title: Vasculogenic dynamics in 3D engineered tissue constructs.
abstract: Implantable 3D engineered vascular tissue constructs can be formed by co-culturing endothelial and fibroblast cells on macroporous scaffolds. Here we show that these constructs can be used for studying the dynamics of neovascular formation in-vitro by a combination of live confocal imaging and an array of image processing and analysis tools, revealing multiple distinct stages of morphogenesis. We show that this process involves both vasculogenic and angiogenic elements, including an initial endothelial multicellular cluster formation followed by rapid extensive sprouting, ultimately resulting in a stable interconnected endothelial network morphology. This vascular morphogenesis is time-correlated with the deposition and formation of an extensive extra-cellular matrix environment. We further show that endothelial network junctions are formed by two separate morphogenic mechanisms of anastomosis and cluster thinning.
authors.affiliation: Department of Biomedical Engineering, Technion - Israel Institute of Technology, Haifa, Israel.|Wyss Institute for Biologically Inspired Engineering, Harvard University, Cambridge, MA 02138, United States.
authors.forename: Yaron J
authors.initials: YJ
authors.lastname: Blinder
authors.affiliation: Department of Biomedical Engineering, Technion - Israel Institute of Technology, Haifa, Israel.
authors.forename: Alina
authors.initials: A
authors.lastname: Freiman
authors.affiliation: Department of Biomedical Engineering, Technion - Israel Institute of Technology, Haifa, Israel.
authors.forename: Noa
authors.initials: N
authors.lastname: Raindel
authors.affiliation: School of Engineering and Applied Sciences, Harvard University, Cambridge, MA 02138, United States.|Wyss Institute for Biologically Inspired Engineering, Harvard University, Cambridge, MA 02138, United States.
authors.forename: David J
authors.initials: DJ
authors.lastname: Mooney
authors.affiliation: Department of Biomedical Engineering, Technion - Israel Institute of Technology, Haifa, Israel.
authors.forename: Shulamit
authors.initials: S
authors.lastname: Levenberg
mesh_terms: D018929:Cell Culture Techniques; D042783:Endothelial Cells / Q000378:metabolism; D016326:Extracellular Matrix Proteins / Q000378:metabolism; D005347:Fibroblasts / Q000378:metabolism; D006801:Humans; D018919:Neovascularization, Physiologic; D023822:Tissue Engineering / Q000379:methods; D054457:Tissue Scaffolds; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000378:metabolism
chemical_list: D016326:Extracellular Matrix Proteins; D040301:Vascular Endothelial Growth Factor Receptor-2