MOLECULAR BARRIERS TO BIOMATERIAL THROMBOSIS BY MODIFICATION OF SURFACE-PROTEINS WITH POLYETHYLENE-GLYCOL

For cardiovascular biomaterials, thrombosis, thromboembolism and vascu lar graft occlusion are believed to be precipitated by the adsorption of proteins containing adhesive ligands for platelets. Polyethylene-gl ycol-diisocyanate (PEG-diisocyanate, 3400 MW) may potentially react wi th protein amines to form molecular barriers on adsorbed proteins on b iomaterials, thereby masking adhesive ligands and preventing acute sur face thrombosis. To test this notion, PE, PTFE, and glass microconduit s were pre-adsorbed with fibrinogen and treated with PEG-diisocyanate, non-reactive PEG-dihydroxyl, or remained untreated. Following perfusi on of In-111-labeled platelets in whole human blood for 1 min (wall sh ear rate = 312 s(-1)), PEG-diisocyanate treated surfaces experienced 9 6% (PE), 97% (PTFE) and 94% (glass) less platelet deposition than untr eated surfaces. Similar reductions were seen for PEG-diisocyanate vers us PEG-dihydroxyl treatment. Low shear perfusions of plasma for 1 h pr ior to blood contact did not reduce the inhibitory effect of PEG-diiso cyanate. Platelet adhesion onto collagen-coated glass coverslips and p latelet deposition onto preclotted Dacron were also reduced by treatme nt with PEG-diisocyanate(93 and 91%, respectively). Protein-reactive P EG may thus have utility in forming molecular barriers on surface-asso ciated proteins to inhibit acute thrombosis on cardiovascular biomater ials. (C) 1998 Published by Elsevier Science Ltd. All rights reserved.