Prohealing multifunctional endothelium nanomatrix coated stent

Prohealing多功能内皮纳米基质涂层支架

• 批准号: 8994745
• 负责人: Ho-Wook Jun
• 金额: $ 35.9万
• 依托单位: UNIVERSITY OF ALABAMA AT BIRMINGHAM
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-01-15 至 2019-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8994745
• 关键词: Address; Adhesions; Angiography; Arteries; Basement membrane; Biochemical Pathway; Biological; Bioreactors; Blood Platelets; Blood Vessels; Cardiovascular Diseases; Cardiovascular system; Cell Proliferation; Characteristics; Chemicals; Clinical; Development; Endothelial Cells; Endothelium; Environment; Evaluation; Extracellular Matrix; FDA approved; Goals; Healed; Health; Healthcare; Histology; Hyperplasia; Immunohistochemistry; Implant; Inflammation; Inflammatory Response; Injury; Lead; Measurement; Metals; Modeling; Nature; Nitric Oxide; Organic solvent product; Oryctolagus cuniculus; Outcome; Peptides; Pharmaceutical Preparations; Polymers; Production; Property; Recruitment Activity; Reporting; Risk; Smooth Muscle Myocytes; Stem cells; Stents; Surface; Testing; Thrombosis; Time; Tissues; United States; Validation; Vascular Diseases; Vasodilation; biomaterial compatibility; design; endothelial dysfunction; experience; healing; hemodynamics; high risk; iliac artery; implantable device; in vivo; in vivo Model; innovation; insight; morphometry; novel; response; restenosis; shear stress; stent thrombosis; success

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.

描述：支架是最常见的心血管植入物，用于治疗心血管疾病。然而，人们担心裸金属支架(BMS)支架内再狭窄和药物洗脱支架(DES)支架晚期血栓形成和晚期炎症反应。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担忧和限制。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，是支架长期成功的关键。在自然界中，内皮是一层薄薄的内皮细胞和底层的纳米纤维基底膜，通过释放一氧化氮(NO)等可溶性因子来调节血管张力。内皮功能障碍或内皮损伤是血管疾病的标志。支架置入对这种多功能内皮的不可避免的损伤会触发再狭窄和血栓的级联反应。本应用的目的是证明新型多功能内皮纳米基质涂层支架的愈合效果，它将把晚期支架血栓形成、再狭窄、炎症反应和不完全内皮化的风险降至最低。这一应用的总体假设是，促愈合的多功能内皮纳米基质可以通过促进支架表面的内皮愈合来增强支架的疗效。提出了三个特定的目标来验证这一假设：特定的目标1：评估模仿内皮的多个组件的协同促进愈合效果，自组装的纳米基质。具体目的2：利用兔动脉模拟生物反应器，研究血流动力学对多功能内皮纳米基质涂层支架形成的影响。具体目的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涂层支架对兔动脉血管的体外扩张和促进内皮愈合的作用。这些目标提供了一种改变范式的方法，将绕过当前支架的重大医疗风险。