Nitric Oxide-Releasing Metal-Organic Frameworks: Novel Materials for Medical Device

Despite efforts to improve the efficacy of body-contacting and implantable medical devices, the incompatibility of materials within human blood and tissue still causes serious complications in patients. Thus, systemic or regional drug therapies remain necessary (e.g., use of heparin for short-term anticoagulation applications). Most often, when these drugs are administered, they produce a systemic response in the patient. Systemic responses can mask blood chemistry problems and lead to a greatly increased possibility of complications and morbidity. Research studies examining alternative mechanisms are ongoing, but there is not yet an FDA-approved alternative material that overcomes all the problems associated with body-material interactions and systemic drug therapies. As such, in clinical practice today, all implanted devices eventually fail.

To approach the aforementioned shortcomings, it is worth considering the structure and function of the ideal blood-contacting material. Preferably this material would simultaneously inhibit multiple pathways of device complication (i.e., thrombosis, inflammation, cell proliferation and migration, restenosis as well as infection) but without causing systemic side effects of its own. Such a material strategy requires not only the identification of suitable therapeutic agent(s) with appropriate biological half-lives, but the approach also requires the material’s architecture to be fabricated and tailored specifically to the needs of the clinical application. Thus, the approach to an ideal body-contacting material requires a biomaterial that can be systematically and dramatically tailored for use in a wide variety of devices while promising the simultaneous reduction in complicating factors. Currently, no material substrates exist that can be modified in such diverse ways without significantly altering the chemical, physical, or cytotoxicity properties of the material and, in turn, rendering the material unsuitable for clinical use. A modular biomaterial that can simultaneously reduce or eliminate thrombosis, inflammation, cell proliferation, and infection, and also attenuate normal tissue growth upon exposure to physiological fluid, such as blood, is paramount to improve and advance the efficacy of medical devices.