title: Prevascularization of a fibrin-based tissue construct accelerates the formation of functional anastomosis with host vasculature.
abstract: One critical obstacle facing tissue engineering is the formation of functional vascular networks that can support tissue survival in vivo. We hypothesized that prevascularizing a tissue construct with networks of well-formed capillaries would accelerate functional anastomosis with the host upon implantation. Fibrin-based tissues were prevascularized with capillary networks by coculturing human umbilical vein endothelial cells (HUVECs) and fibroblasts in fibrin gels for 1 week. The prevascularized tissue and nonprevascularized controls were implanted subcutaneously onto the dorsal surface of immune-deficient mice and retrieved at days 3, 5, 7 and 14. HUVEC-lined vessels containing red blood cells were evident in the prevascularized tissue by day 5, significantly earlier than nonprevascularized tissues (14 days). Analysis of the HUVEC-lined vessels demonstrated that the number and area of perfused lumens in the prevascularized tissue were significantly larger compared to controls. In addition, collagen deposition and a larger number of proliferating cells were evident in the prevascularized tissue at day 14. Our results demonstrate that prevascularizing a fibrin-based tissue with well-formed capillaries accelerates anastomosis with the host vasculature, and promotes cellular activity consistent with tissue remodeling. Our prevascularization strategy may be useful to design large three-dimensional engineered tissues.
authors.affiliation: Department of Biomedical Engineering, University of California Irvine, Irvine, California 92697-2715, USA.
authors.forename: Xiaofang
authors.initials: X
authors.lastname: Chen
authors.forename: Anna S
authors.initials: AS
authors.lastname: Aledia
authors.forename: Cyrus M
authors.initials: CM
authors.lastname: Ghajar
authors.forename: Craig K
authors.initials: CK
authors.lastname: Griffith
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Putnam
authors.forename: Christopher C W
authors.initials: CC
authors.lastname: Hughes
authors.forename: Steven C
authors.initials: SC
authors.lastname: George
mesh_terms: D000818:Animals; D002196:Capillaries / Q000187:drug effects / Q000254:growth & development; D002452:Cell Count; D049109:Cell Proliferation / Q000187:drug effects; D003094:Collagen / Q000378:metabolism; D004129:Dimethylpolysiloxanes / Q000494:pharmacology; D042783:Endothelial Cells / Q000166:cytology / Q000187:drug effects; D005337:Fibrin / Q000378:metabolism*; D006801:Humans; D051379:Mice; D018919:Neovascularization, Physiologic / Q000187:drug effects; D010477:Perfusion; D019919:Prosthesis Implantation; D023822:Tissue Engineering; D014471:Umbilical Veins / Q000166:cytology / Q000187:drug effects
chemical_list: D004129:Dimethylpolysiloxanes; D005337:Fibrin; D003094:Collagen