title: Vascularization of three-dimensional collagen hydrogels using ultrasound standing wave fields.
abstract: The successful fabrication of large, three-dimensional (3-D) tissues and organs in vitro requires the rapid development of a vascular network to maintain cell viability and tissue function. In this study, we utilized an application of ultrasound standing wave field (USWF) technology to vascularize 3-D, collagen-based hydrogels in vitro. Acoustic radiation forces associated with USWF were used to noninvasively organize human endothelial cells into distinct, multicellular planar bands within 3-D collagen gels. The formation and maturation of capillary-like endothelial cell sprouts were monitored over time and compared with sham-exposed collagen constructs, which were characterized by a homogeneous cell distribution. USWF-induced cell banding accelerated the formation and elongation of capillary-like sprouts, promoted collagen fiber alignment and resulted in the maturation of endothelial cell sprouts into lumen-containing, anastomosing networks found throughout the entire volume of the collagen gel. USWF-induced endothelial cell networks contained large, arteriole-sized lumen areas that branched into smaller, capillary-sized structures indicating the development of vascular tree-like networks. In contrast, sprout formation was delayed in sham-exposed collagen gels and endothelial cell networks were absent from sham gel centers and failed to develop into the vascular tree-like structures found in USWF-exposed constructs. Our results demonstrate that USWF technology leads to rapid and extensive vascularization of 3-D collagen-based engineered tissue and, therefore, provide a new strategy to vascularize engineered tissues in vitro.
authors.affiliation: Department of Biomedical Engineering, University of Rochester, Rochester, NY 14642, USA. denise_hocking@urmc.rochester.edu
authors.forename: Kelley A
authors.initials: KA
authors.lastname: Garvin
authors.forename: Diane
authors.initials: D
authors.lastname: Dalecki
authors.forename: Denise C
authors.initials: DC
authors.lastname: Hocking
mesh_terms: D001187:Artificial Organs; D002196:Capillaries / Q000166:cytology* / Q000254:growth & development*; D049109:Cell Proliferation; D002470:Cell Survival; D002478:Cells, Cultured; D003094:Collagen / Q000378:metabolism*; D042783:Endothelial Cells / Q000378:metabolism*; D006801:Humans; D020100:Hydrogels; D018919:Neovascularization, Physiologic; D023822:Tissue Engineering / Q000379:methods*; D014465:Ultrasonics
chemical_list: D020100:Hydrogels; D003094:Collagen