Novel in situ custom biodegradable drug-eluting stents for endovascular surgery
用于血管内手术的新型原位定制可生物降解药物洗脱支架
基本信息
- 批准号:10663244
- 负责人:
- 金额:--
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2020
- 资助国家:美国
- 起止时间:2020-07-01 至 2024-12-31
- 项目状态:已结题
- 来源:
- 关键词:AcuteAdherenceAdhesionsAffectAreaArteriesAtherosclerosisBalloon AngioplastyBlood PlateletsBlood VesselsCardiacCardiovascular DiseasesCathetersCause of DeathCellsChemistryCitratesClinicalCustomDataDeveloped CountriesDevelopmentDiseaseDrug Delivery SystemsDrug usageElasticityEndothelial CellsEndotheliumEngineeringEnvironmentFDA approvedFailureFamily suidaeHealthHyperplasiaIn SituIn VitroIndividualIndustryInflammationInjuryInterventionLegal patentLiquid substanceLongitudinal StudiesMeasurableMetalsModificationModulusNitric OxideNitric Oxide DonorsOperative Surgical ProceduresPaclitaxelPatient-Focused OutcomesPeripheralPharmaceutical PreparationsPolymersProcessProliferatingProsthesisRadialResearch PersonnelS-NitrosothiolsSafetySecondary toSirolimusSiteSolidStentsSurfaceSystemTechnologyTestingThrombosisTimeTranslatingVasodilationVertebral columnVeteransbiodegradable polymerbiomaterial compatibilitycell growthcommon treatmentcostdesigndiazeniumdiolatedrug developmentflexibilityhealingimprovedin vivoinnovationmanufacturemechanical propertiesmilitary veteranmultidisciplinarynew technologynovelnovel strategiesphotopolymerizationporcine modelpreclinical studypreventprototyperestenosissafety studystent thrombosisthrombogenesis
项目摘要
Cardiovascular disease is the leading cause of death in developed countries. A common treatment for
atherosclerotic cardiovascular disease is placement of an arterial stent. While stent technology has improved
over the years, including the development of drug-eluting stents, failure rates remain high and current
technologies are associated with significant challenges. Thus, there is a great need for new stent technology
that will improve patient outcomes following percutaneous cardiac and peripheral vascular interventions. We
propose to develop an innovative, paradigm-shifting stent technology that will obviate the need for
placement of permanent metal stents in the arterial system for the treatment of severe atherosclerosis.
Specifically, we propose to develop a solid biodegradable stent from a liquid drug-eluting polymer by
photo-polymerizing the stent in the body using a specially designed triple balloon catheter. This
“designer therapy” will be tailored to the contours of the individual artery and coat the entire surface of the
artery, significantly reducing the thrombogenic potential at the site of injury and providing the greatest surface
area for drug delivery. Our biodegradable poly(dodecanediol citrate) (PDDC) stent will deliver nitric oxide
(NO), a vasoprotective molecule that will vasodilate the freshly angioplastied artery, thereby combating elastic
recoil. The custom-formed stent will also promote long-term vascular healing by simultaneously inhibiting
neointimal hyperplasia and platelet adhesion, and stimulating endothelial cell growth. The stent will have
mechanical properties specific for the pulsatile, compliant arterial system. Lastly, the stent will degrade over
time, leaving a healthy, prosthetic-free, polymer-free environment in its place. Thus, our hypothesis is that a
liquid-cast, NO-eluting, biodegradable stent will have a superior patency rate compared to
conventional metal stents following balloon angioplasty by inhibiting thrombosis and neointimal
hyperplasia, and stimulating re-endothelialization. Through our multidisciplinary team of investigators and
industry engineers, we have already demonstrated the feasibility of our project through preliminary data. It is
now time to focus on developing and optimizing the drug releasing capacity of the polymeric stent and
conducting the in vivo preclinical studies necessary to translate this technology to the clinical arena. Thus, the
specific aims of this project are: 1) Develop and optimize a NO-eluting, liquid-cast PDDC stent using
diazeniumdiolate and S-nitrosothiol chemistry; 2) Evaluate and tune the mechanical properties of the NO-
eluting, liquid-cast PDDC stent ex vivo; 3) Examine the safety and efficacy of the NO-eluting, liquid-cast PDDC
stent in vivo. Our novel approach challenges the existing paradigm for arterial stenting and will lead to a
radical departure in the treatment of atherosclerotic occlusive disease. Through our preliminary data, we have
demonstrated the feasibility of this project. Given the burden of atherosclerotic disease in the veteran
population, the studies in this proposal will result in a new technology that will be translated to improved
veteran health.
