A biologically active VEGF construct in vitro: Implications for bioengineering-improved prosthetic vascular grafts

Prosthetic arterial grafts are unable to develop an intact endothelial lini ng after implantation, predisposing them to fail. Strategies have been soug ht to enhance endothelialization using growth factors and cytokines. This s tudy 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. Migrati on assays were performed comparing the effects of 2% fetal bovine serum (FB S), 50 ng/mL, 100 ng/mL, and 200 ng/mL of native VEGF and VEGF-BSA. Prolife ration 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 i s a potent chemotactic agent for endothelial cells in both unbound and boun d states. Native VEGF solutions (50 ng/mL, 100 ng/mL, and 200 ng/mL) stimul ated 23.9 cells/high power field (HPF), 35.3 cells/HPF, and 49.1 cells/HPF (12 < 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). M odified 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 mig ration and thereby offer new strategies to improve graft patency. (C) 2001 John Wiley & Sons, Inc.