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

冠状动脉疾病的特点是血管逐渐狭窄和阻塞，是发达国家的主要死亡原因，约占加拿大死亡人数的五分之一。血管成形术是一种无需大手术即可重新打开阻塞动脉的介入性手术，是一种常见且有效的重建阻塞动脉血流的方法。在80%的病例中，在球囊血管成形术后，在血管中放置支架以保持血管开放。虽然目前使用的支架具有良好的临床疗效，但由于生物相容性有限，存在许多严重的缺点，导致支架堵塞和再狭窄。这又导致病人的生活质量下降，发病率增加，保健费用增加。我们建议用细胞外基质蛋白纤维连接蛋白（FN）的不可逆固定和结构稳定的单层来修饰最常用的不锈钢支架的表面，以开发一种更兼容的冠状动脉支架。通过对表面物理化学性质的工程控制，固定化FN将采用最有利于内皮细胞-物质相互作用的表面构象。我们假设fn修饰支架将比目前市场上可用的支架具有更好的生物相容性，这将导致再狭窄率降低，患者的生活质量提高，并降低医疗保健费用。我们将采用先进的固体表面纳米结构技术和方法，在纳米/分子水平上设计支架表面，以实现所需的表面生物物理化学特性。我们将使用广泛的实验技术来研究这些特性，并对血管平滑肌细胞和内皮细胞与fn修饰表面的相互作用进行详细分析。最终，我们将使用动物模型在体内测试fn支架的有效性。

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.