesis

Tools:

Journal Title:

SCIENCE ADVANCES

Volume:

Volume 6, Number 34

Publisher:

Type of Work:

Article | Final Publisher PDF

Abstract:

Mechanical cues influence tissue regeneration, and although vasculature is known to be mechanically sensitive, little is known about the effects of bulk extracellular matrix deformation on the nascent vessel networks found in healing tissues. Previously, we found that dynamic matrix compression in vivo potently regulated revascularization during bone tissue regeneration; however, whether matrix deformations directly regulate angiogenesis remained unknown. Here, we demonstrated that load initiation time, magnitude, and mode all regulate microvascular growth, as well as upstream angiogenic and mechanotransduction signaling pathways. Immediate load initiation inhibited angiogenesis and expression of early sprout tip cell selection genes, while delayed loading enhanced microvascular network formation and upstream signaling pathways. This research provides foundational understanding of how extracellular matrix mechanics regulate angiogenesis and has critical implications for clinical translation of new regenerative medicine therapies and physical rehabilitation strategies designed to enhance revascularization during tissue regeneration.

Copyright information:

© 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works

This is an Open Access work distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International License (https://creativecommons.org/licenses/by-nc/4.0/).
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