Research Project
6134229
Medium (6-8mm) and small (<5mm) internal diameter prosthetic grafts continue to have clinically unacceptable high failure rates. Dacron vascular grafts have had limited use due to sealing of the porous graft matrix with proteins that have numerous adverse effects. Our objective is to create a sealed Dacron vascular graft using a polyether-based urethane with carboxylic acid groups (PEU-COOH) to which antithrombin (recombinant hirudin (rHir)) and mitogenic (vascular endothelial growth factor (VEGF)) agents will be covalently bound. Our hypothesis is Dacron grafts sealed with PEU-COOH (PEU-D) will create sites to link biologic agents to the graft surface, thereby emulating some of the natural healing properties. The specific aims are to: optimize PEU-COOH application conditions, characterize PEU-D physical and chemical properties, maximize basecoat binding, covalently bind rHir and VEGF to the PEU-D surface, determine surface bound antithrombin and mitogenic properties and assess biostability of the immobilized proteins under flow conditions. 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. Potentially, application of this technology to small- diameter vascular grafts could have an annual market of over $700 million. PROPOSED COMMERCIAL APPLICATIONS: Development of a polyurethane sealant with protein binding properties would have a significant role in medical devices such as vascular grafts, catheters, artificial organs and wound dressings. Potentially, application of this technology to small-diameter vascular grafts could have an annual market of over $700 million.
