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变窄和阻塞，是发达国家的主要死因，约占加拿大死亡人数的五分之一。血管成形术是一种用于重新打开阻塞动脉而无需大手术的介入手术，是在阻塞动脉中重建血流的常见且有效的手术。在80%的病例中，在球囊血管成形术后将支架放置在血管中以保持其开放。尽管目前使用的支架在提供临床益处方面是优异的，但是由于有限的生物相容性，它们具有许多严重的缺点，导致支架阻塞和再狭窄。这反过来又导致患者生活质量下降、发病率增加和医疗保健费用增加。 我们建议开发一种更兼容的冠状动脉支架，通过修改最常用的不锈钢支架的表面与不可逆的固定和结构稳定的细胞外基质蛋白，纤连蛋白（FN）的单层。通过控制表面的物理化学性质，固定的FN将采用最有利于内皮细胞-材料相互作用的表面构象。我们假设FN改良支架的生物相容性将优于目前市场上可用的支架，这将降低再狭窄率，改善患者的生活质量，并降低医疗保健成本。 我们将使用先进的固体表面纳米结构化技术和方法，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.