Metal organic framework-based antithrombotic surfaces

基于金属有机骨架的抗血栓表面

• 批准号: 9922365
• 负责人: Hitesh Handa
• 金额: $ 35.95万
• 依托单位: COLORADO STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-05-01 至 2022-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9922365
• 关键词: Achievement; Acute; Address; Animal Model; Anticoagulants; Biochemical; Biological; Biological Process; Blood; Blood Platelets; Blood Pressure; Catheters; Cell Culture Techniques; Cellular Assay; Cessation of life; Chronic; Coagulation Process; Conscious; Copper; Critical Illness; Custom; Devices; Equipment Malfunction; Evaluation; Failure; Functional disorder; Grant; Half-Life; Health Expenditures; Healthcare; Hemostatic function; Heparin; Hepatocyte; Human; In Vitro; Inductively Coupled Plasma Mass Spectrometry; Infection; Inflammation; Intravenous; Ions; Lead; Length; Measures; Mechanics; Medical Device; Metals; Methemoglobin; Modeling; Modification; Morbidity - disease rate; Nature; Nitric Oxide; Nitric Oxide Donors; Oryctolagus cuniculus; Patient Care; Patients; Performance; Pharmacotherapy; Physiological; Platelet Activation; Polymers; Polyurethanes; Pre-Clinical Model; Production; Property; Research; S-Nitrosothiols; Safety; Silicone Elastomers; Source; Spectrum Analysis; Stream; Structure; Surface; System; Techniques; Technology; Testing; Therapeutic; Therapeutic Agents; Thrombosis; Thrombus; Time; Tissues; Toxic effect; Translations; Work; base; catalyst; chemical property; clinical application; clinical practice; clinically relevant; clinically significant; design; dosage; experimental study; hemocompatibility; implantable device; improved; in vitro Assay; in vitro Bioassay; in vitro Model; in vivo; mechanical device; mechanical properties; novel; novel strategies; patient population; platelet function; prevent; prototype; side effect; standard of care; therapeutic target

ABSTRACT: Each year billions of health care dollars are spent on medical devices that fail in clinical practice. These device failures occur over various timescales of the devices due to multiple factors including thrombosis, inflammation, infection, and tissue overgrowth on the surface of the implanted device as well as mechanical device failures. Over the last 50 years, much has been learned about these device failures resulting in attempts to prevent failures using (1) alternative systemic drug therapies, (2) surface modifications on the device, or (3) a combination of both approaches. Despite efforts to improve the efficacy of blood-contacting and implantable medical devices, the incompatibility of these materials within human blood and tissue still causes serious complications in patients. Thus, systemic or regional drug therapies such as heparin remain necessary. As a result, strategies that can leverage the biological properties of naturally occurring bioagents such as nitric oxide (NO) have clear implications for a wide variety of medical devices. These materials offer localized control of platelets at the blood-material interface where bioactivity is targeted. The research strategy detailed here in focuses on developing materials that can produce NO from endogenous sources for extended periods of time and will overcome the fundamental limitations of current NO materials. Using metal organic frameworks (MOFs) as NO catalysts, device coatings will now be able to (1) produce NO for longer time period than ever achieved to date and (2) allow systematic modification while maintaining the structural properties that make them suitable for clinical applications. The principal premise of this project proposal is to utilize the inherent structural features of MOF materials to develop physiologically-relevant NO catalysts for use in catheter coatings. As a part of this grant, MOFs will be prepared, blended into catheter coatings and rigorously tested for their long- term function and mechanical properties, evaluated for safety via toxicity studies and characterized by an array of in vitro bioassays. Final catheter prototypes will be tested in a rabbit model for their anti-thrombotic properties at time points beyond the capabilities of current technologies.

摘要： 每年，数十亿美元的医疗保健费用花费在临床实践中失败的医疗设备上。这些 由于多种因素包括血栓形成， 植入器械表面的炎症、感染和组织过度生长，以及 机械设备故障。在过去的50年里，人们对这些设备故障有了很多了解 导致尝试使用（1）替代性全身药物疗法，（2）表面 对设备进行修改，或（3）两种方法的组合。尽管努力改善 血液接触和植入式医疗器械的有效性，这些材料在 人体血液和组织仍会导致患者出现严重并发症。因此，全身性或区域性药物 仍然需要诸如肝素的治疗。因此，可以利用生物学的策略 天然存在的生物制剂如一氧化氮（NO）的性质对广泛的生物制剂具有明确的意义。 各种医疗器械。这些材料在血液-材料界面处提供血小板的局部控制 其中生物活性是目标。这里详细介绍的研究策略侧重于开发材料 它可以从内源性来源产生NO持续很长一段时间，并将克服 目前NO材料的基本局限性。使用金属有机骨架（MOFs）作为NO催化剂， 器件涂层现在将能够（1）比迄今为止所实现的更长时间地产生NO，以及（2） 允许系统的修改，同时保持结构特性，使他们适合 临床应用。本项目建议书的主要前提是利用固有的结构 本发明的目的是利用MOF材料的特性来开发用于导管涂层的生理学相关的NO催化剂。作为 作为该补助金的一部分，将制备MOFs，将其混合到导管涂层中，并对其长期性能进行严格测试， 术语功能和机械性能，通过毒性研究评估安全性，并通过 一系列体外生物测定。最终导管原型将在家兔模型中进行抗血栓形成试验 在超出当前技术能力的时间点的特性。