title: Stretch-induced intussuceptive and sprouting angiogenesis in the chick chorioallantoic membrane.
abstract: Vascular systems grow and remodel in response to not only metabolic needs, but also mechanical influences as well. Here, we investigated the influence of tissue-level mechanical forces on the patterning and structure of the chick chorioallantoic membrane (CAM) microcirculation. A dipole stretch field was applied to the CAM using custom computer-controlled servomotors. The topography of the stretch field was mapped using finite element models. After 3days of stretch, Sholl analysis of the CAM demonstrated a 7-fold increase in conducting vessel intersections within the stretch field (p<0.01). The morphometric analysis of intravital microscopy and scanning electron microscopy (SEM) images demonstrated that the increase vessel density was a result of an increase in interbranch distance (p<0.01) and a decrease in bifurcation angles (p<0.01); there was no significant increase in conducting vessel number (p>0.05). In contrast, corrosion casting and SEM of the stretch field capillary meshwork demonstrated intense sprouting and intussusceptive angiogenesis. Both planar surface area (p<0.05) and pillar density (p<0.01) were significantly increased relative to control regions of the CAM. We conclude that a uniaxial stretch field stimulates the axial growth and realignment of conducting vessels as well as intussusceptive and sprouting angiogenesis within the gas exchange capillaries of the ex ovo CAM.
authors.affiliation: Laboratory of Adaptive and Regenerative Biology, Brigham & Women's Hospital, Harvard Medical School, Boston, MA, USA.
authors.forename: Janeil
authors.initials: J
authors.lastname: Belle
authors.affiliation: Laboratory of Adaptive and Regenerative Biology, Brigham & Women's Hospital, Harvard Medical School, Boston, MA, USA.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Ysasi
authors.affiliation: Laboratory of Adaptive and Regenerative Biology, Brigham & Women's Hospital, Harvard Medical School, Boston, MA, USA.
authors.forename: Robert D
authors.initials: RD
authors.lastname: Bennett
authors.affiliation: Faculty of Mechanical Engineering, University of Kragujevac, Serbia.
authors.forename: Nenad
authors.initials: N
authors.lastname: Filipovic
authors.affiliation: Mechanical Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA.
authors.forename: Mohammad Imani
authors.initials: MI
authors.lastname: Nejad
authors.affiliation: Mechanical Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA.
authors.forename: David L
authors.initials: DL
authors.lastname: Trumper
authors.affiliation: Institute of Functional and Clinical Anatomy, University Medical Center of Johannes Gutenberg-University, Mainz, Germany.
authors.forename: Maximilian
authors.initials: M
authors.lastname: Ackermann
authors.affiliation: Institute of Functional and Clinical Anatomy, University Medical Center of Johannes Gutenberg-University, Mainz, Germany.
authors.forename: Willi
authors.initials: W
authors.lastname: Wagner
authors.affiliation: Molecular and Integrative Physiological Sciences, Harvard School of Public Health, Boston, MA, USA.
authors.forename: Akira
authors.initials: A
authors.lastname: Tsuda
authors.affiliation: Institute of Functional and Clinical Anatomy, University Medical Center of Johannes Gutenberg-University, Mainz, Germany.
authors.forename: Moritz A
authors.initials: MA
authors.lastname: Konerding
authors.affiliation: Laboratory of Adaptive and Regenerative Biology, Brigham & Women's Hospital, Harvard Medical School, Boston, MA, USA. Electronic address: smentzer@partners.org.
authors.forename: Steven J
authors.initials: SJ
authors.lastname: Mentzer
mesh_terms: D000818:Animals; D002196:Capillaries / Q000502:physiology* / Q000648:ultrastructure; D002642:Chick Embryo; D049033:Chorioallantoic Membrane / Q000098:blood supply*; D016319:Corrosion Casting; D020342:Finite Element Analysis; D040542:Mechanotransduction, Cellular; D008833:Microcirculation; D064347:Microscopy, Electrochemical, Scanning; D008856:Microscopy, Fluorescence; D018715:Microscopy, Video; D008955:Models, Cardiovascular; D018919:Neovascularization, Physiologic; D013314:Stress, Mechanical; D013997:Time Factors
keywords: Chorioallantoic membrane; Fluorescence microscopy; Microcirculation; Micromechanics; Scanning electron microscopy; Sprouting and intussusceptive angiogenesis; Stretch