Endothelial Adhesion Molecules and Leukocyte Egress

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DESCRIPTION (provided by applicant): Approximately 80% of patients require an intravenous catheter upon hospitalization. Catheter-related infection comprises approximately half of all complications while catheter-induced thrombosis (fibrin sheath formation and mural thrombosis) compound 25% of all failures associated with catheter long-term presence in the vascular system. Blood compatible coatings have been investigated in recent years in order to improve material biocompatibility by reducing thrombogenicity through diminished protein adhesion. Numerous studies indicate that thrombogenic properties of a foreign surface can be significantly reduced by surface modifications. One of the more promising types of surface biolization technologies is a surfactant polymer coating (SPC) that attempts to mimic nature, in particular the properties of glycocalyx of vascular endothelium cells. It has been demonstrated through in vitro studies that SPC significantly reduces fibrinogen, and platelet adhesion and activation. Additional practical advantages of SPC are its low cost and simplicity of application to the surface of medical device. In Phase I, we determined the stability of the surfactant coating on polyurethane through in vitro shear studies corresponding to the shear rates experienced by a central venous catheter. Further, through series of ex vivo experiments using dog models, we determined that the SPC reduces fibrinogen and platelet adhesion to the coated surfaces. A reduction of over 80% of platelet adhesion to the SPC. was demonstrated in reference to non-coated medical grade polyurethane surfaces. This demonstrated the feasibility of SPCs for central venous catheters. The aim of Phase II research is to validate the biocompatibility of the coatings through in vivo studies in rats for long-term use. We will focus our investigation on two aspects: reduction of the fibrous sleeve on the catheter surface by SPC and reduction of catheter-related infections with SPC. After successful Phase II completion, we will be prepared to start human clinical trials and to finish the commercialization process.