Enhancement of biocompatibility of coronary stents by surface immobilization of fibronectin and controlled tailoring of protein-cell interactions

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Coronary artery disease, characterized by a progressive narrowing and blocking of blood vessels, is the leading cause of death in developed countries and accounts for about one fifth of the deaths in Canada. Angioplasty, which is an interventional procedure used for reopening blocked arteries without major surgery, is a common and effective procedure to reestablish blood flow in the blocked arteries. In 80% of cases, a stent is placed in the vessel to keep it open following the balloon angioplasty procedure. Although the stents currently in use are excellent in providing clinical benefits, they have many serious disadvantages resulting from limited biocompatibility, leading to stent blockage and restenosis. This, in turn, leads to a decline in the quality of life of the patient, increased morbidity rate and increased health care costs. We propose to develop a more compatible coronary stent by modifying the surface of the most commonly used stainless steel stent with an irreversibly immobilized and structurally stable monolayer of the extracellular matrix protein, fibronectin (FN). By controlled engineering of physico-chemical properties of the surface, the immobilized FN will adopt the surface conformation most favorable for endothelial cell-material interactions. We hypothesize that the FN-modified stent will be more biocompatible then stents currently available on the market, which will result in a decreased restenosis rate, improved quality of life of the patient, and decreased health-care costs. We will use advanced techniques and approaches for nano-structuring of solid surfaces to engineer the stent surface at a nano/molecular level in order to achieve the desired surface bio-physico-chemical properties. We will use a wide range of experimental techniques to investigate these properties, and perform a detailed analysis of the interaction of vascular smooth muscle cells and endothelial cells with the FN-modified surface. Ultimately, we will test the effectiveness of the FN-stent in vivo using an animal model.