Studies on the interactions of tissue plasminogen activator (tPA) and plasminogen with polyurethane surfaces containing epsilon-lysine moieties (epsilon-amino group free) are reported. These surfaces are considered to have the potential to dissolve nascent clots that may be formed on them. For adsorption from both single protein solutions and plasma, the surfaces were found to have a high capacity for tPA as well as plasminogen. A significant fraction of preadsorbed tPA was displaced from the epsilon-lysine surfaces upon contact with plasma. These surfaces, when preadsorbed with tPA and then incubated with plasma, were able to dissolve incipient clots formed around them. However, the clot-dissolving capacity diminished as the time of plasma incubation increased, presumably due to loss of tPA. It was also shown that in plasma, preadsorbed tPA is displaced from these surfaces largely by plasminogen, which thus appears to have a greater binding affinity than tPA for the epsilon-lysine moieties. Finally, it was found that in plasma, the epsilon-lysine surfaces interact with plasminogen in a dynamic manner, and that about 70% of the bound plasminogen is exchanging continuously with plasminogen in the plasma.

This article reports on the concept of a fibrinolytic surface based on the preferential adsorption of endogenous plasminogen from blood. Data are presented indicating that such a surface, when pretreated with tissue-type plasminogen activator (tPA), is able to dissolve nascent thrombus generated in contact with flowing whole blood. Polyethylene (PE) surfaces were modified by attaching a lysine-containing polymer using photochemical methods as reported previously (McClung et al., J Biomed Mater Res 2000;49:409-414). The lysine residues were bound chemically to the polymer via the a-amino groups leaving the e-amino groups free (e-Lys surface). Control surfaces were (a) unmodified PE, (b) PE modified with the coating polymer containing no lysine, and (c) PE modified with the polymer containing lysine bound via the e-amino group. The materials in tubing form were evaluated in contact with nonanticoagulated flowing human whole blood in a modified Chandler Loop experiment. They were first treated with tPA to allow activation of adsorbed plasminogen to plasmin. It was found that thrombus formation was initiated within 15-25 min (depending on donor blood) on all surfaces, as indicated by the formation of platelet aggregates. On the controls (including the lysine-containing material in which the e-amino group was used in the binding reaction) thrombogenesis continued till the tubing was occluded and blood flow ceased. On the eLys surface, thrombogenesis was interrupted at various stages depending on the donor blood; in all cases any thrombus generated was dissolved within minutes. It was shown that thrombolysis was due to the fibrinolytic action of plasmin generated at the surface and not to plasmin formed by traces of tPA released into the blood. This work provides further evidence of the efficacy of this approach to the development of a fibrinolytic surface. 2006 Wiley Periodicals, Inc. J Biomed Mater Res 81A: [644][645][646][647][648][649][650][651] 2007