CAREER:Metal Organic Frameworks for Increased Nitric Oxide Duration at Medical Interfaces Plus the Development of a Biomaterials Module for Non-STEM Majors

职业：用于增加医疗接口中一氧化氮持续时间的金属有机框架以及针对非 STEM 专业的生物材料模块的开发

• 批准号: 1352201
• 负责人: Melissa Reynolds
• 金额: $ 50万
• 依托单位: Colorado State University
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-06-01 至 2019-05-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1352201&HistoricalAwards=false
• 关键词: CAREER; Metal; Organic; Frameworks; Increased

Non-technical:The goal of this research project is to develop methodologies for therapeutic materials which can be utilized in medical devices. At present, infection and clotting caused by long-term medical implants such as stents, catheters, and grafts, can compromise patient care and contribute to increased health care costs. Currently, no therapeutics are available that can be used in the manufacturing of medical devices which will last the lifetime of the implant. In this work, a completely new approach in creating materials for long-term medical devices is proposed that uses catalysts to produce natural therapeutic agents after a device has been implanted in a patient. The materials chosen can be quickly integrated into current manufacturing processes and, thereby, reduce retooling costs and expedite the time to market for next generation medical devices. Most importantly, the results of this work will reduce the necessity for patients with long-term medical implants to undergo repeated surgeries due to common failures of current devices. A direct result of this work will be quality training of undergraduate and graduate students in interdisciplinary and cutting-edge biomedical research. In addition, the proposed work also helps college students to become more informed citizens through the development of a biomaterials teaching module for undergraduates. This module will promote informed citizens by providing students with an understanding of the challenges faced by biomedical researchers and manufacturers when bringing new medical innovations to market.Technical:This CAREER award by the Biomaterials program in the Division of Materials Research to Colorado State University will focus on developing a new class of biomaterials that can extend the lifetime of implants used for long periods. This award is cofunded by the Biotechnology, Biochemical, and Biomass Engineering program in the Division of Chemical, Bioengineering, Environmental, and Transport Systems. To date, the lifetime of the implants is limited due to the incompatibility between the device and surrounding fluids and cells, inflammation and possible infection. To prevent such incompatibilities and promote integration of the device into the body without compromising its functional properties, a novel strategy is proposed that uses metal organic framework (MOF) catalysts, which endogenously generate nitric oxide (NO). Nitric oxide is a well-established bioregulatory agent, and is known to prevent clotting and infection while promoting cell growth. The synthesis and subsequent incorporation of catalytic amounts of tailored NO releasing materials at the biointerface minimizes the likelihood for adverse alterations to the physical or mechanical properties of implants. Thus, this unique strategy allows for translation to a range of applications that require NO dosages that were not previously possible. In this project, the researcher will explore how the structure of the catalyst influences its reactivity with various S-nitrosothiols (RSNOs) to locally produce NO at the polymer interface. Further, other important factors such as polymer matrix and processing methods will be evaluated to fine tune the dosages of NO produced at the surface. The project is expected to produce new methodologies for therapeutic additives, and develop a better fundamental understanding of how these materials can function as biologically useful catalysts. In doing so, this work utilizes MOF catalysts in a manner not used previously. As such, this work not only advances the field of biomaterials, but also that of metal organic framework catalysis. The broader impact focus of this project is in the development and training of students in the field of biomaterials by exposing them to a broad range of perspectives and approaches that makes them ready to work in various environments when they graduate from college. This includes students being able to work either independently or in collaborative research teams and to understand how their expertise contributes to the overall success of the project. In addition, biomaterial modules for non-science majors will be developed and implemented into the undergraduate laboratory curriculum to improve student awareness of biomaterials. The curriculum module being developed will explicitly focus on questions related to biomaterials, their discovery, and how a material could be used for biomedical applications. To understand the effectiveness of this new module, pre- and post-surveys will be used to evaluate student demographics, student motivations, student views about the nature of science, and students' learning abilities.

非技术性：本研究项目的目标是开发可用于医疗器械的治疗材料的方法。目前，由长期医疗植入物（如支架、导管和移植物）引起的感染和凝血会损害患者护理并导致医疗保健成本增加。目前，没有治疗剂可用于制造将持续植入物寿命的医疗器械。在这项工作中，提出了一种全新的方法来制造长期医疗设备的材料，该方法在设备植入患者体内后使用催化剂来产生天然治疗剂。所选择的材料可以快速集成到当前的制造工艺中，从而降低重新加工成本，加快下一代医疗器械的上市时间。最重要的是，这项工作的结果将减少由于当前设备的常见故障而导致长期医疗植入物患者接受重复手术的必要性。这项工作的一个直接结果将是对本科生和研究生进行跨学科和尖端生物医学研究的质量培训。此外，拟议的工作也有助于大学生成为更知情的公民，通过发展的本科生生物材料教学模块。该模块将通过让学生了解生物医学研究人员和制造商在将新的医疗创新推向市场时所面临的挑战，促进知情公民。技术：该职业奖由科罗拉多州立大学材料研究部的生物材料项目授予，重点是开发一类新的生物材料，可以延长长期使用的植入物的寿命。该奖项由化学，生物工程，环境和运输系统部门的生物技术，生物化学和生物质工程项目共同资助。迄今为止，由于器械与周围液体和细胞之间的不相容性、炎症和可能的感染，植入物的寿命有限。为了防止这种不相容性，并促进设备整合到体内，而不损害其功能特性，提出了一种新的策略，使用金属有机框架（MOF）催化剂，内源性产生一氧化氮（NO）。一氧化氮是一种公认的生物调节剂，已知可防止凝血和感染，同时促进细胞生长。在生物界面处合成并随后掺入催化量的定制的NO释放材料使植入物的物理或机械性质的不利改变的可能性最小化。因此，这种独特的策略允许转化为一系列应用，这些应用需要以前不可能的NO剂量。在这个项目中，研究人员将探索催化剂的结构如何影响其与各种S-亚硝基硫醇（RSNOs）的反应性，以在聚合物界面局部产生NO。此外，其他重要因素，如聚合物基质和加工方法将进行评估，以微调在表面产生的NO的剂量。该项目预计将产生治疗添加剂的新方法，并对这些材料如何作为生物有用的催化剂发挥作用有更好的基本理解。在这样做时，这项工作以以前没有使用的方式利用MOF催化剂。因此，这项工作不仅推进了生物材料领域，而且也是金属有机框架催化领域。该项目的更广泛的影响重点是在生物材料领域的学生的发展和培训，让他们接触到广泛的观点和方法，使他们准备在各种环境中工作，当他们从大学毕业。这包括学生能够独立或在合作研究团队中工作，并了解他们的专业知识如何有助于项目的整体成功。此外，非科学专业的生物材料模块将被开发和实施到本科实验室课程，以提高学生对生物材料的认识。正在开发的课程模块将明确关注与生物材料，它们的发现以及材料如何用于生物医学应用有关的问题。为了了解这个新模块的有效性，将使用前后调查来评估学生的人口统计数据，学生的动机，学生对科学的性质的看法，以及学生的学习能力。