Prohealing multifunctional endothelium nanomatrix coated stent

Prohealing多功能内皮纳米基质涂层支架

• 批准号: 8799777
• 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/8799777
• 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; 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; public health relevance; 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：支架是治疗心血管疾病最常用的心血管植入物。然而，人们担心裸金属支架（BMS）的支架内再狭窄和药物洗脱支架（DES）的晚期支架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，但仍存在许多新出现的问题和限制。开发创新策略以恢复内皮愈合，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，内皮是内皮细胞和下面的纳米纤维基底膜的薄层，其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。与支架展开相关的对这种多功能内皮的不可避免的损伤触发了再狭窄和血栓形成的级联反应。 本申请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，这将最大限度地降低晚期支架血栓形成、再狭窄、炎症反应和不完全内皮化的风险。本申请的总体假设是，促愈合多功能内皮纳米基质可以通过促进支架表面上的内皮愈合来增强支架的功效。 提出了三个具体目标来检验这一假设：具体目标1：评价内皮模拟、自组装纳米基质的多种组分的协同促愈合作用。具体目标二：采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涂层支架的影响。具体目标3：验证prohealing多功能内皮纳米基质涂层支架对离体兔动脉血管舒张和体内兔髂动脉球囊损伤模型中增强内皮愈合的有效性。这些目标提供了一种范式改变方法，将规避当前支架的重大医疗风险。