Biomedical Polymers With Heparin-Binding End Groups
Principal Investigator: Robert S Ward
Abstract: Endpoint immobilization of heparin on the surface of polymeric biomaterials is a well-established method for improving thrombo-resistance. The most effective currently-available heparinization methods are costly, multi-step procedures that may degrade the mechanical properties of the base polymer. This makes them impractical for both low-cost devices like IV catheters and for prosthetic implants in which retention of physical-mechanical properties is vital for assuring safety and efficacy, e.g., circulatory support devices and vascular grafts. The proposed study will determine the feasibility of synthesizing tough, thermoplastic polyurethane biomaterials with built-in covalently bonded end groups with binding sites for heparin. A novel diamine-diamide-alcohol (PIME-SME) synthesis procedure will be optimized for high yield and low cost. Several samples of Bionate (r), a biostable polycarbonate-urethane, will then be synthesized using the mono-functional PIME-SME in a range of bulk concentrations. The use of this new surface modifying end group will avoid the reduction of mechanical properties associated with modifications to the polymer backbone previously used for binding heparin. Heparinization will be performed by simply soaking the device or component made from the subject polymer in dilute heparin solution. Highly surface specific Sum Frequency Generation Vibrational Spectroscopy will be used to assure maximum concentration of heparin binding groups at the surface of the polymer before exposure to heparin, and to measure the resulting surface heparin concentration following heparin binding. The activity of the adsorbed heparin will first be determined by a chromogenic anti-Xa heparin assay. A biological assay that measures the amount of antithrombin III (ATIII) that binds to the heparinized surface will also be used to determine if the adsorbed heparin maintains a conformation that binds ATIII. From the analytical characterization and the biological assays, the optimal bulk concentration of PIME-SME will be determined to provide maximum heparin binding on the surface of the modified polymers. During Phase II, scale up to manufacturing on our existing continuous reactor will be performed following extensive in vivo and in vitro testing. In Phase III The Polymer Technology Group will offer polyurethanes and device components with heparin binding capacity for sales or license, as part of its existing catalog of biomaterials.
Funding Period: 2004-08-01 - 2006-07-31
more information: NIH RePORT