Molecular barriers to thrombosis formed with protein reactive polyethylene glycol

This thesis describes the development and testing of a technique for the formation of molecular barriers which are resistant to platelet adhesion using protein reactive polyethylene glycol. Following angioplasty, growth factors and enzymes released from depositing platelets are thought to lead to the hyperplastic response which causes restenosis in 30-40% of vessels successfully revascularized. Molecular barriers will be formed by an end activated form of polyethylene glycol (PEG) which is reactive to proteins on the vessel surface. PEG modification of proteins in solution extends their serum half-life and decreases their immunogenicity. PEG modification of biomaterial surfaces has often resulted in vastly improved blood compatibility properties attributable to a resistance to protein adsorption.;In vitro experiments have demonstrated that PEG-ISO modification can reduce platelet deposition onto damaged placental arteries by 87 +/;Another potential application of this surface protein modification technique is in the area of biomaterials. The first step upon exposure of any biomaterial to blood is plasma protein adsorption which often leads to platelet adhesion. By allowing a controlled exposure of a biomaterial to proteins and then treating the adsorbed proteins with PEG-DISO, we hypothesized that a platelet resistant molecular can be created. We have demonstrated that PEG-DISO modification decreased platelet deposition onto fibrinogen treated PE and PTFE by 97% and 98% respectively. Furthermore, the reduction in platelet deposition onto PEG-DISO treated tubes was not diminished following 1 hour plasma contact indicating that the barrier is non-fouling in this time period.;These data indicate that PEG-DISO modification could be a powerful tool in improving biocompatibility of devices for acute cardiovascular applications. Also, PEG modification of damaged arterial surfaces could be a powerful weapon in fighting intimal hyperplasia.