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

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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.