Prohealing multifunctional endothelium nanomatrix coated stent

描述：支架是治疗心血管疾病最常用的心血管植入物。然而，对于裸金属支架（BMS）的支架内再狭窄以及药物洗脱支架（DES）的支架晚期血栓形成和晚期炎症反应存在担忧。尽管最近开发的策略有望克服当前支架的挑战，但仍有许多新出现的问题和局限性。开发创新的策略来恢复内皮愈合，同时限制晚期支架血栓形成、炎症反应和再狭窄的风险，对于支架的长期成功至关重要。在自然界中，内皮是由内皮细胞和下面的纳米纤维基膜组成的薄层，通过释放可溶性因子，如一氧化氮（NO）来调节血管张力。内皮功能障碍或内皮损伤是血管疾病的标志之一。与支架部署相关的对多功能内皮的不可避免的损伤引发了再狭窄和血栓形成的级联。这项应用的目的是证明新型多功能内皮纳米基质涂层支架的促愈合作用，它将最大限度地降低支架晚期血栓形成、再狭窄、炎症反应和不完全内皮化的风险。本应用的总体假设是促愈合多功能内皮纳米基质可以通过促进支架表面内皮细胞的愈合来增强支架的功效。为了验证这一假设，我们提出了三个具体目标：具体目标1：评估多种模拟内皮细胞的自组装纳米基质的协同促愈合作用。目的2：利用兔动脉模拟生物反应器，研究血流动力学对促愈合多功能内皮纳米基质包被支架的影响。目的3：在兔髂动脉球囊损伤模型中，验证促愈合多功能内皮纳米基质包被支架在体外对兔动脉血管舒张和内皮细胞愈合的促进作用。这些目标提供了一种改变范式的方法，可以规避当前支架的重大医疗风险。

DESCRIPTION: Stents are the most common cardiovascular implants used in the treatment of cardiovascular diseases. However, there are concerns about in-stent restenosis with bare metal stents (BMS) and late stent thrombosis and late inflammatory responses with drug-eluting stents (DES). Despite the promise of recently developed strategies to overcome the challenges of current stents, there remain many emerging concerns and limitations. Development of innovative strategies to restore endothelial healing while limiting the risk of late stent thrombosis, inflammatory responses, and restenosis is critical for the long-term success of stents. In nature, the endothelium is the thin layer of endothelial cells and underlying nanofibrillar basement membrane that modulates vascular tone by release of soluble factors, such as nitric oxide (NO). Endothelial dysfunction or the injury of endothelium is a hallmark of vascular diseases. The inevitable injury to this multifunctional endothelium associated with stent deployment triggers the cascade of restenosis and thrombosis. The goal of this application is to demonstrate the prohealing effects of the novel multifunctional endothelium nanomatrix coated stent, which will minimize the risks of late stent thrombosis, restenosis, inflammatory responses, and incomplete endothelialization. The overall hypothesis of this application is that the prohealing multifunctional endothelium nanomatrix can enhance the efficacy of the stent by promoting endothelial healing on the surface of the stent. Three specific aims are proposed to test this hypothesis: Specific Aim 1: To evaluate the synergistic prohealing effects of multiple components of the endothelium mimicking, self-assembled nanomatrix. Specific Aim 2: To determine the influence of hemodynamics on the prohealing multifunctional endothelium nanomatrix coated stent using a rabbit artery simulating bioreactor. Specific Aim 3: To validate the efficacy of the prohealing multifunctional endothelium nanomatrix coated stent on vasodilation of rabbit arteries ex vivo and enhanced endothelial healing in a rabbit iliac artery balloon injury model in vivo. These aims provide a paradigm changing approach that will circumvent the significant healthcare risks of current stents.