Extracellular matrix compression temporally regulates microvascular angiogenesis

• Type of Material: Article
• Authors: M.A. Ruehle, Georgia Institute of Technology; E.A. Eastburn, Georgia Institute of Technology; S.A. LaBelle, University of Utah; L. Krishnan, Georgia Institute of Technology; J.A. Weiss, University of Utah; J.D. Boerckel, University of Pennsylvania; L.B. Wood, Georgia Institute of Technology; Robert Guldberg, Emory University; Nick Willett, Emory University
• Language: English
• Date: 2020-08-01
• Publisher: AMER ASSOC ADVANCEMENT SCIENCE
• Publication Version: Final Published Version
• Copyright Statement: © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works
• License: Creative Commons Attribution-NonCommercial 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1126/sciadv.abb6351
• Title of Journal or Parent Work: SCIENCE ADVANCES
• Volume: 6
• Issue: 34
• Grant/Funding Information: 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 - Other Topics; Science & Technology; Multidisciplinary Sciences; FLOW; YAP; COLLAGEN GELS; GROWTH-FACTOR; CELLS; MODEL; RECEPTOR; PROLIFERATION
• Research Categories: Biology, Cell

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.