DEVELOPMENT OF A BIOLOGICALLY-ACTIVE VASCULAR GRAFT

Medium (6-8mm) and small (<5mm) internal diameter prosthetic grafts continue to have clinically unacceptable high failure rates. In phase I, an ionic polyurethane-sealed Dacron vascular graft (PEU-D) with reduced water permeation, excellent physical properties and co-valently bound anti-thrombin (recombinant hirudin of rHir) and mitogenic (vascular endothelial growth factor or VEGF) agents was developed. These surface bound agents were determined to be biologically active. Our objective in this proposal is to assess blood permeation and graft patency/healing of the PEU-D graft using a canine arterial grafting model. Our hypothesis is that implantation of this novel graft will prevent blood permeation thereby obviating the need for pre-clotting and improve graft patency and healing by emulating some of the natural properties of native vessels. The specific aims are to: 1) develop a batch synthesis for ionic polyurethane, 2) scale-up the process for sealing Dacron grafts, 3) evaluate PEU-D physical and chemical properties, 4) covalently link rHir and VEGF to PEU-D surface, 5) assess in vivo acute and chronic implantation periods and 6) examine macroscopically explanted grafts. Development of a polyurethane sealant with protein binding properties would have a significant role for medical devices such as vascular grafts catheters and artificial organs.