title: A biologically active VEGF construct in vitro: implications for bioengineering-improved prosthetic vascular grafts.
abstract: Prosthetic arterial grafts are unable to develop an intact endothelial lining after implantation, predisposing them to fail. Strategies have been sought to enhance endothelialization using growth factors and cytokines. This study assessed the biologic activity of vascular endothelial growth factor (VEGF) covalently linked to bovine serum albumin (BSA). Native and modified VEGF were assayed for endothelial cell migration and proliferation. Migration assays were performed comparing the effects of 2% fetal bovine serum (FBS), 50 ng/mL, 100 ng/mL, and 200 ng/mL of native VEGF and VEGF-BSA. Proliferation assays were performed by using Alamar Blue comparing cellular growth in 1% FBS, 10% FBS, 100 ng/mL unbound VEGF, and 100 ng/mL VEGF-BSA. VEGF is a potent chemotactic agent for endothelial cells in both unbound and bound states. Native VEGF solutions (50 ng/mL, 100 ng/mL, and 200 ng/mL) stimulated 23.9 cells/high power field (HPF), 35.3 cells/HPF, and 49.1 cells/HPF (p < 0.005). VEGF-BSA solutions stimulated 25.9 cells/HPF, 39.1 cells/HPF, and 69.0 cells/HPF (p < 0.001). VEGF-BSA and native VEGF supported similar increased cellular proliferation compared with 1% FBS media (p < 0.002). Modified VEGF retains its chemotactic and proliferative properties in vitro. These findings suggest that bare prosthetic surfaces lined with VEGF bound to a "basecoat" albumin may support endothelial cell proliferation and migration and thereby offer new strategies to improve graft patency.
authors.affiliation: Department of Surgery, Division of Vascular Surgery, Beth Israel Deaconess Medical Center, Vascular Surgery Research Laboratory, Harvard Institute of Medicine Building, 4 Blackfan Circle, Room 130, Boston, Massachusetts 02115, USA. docstone@usa.net
authors.forename: David
authors.initials: D
authors.lastname: Stone
authors.forename: Matthew
authors.initials: M
authors.lastname: Phaneuf
authors.forename: Nayan
authors.initials: N
authors.lastname: Sivamurthy
authors.forename: Frank W
authors.initials: FW
authors.lastname: LoGerfo
authors.forename: William C
authors.initials: WC
authors.lastname: Quist
mesh_terms: D001807:Blood Vessel Prosthesis; D002455:Cell Division / Q000502:physiology; D002465:Cell Movement / Q000502:physiology; D002478:Cells, Cultured; D016228:Endothelial Growth Factors / Q000737:chemistry / Q000502:physiology*; D006801:Humans; D008222:Lymphokines / Q000737:chemistry / Q000502:physiology*; D012710:Serum Albumin, Bovine / Q000737:chemistry; D023822:Tissue Engineering; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
chemical_list: D016228:Endothelial Growth Factors; D008222:Lymphokines; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D012710:Serum Albumin, Bovine