心血管疾病是发达国家的主要死亡原因。一种常见的治疗方法
动脉粥样硬化性心血管疾病是动脉支架的放置。虽然支架技术已经改进了
多年来,包括药物洗脱支架的开发,失败率仍然居高不下
技术与重大挑战相关。因此,非常需要新的支架技术。
这将改善经皮心脏和外周血管介入治疗后的患者预后。我们
建议开发一种创新的、范式转换的支架技术,该技术将不再需要
在动脉系统内放置永久性金属支架治疗严重的动脉粥样硬化。
具体地说,我们建议从液体药物洗脱聚合物中开发一种固体可生物降解支架,方法是
使用专门设计的三球囊导管在体内对支架进行光聚合。这
“设计者疗法”将针对单个动脉的轮廓而量身定做,并覆盖整个动脉表面。
动脉,显著降低损伤部位的血栓形成潜力,并提供最大的表面
药物投放区。我们的可生物降解的聚柠檬酸十二醇(PDDC)支架将释放一氧化氮
(NO),一种血管保护分子,将扩张新鲜的血管塑化的动脉,从而对抗弹性
后座力。定制的支架还将通过同时抑制血管愈合来促进长期血管愈合
新生内膜增生和血小板黏附,并刺激内皮细胞生长。支架将会有
脉动、顺应性动脉系统特有的机械特性。最后,支架会降解。
时间,留下一个健康的,没有假肢,没有聚合物的环境。因此,我们的假设是一个
液体浇铸、无洗脱、可生物降解支架的通畅率高于
球囊血管成形术后抑制血栓形成和新生内膜的传统金属支架
增殖,并刺激再内皮化。通过我们的多学科调查团队和
行业工程师们,我们已经通过初步数据论证了我们项目的可行性。它是
现在是时候专注于开发和优化聚合物支架的药物释放能力和
进行将这项技术转化为临床领域所需的体内临床前研究。因此,
本项目的具体目标是:1)开发和优化一种无洗脱、液态铸造的PDDC支架。
重氮尿苷和S-亚硝硫醇化学;2)评估和调整NO-2的力学性能。
体外洗脱液体浇铸PDDC支架;3)检测无洗脱液体浇铸PDDC支架的安全性和有效性
体内植入支架。我们的新方法挑战了现有的动脉支架植入模式,并将导致
动脉粥样硬化性闭塞症治疗中的根本背离。通过我们的初步数据,我们有
论证了该项目的可行性。考虑到退伍军人的动脉粥样硬化性疾病的负担
人口,这项建议中的研究将产生一种新技术,该技术将转化为改进
老兵健康。
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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Jose Francisco Huizar其他文献
Jose Francisco Huizar的其他文献
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{{ truncateString('Jose Francisco Huizar', 18)}}的其他基金
Research-Dedicated Magnetic Resonance Imaging at McGuire VA Medical Center
麦奎尔退伍军人医疗中心的研究专用磁共振成像
- 批准号:
10177717 - 财政年份:2020
- 资助金额:
-- - 项目类别:
Validation of Premature Ventricular Contraction-induced Cardiomyopathy on a Swine Model
在猪模型上验证室性早搏诱发的心肌病
- 批准号:
9892561 - 财政年份:2020
- 资助金额:
-- - 项目类别:
LV dyssynchrony and fibroblast activation in PVC-induced Cardiomyopathy
PVC 诱发的心肌病中左室不同步和成纤维细胞活化
- 批准号:
10669334 - 财政年份:2020
- 资助金额:
-- - 项目类别:
Validation of Premature Ventricular Contraction-induced Cardiomyopathy on a Swine Model
在猪模型上验证室性早搏诱发的心肌病
- 批准号:
10664914 - 财政年份:2020
- 资助金额:
-- - 项目类别:
Mechanistic Insights of Premature Ventricular Contractions-induced Cardiomyopathy
室性早搏诱发的心肌病的机制见解
- 批准号:
9922678 - 财政年份:2018
- 资助金额:
-- - 项目类别:
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