Catalytic Nitric Oxide Release Coating for Prolonged Anti-Clotting Catheters

描述：每年数十亿美元的医疗保健费用用于临床实践中失败的医疗设备。这些器械失效发生在器械的不同时间尺度上，并且是由于多种因素造成的，包括血栓形成、炎症、感染和植入器械表面上的组织过度生长以及机械器械失效。在过去的50年里，人们对这些器械失效有了很多了解，并尝试使用（1）替代性全身药物治疗，（2）器械表面改性，或 (3)两种方法的结合。尽管努力提高血液接触和可植入医疗装置的功效，但这些材料在人体血液和组织内的不相容性仍会导致患者严重的并发症。因此，全身或局部药物治疗，如肝素仍然是必要的。因此，可以利用天然存在的生物制剂（如一氧化氮（NO））的生物学特性的策略对各种医疗器械具有明确的意义。这些材料仅在靶向生物活性的血液-材料界面处提供局部功能控制。本研究的战略重点是开发材料，可以从内源性来源产生NO的时间延长，并将克服目前NO材料的根本局限性。使用金属有机框架（MOFs）作为NO催化剂，设备涂层现在将能够（1）产生显着高水平的一氧化氮和（2）允许系统性修饰，同时保持使其适用于临床应用的结构特性。因此，我们认为， 本研究的主要目的是利用MOF材料的固有结构特征来开发与生理相关的NO催化剂。作为这项探索性资助的一部分，新的MOF将被制备，混合到设备涂层中，并对其长期功能和机械性能进行严格测试，最后通过毒性研究评估安全性，并通过一系列体外生物测定进行表征。所进行的研究的结果将用于将最有前途的复合制剂转化为未来的体内模型。

DESCRIPTION: 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 and are 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 and attempts have been made 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 function only at the blood-material interface where bioactivity is targeted. The strategy of this research 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 significantly high levels of nitric oxide and (2) allow systematic modification while maintaining the structural properties that make them suitable for clinical applications. Therefore, the principal premise of this project investigator is to utilize the inherent structural features o MOF materials to develop physiologically-relevant NO catalysts. As a part of this exploratory grant, the new MOFs will be prepared, blended into device coatings and rigorously tested for their long-term function and mechanical properties, and finally evaluated for safety via toxicity studies and characterized by an array of in vitro bioassays. The outcomes of the studies performed will be used to translate the most promising composite formulations to future in vivo models.