For cardiovascular
biomaterials,
thrombosis,
thromboembolism and
vascular graft occlusion are believed to be precipitated by the adsorption of
proteins containing adhesive
ligands for platelets.
Polyethylene-glycol-diisocyanate (
PEG-diisocyanate, 3400 MW) may potentially react with
protein amines to form molecular barriers on adsorbed
proteins on
biomaterials, thereby masking adhesive
ligands and preventing acute surface
thrombosis. To test this notion, PE,
PTFE, and glass microconduits were pre-adsorbed with
fibrinogen and treated with
PEG-diisocyanate, non-reactive
PEG-dihydroxyl, or remained untreated. Following perfusion of 111In-labeled platelets in whole human blood for 1 min (wall shear rate = 312 s(-1)),
PEG-diisocyanate treated surfaces experienced 96% (PE), 97% (
PTFE) and 94% (glass) less platelet deposition than untreated surfaces. Similar reductions were seen for
PEG-diisocyanate versus
PEG-dihydroxyl treatment. Low shear perfusions of plasma for 1 h prior to blood contact did not reduce the inhibitory effect of
PEG-diisocyanate. Platelet adhesion onto
collagen-coated glass coverslips and platelet deposition onto preclotted
Dacron were also reduced by treatment with
PEG-diisocyanate (93 and 91%, respectively).
Protein-reactive PEG may thus have utility in forming molecular barriers on surface-associated
proteins to inhibit acute
thrombosis on cardiovascular
biomaterials.