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首要死因。一种常见的治疗方法是
动脉粥样硬化性心血管疾病是指放置动脉支架。虽然支架技术已经进步
多年来,包括药物洗脱支架的开发,失败率仍然很高,目前
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
提议开发一种创新的、范式转变的支架技术,该技术将消除对
在动脉系统中放置永久性金属支架以治疗严重动脉粥样硬化。
具体来说,我们建议通过液体药物洗脱聚合物开发固体可生物降解支架
使用专门设计的三球囊导管对体内支架进行光聚合。这
“设计师疗法”将根据单个动脉的轮廓进行定制,并覆盖整个动脉表面
动脉,显着降低受伤部位的血栓形成可能性并提供最大的表面
药物输送区域。我们的可生物降解聚(十二烷二醇柠檬酸酯)(PDDC)支架将输送一氧化氮
(NO),一种血管保护分子,可以舒张新血管成形的动脉,从而对抗弹性
畏缩。定制支架还将通过同时抑制血管损伤来促进长期血管愈合。
新内膜增生和血小板粘附,并刺激内皮细胞生长。支架将具有
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、无假肢、无聚合物的环境。因此,我们的假设是
与相比,液铸、NO 洗脱、可生物降解的支架具有更高的通畅率
球囊血管成形术后的传统金属支架通过抑制血栓形成和新生内膜
增生,并刺激再内皮化。通过我们的多学科研究团队和
行业工程师,我们已经通过初步数据论证了我们项目的可行性。这是
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,
该项目的具体目标是: 1) 开发并优化 NO 洗脱、液铸 PDDC 支架
二醇二氮烯鎓和 S-亚硝基硫醇化学; 2) 评估和调整NO-的机械性能
离体洗脱、液铸 PDDC 支架; 3) 检查 NO 洗脱液铸 PDDC 的安全性和有效性
体内支架。我们的新颖方法挑战了现有的动脉支架植入范式,并将导致
彻底改变动脉粥样硬化闭塞性疾病的治疗方法。通过我们的初步数据,我们有
论证了该项目的可行性。考虑到退伍军人动脉粥样硬化疾病的负担
人口,本提案中的研究将产生一项新技术,该技术将转化为改进的
退伍军人健康。
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)
数据更新时间:{{ journalArticles.updateTime }}
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
数据更新时间:{{ journalArticles.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ monograph.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ sciAawards.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ conferencePapers.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ patent.updateTime }}
Jose Francisco Huizar其他文献
Jose Francisco Huizar的其他文献
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
{{ 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:
相似海外基金
An innovative, AI-driven prehabilitation platform that increases adherence, enhances post-treatment outcomes by at least 50%, and provides cost savings of 95%.
%20创新、%20AI驱动%20康复%20平台%20%20增加%20依从性、%20增强%20治疗后%20结果%20by%20at%20至少%2050%、%20和%20提供%20成本%20节省%20of%2095%
- 批准号:
10057526 - 财政年份:2023
- 资助金额:
-- - 项目类别:
Grant for R&D
Improving Repositioning Adherence in Home Care: Supporting Pressure Injury Care and Prevention
提高家庭护理中的重新定位依从性:支持压力损伤护理和预防
- 批准号:
490105 - 财政年份:2023
- 资助金额:
-- - 项目类别:
Operating Grants
Unintrusive Pediatric Logging Orthotic Adherence Device: UPLOAD
非侵入式儿科记录矫形器粘附装置:上传
- 批准号:
10821172 - 财政年份:2023
- 资助金额:
-- - 项目类别:
Nuestro Sueno: Cultural Adaptation of a Couples Intervention to Improve PAP Adherence and Sleep Health Among Latino Couples with Implications for Alzheimer’s Disease Risk
Nuestro Sueno:夫妻干预措施的文化适应,以改善拉丁裔夫妇的 PAP 依从性和睡眠健康,对阿尔茨海默病风险产生影响
- 批准号:
10766947 - 财政年份:2023
- 资助金额:
-- - 项目类别:
CO-LEADER: Intervention to Improve Patient-Provider Communication and Medication Adherence among Patients with Systemic Lupus Erythematosus
共同领导者:改善系统性红斑狼疮患者的医患沟通和药物依从性的干预措施
- 批准号:
10772887 - 财政年份:2023
- 资助金额:
-- - 项目类别:
Pharmacy-led Transitions of Care Intervention to Address System-Level Barriers and Improve Medication Adherence in Socioeconomically Disadvantaged Populations
药房主导的护理干预转型,以解决系统层面的障碍并提高社会经济弱势群体的药物依从性
- 批准号:
10594350 - 财政年份:2023
- 资助金额:
-- - 项目类别:
Antiretroviral therapy adherence and exploratory proteomics in virally suppressed people with HIV and stroke
病毒抑制的艾滋病毒和中风患者的抗逆转录病毒治疗依从性和探索性蛋白质组学
- 批准号:
10748465 - 财政年份:2023
- 资助金额:
-- - 项目类别:
Improving medication adherence and disease control for patients with multimorbidity: the role of price transparency tools
提高多病患者的药物依从性和疾病控制:价格透明度工具的作用
- 批准号:
10591441 - 财政年份:2023
- 资助金额:
-- - 项目类别:
Development and implementation of peer-facilitated decision-making and referral support to increase uptake and adherence to HIV pre-exposure prophylaxis in African Caribbean and Black communities in Ontario
制定和实施同行协助决策和转介支持,以提高非洲加勒比地区和安大略省黑人社区对艾滋病毒暴露前预防的接受和依从性
- 批准号:
491109 - 财政年份:2023
- 资助金额:
-- - 项目类别:
Fellowship Programs