title: Morphogenesis of 3D vascular networks is regulated by tensile forces.
abstract: Understanding the forces controlling vascular network properties and morphology can enhance in vitro tissue vascularization and graft integration prospects. This work assessed the effect of uniaxial cell-induced and externally applied tensile forces on the morphology of vascular networks formed within fibroblast and endothelial cell-embedded 3D polymeric constructs. Force intensity correlated with network quality, as verified by inhibition of force and of angiogenesis-related regulators. Tensile forces during vessel formation resulted in parallel vessel orientation under static stretching and diagonal orientation under cyclic stretching, supported by angiogenic factors secreted in response to each stretch protocol. Implantation of scaffolds bearing network orientations matching those of host abdominal muscle tissue improved graft integration and the mechanical properties of the implantation site, a critical factor in repair of defects in this area. This study demonstrates the regulatory role of forces in angiogenesis and their capacities in vessel structure manipulation, which can be exploited to improve scaffolds for tissue repair.
authors.affiliation: Department of Biomedical Engineering, Technion-Israel Institute of Technology, Haifa, 32000, Israel;
authors.forename: Dekel
authors.initials: D
authors.lastname: Rosenfeld
authors.affiliation: Department of Biomedical Engineering, Technion-Israel Institute of Technology, Haifa, 32000, Israel;
authors.forename: Shira
authors.initials: S
authors.lastname: Landau
authors.affiliation: Department of Biomedical Engineering, Technion-Israel Institute of Technology, Haifa, 32000, Israel;
authors.forename: Yulia
authors.initials: Y
authors.lastname: Shandalov
authors.affiliation: Department of Biomedical Engineering, Technion-Israel Institute of Technology, Haifa, 32000, Israel;
authors.forename: Noa
authors.initials: N
authors.lastname: Raindel
authors.affiliation: Department of Biomedical Engineering, Technion-Israel Institute of Technology, Haifa, 32000, Israel; Interdepartmental Program in Biotechnology, Technion-Israel Institute of Technology, Haifa, 32000, Israel;
authors.forename: Alina
authors.initials: A
authors.lastname: Freiman
authors.affiliation: Department of Biomedical Engineering, Technion-Israel Institute of Technology, Haifa, 32000, Israel;
authors.forename: Erez
authors.initials: E
authors.lastname: Shor
authors.affiliation: Department of Biomedical Engineering, Technion-Israel Institute of Technology, Haifa, 32000, Israel;
authors.forename: Yaron
authors.initials: Y
authors.lastname: Blinder
authors.affiliation: Department of Pathology and Laboratory Medicine, Brown University, Providence, RI 02906;
authors.forename: Herman H
authors.initials: HH
authors.lastname: Vandenburgh
authors.affiliation: School of Engineering and Applied Sciences, Harvard University, Cambridge, MA 02138; Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA 02115.
authors.forename: David J
authors.initials: DJ
authors.lastname: Mooney
authors.affiliation: Department of Biomedical Engineering, Technion-Israel Institute of Technology, Haifa, 32000, Israel; shulamit@bm.technion.ac.il.
authors.forename: Shulamit
authors.initials: S
authors.lastname: Levenberg
mesh_terms: D001808:Blood Vessels / Q000502:physiology*; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D009024:Morphogenesis; D018919:Neovascularization, Physiologic; D013718:Tensile Strength; D054457:Tissue Scaffolds
keywords: endothelial cells; engineered tissue; mechanical forces; vascularization