Metal organic framework-based antithrombotic surfaces

基于金属有机骨架的抗血栓表面

基本信息

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
项目类别：
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

项目摘要

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.

抽象的：每年的保健资金每年都花在临床实践中失败的医疗设备上。这些由于多个因素，包括血栓形成，植入装置表面的炎症，感染和组织过度生长以及机械设备故障。在过去的50年中，有关这些设备故障的知识已有很多导致尝试使用（1）替代全身药物疗法的尝试防止失败，（2）表面设备上的修改，或（3）两种方法的组合。尽管努力改善血液接触和可植入医疗设备的功效，这些材料不兼容人体血液和组织仍会导致患者严重并发症。因此，全身或区域药物诸如肝素之类的疗法仍然是必要的。结果，可以利用生物学的策略一氧化氮（NO）等自然生物代理人的特性对宽阔的影响有明显的影响各种医疗设备。这些材料在血液材料接口处提供了血小板的局部控制生物活性的目标。此处详细介绍的研究策略重点是开发材料可以长时间的内源性来源产生任何来自内源性的来源，并将克服当前无材料的基本局限性。将金属有机框架（MOF）作为无催化剂，现在，设备涂料将能够（1）持续时间比迄今为止的时间更长，并且（2）允许系统的修改，同时保持结构属性使其适合于临床应用。该项目建议的主要前提是利用固有的结构 MOF材料的特征是开发与生理相关的无催化剂用于导管涂层的特征。作为该赠款的一部分，将准备MOF，将其混合成导管涂层，并严格测试其长期期限功能和机械性能，通过毒性研究评估安全性，并以体外生物测定阵列。最终导管原型将在兔模型中测试其抗栓性时间点的属性超出了当前技术的功能。