MULTIFUNCTIONAL ANTITHROMBOGENIC SURFACES

THE LONG-TERM OBJECTIVES OF THIS PROJECT ARE THE METHODOLOGY DEVELOPMENT AND MANUFACTURING OF ANTITHROMBOGENIC SURFACES CONTAINING POLYETHYLENE OXIDE (PEO)-TETHERED BIOACTIVE COMPOUNDS THAT COUNTERACT OR INHIBIT THE MAJOR THROMBOGENIC EFFECTS KNOWN TO OCCUR WHEN A SURFACE IS EXPOSED TO BLOOD. THE SPECIFIC AIMS OF PHASE I ARE TO: (1) PRODUCE AND CHARACTERIZE IN DETAIL HEPARIN-ONLY AND UROKINASE-ONLY SURFACES IN TERMS OF TOTAL BIOACTIVES AND SURFACE BIOACTIVITY; AND (2) DEVELOP METHODOLOGY TO PRODUCE HEPARIN-UROKINASE SURFACES, WHICH WOULD BE EVALUATED FOR BIOACTIVITY AND ANTITHROMBOGENICITY AND COMPARED TO THE CONTROL SURFACES PRODUCED IN (1). BISFUNCTIONAL PEO WILL BE COUPLED TO SURFACE AMINO GROUPS. BIOACTIVE MOLECULES WILL BE COUPLED VIA AMINO GROUPS TO THE SURFACE-BOUND PEO UNDER AQUEOUS CONDITIONS. ANALYSIS OFRADIOLABELED SURFACES WILL BE USED TO DETERMINE TOTAL AMOUNT OF IMMOBILIZED BIOACTIVE MOLECULES, AND BIOASSAY PROCEDURES THAT HAVE BEEN MODIFIED FOR SURFACE IMMOBILIZED COMPOUNDS WILL BE USED TO DETERMINE THEIR BIOACTIVITY AT THE INTERFACE. METHODOLOGY FOR MANUFACTURE OF MULTIFUNCTIONAL ANTITHROMBOGENIC SURFACES UNDER CONTROLLED CONDITINS WOULD SIGNIFICANTLY EXTEND THE EXISTINGTECHNOLOGY AVAILABLE FOR TREATING BLOOD-CONTACTING DEVICES TO RENDER THEM ANTITHROMBOGENIC AND THUS MORE HEMOCOMPATIBLE.