Metal organic framework-based antithrombotic surfaces

摘要： 每年，数十亿美元的医疗保健资金被花费在临床实践中失败的医疗设备上。这些 由于包括血栓在内的多种因素，设备故障在设备的各种时间尺度上发生， 植入物表面的炎症、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)替代全身药物疗法，(2)表面治疗来防止失败 对设备进行修改，或(3)两种方法的组合。尽管努力改善 血液接触和植入性医疗器械的有效性，这些材料在体内的不相容 人类的血液和组织仍然会给患者带来严重的并发症。因此，全身性或区域性药物 肝素等疗法仍然是必要的。因此，能够利用生物多样性的战略 自然产生的生物制剂的性质，如一氧化氮(NO)，对广泛的 各种医疗器械。这些材料提供了对血液-材料界面上的血小板的局部控制 生物活性为目标的地方。文中详述的研究策略侧重于开发材料 可以在很长一段时间内从内源性来源产生NO，并将克服 目前无材料的基本限制。使用金属有机骨架(MOF)作为无催化剂， 设备涂层现在将能够(1)生产的时间不会比到目前为止所达到的时间更长，以及(2) 允许系统修改，同时保持结构属性，使其适合 临床应用。本项目提案的主要前提是利用固有的结构形式 MOF材料的特点，以开发用于导管涂层的生理相关NO催化剂。作为一名 作为这笔赠款的一部分，MOF将被制备、混合到导管涂层中并进行严格的长期测试。 术语功能和机械性能，通过毒性研究评估安全性，并以 一系列体外生物检测。最终的导管原型将在兔模型中进行抗血栓测试 属性的时间点超出了当前技术的能力范围。

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.