title: Perfusable branching microvessel bed for vascularization of engineered tissues.
abstract: Vascularization is critical for the survival of engineered tissues in vitro and in vivo. In vivo, angiogenesis involves endothelial cell proliferation and sprouting followed by connection of extended cellular processes and subsequent lumen propagation through vacuole fusion. We mimicked this process in engineering an organized capillary network anchored by an artery and a vein. The network was generated by inducing directed capillary sprouting from vascular explants on micropatterned substrates containing thymosin β4-hydrogel. The capillary outgrowths connected between the parent explants by day 21, a process that was accelerated to 14 d by application of soluble VEGF and hepatocyte growth factor. Confocal microscopy and transmission electron microscopy indicated the presence of tubules with lumens formed by endothelial cells expressing CD31, VE-cadherin, and von Willebrand factor. Cardiac tissues engineered around the resulting vasculature exhibited improved functional properties, cell striations, and cell-cell junctions compared with tissues without prevascularization. This approach uniquely allows easy removal of the vasculature from the microfabricated substrate and easy seeding of the tissue specific cell types in the parenchymal space.
authors.affiliation: Department of Chemical Engineering and Applied Chemistry, University of Toronto, Toronto, ON, Canada M5S 3G9.
authors.forename: Loraine L Y
authors.initials: LL
authors.lastname: Chiu
authors.forename: Miles
authors.initials: M
authors.lastname: Montgomery
authors.forename: Yan
authors.initials: Y
authors.lastname: Liang
authors.forename: Haijiao
authors.initials: H
authors.lastname: Liu
authors.forename: Milica
authors.initials: M
authors.lastname: Radisic
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D001807:Blood Vessel Prosthesis; D015820:Cadherins / Q000378:metabolism; D017228:Hepatocyte Growth Factor / Q000008:administration & dosage; D006801:Humans; D020100:Hydrogels; D051379:Mice; D008822:Mice, Transgenic; D018613:Microscopy, Confocal; D055806:Microvessels / Q000187:drug effects / Q000254:growth & development* / Q000502:physiology; D018919:Neovascularization, Physiologic; D010477:Perfusion; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013947:Thymosin; D023822:Tissue Engineering / Q000379:methods*; D054457:Tissue Scaffolds; D042461:Vascular Endothelial Growth Factor A / Q000008:administration & dosage; D014841:von Willebrand Factor / Q000378:metabolism; D000099201:Thymosin beta(4); D000099152:Cadherin 5
chemical_list: D015703:Antigens, CD; D015820:Cadherins; D017228:Hepatocyte Growth Factor; D020100:Hydrogels; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D013947:Thymosin; D042461:Vascular Endothelial Growth Factor A; D014841:von Willebrand Factor; D000099201:Thymosin beta(4); D000099152:Cadherin 5