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    Antimicrobial Nitric Oxide Releasing Compounds and Scaffolds

    Published: 01 November 2020

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    Perioperative and latent infections are leading causes for the failure of orthopedic and dental implants. Their incidence is expected to increase unless innovative antimicrobial therapies and biomaterials are developed. One approach that has attracted interest is the utilization of nitric oxide (NO)-releasing biomaterials. NO is an endogenously produced lipophilic gas. It is an essential signaling molecule in many homeostatic processes and an important immunological defense against pathogens. The antimicrobial properties of NO rely, in part, on its combination with superoxide radicals to form various reactive nitrogen species. Collectively, these radicals exert nitrosative, oxidative, and osmotic stress in prokaryotic cells. Exogenous NO effectively enhances this bacteriolytic effect. NO is an ideal elutable molecule for biomedical implants because bacteriolysis occurs at the implant's surface. To date, a number of NO-releasing compounds and scaffolds have been developed, including nitrates/nitrites, nitrosyls, S-nitrosothiols, N-diazeniumdiolates, nanoparticles, biosynthetic polymers, and liposomes. Unfortunately, their clinical application has been limited due to inadequate NO payloads, uncontrolled release, and potential mammalian cell toxicity. Silicon nitride (Si3N4), a nonoxide bioceramic, is a new NO donor and scaffold that may overcome these limitations. Si3N4 modulates the release of NO in response to changes in the biological milieu, and it has the potential for extended effectiveness against pathogens. As a structural ceramic, Si3N4 has shown antimicrobial efficacy against several orthopedic and oral bacteria, and in powder form it can be incorporated into metallic and polymer composites with similar antipathogenic properties. This review addresses antimicrobial NO-releasing compounds and scaffolds, with special emphasis on silicon nitride.


    nitric oxide, reactive nitrogen species, bacteriolysis, silicon nitride

    Author Information:

    McEntire, Bryan J.
    SINTX Technologies, Inc., Salt Lake City, UT

    Bal, B. Sonny
    SINTX Technologies, Inc., Salt Lake City, UT

    Pezzotti, Giuseppe
    Ceramic Physics Laboratory, Kyoto Institute of Technology, Kyoto,

    Dept. of Orthopedic Surgery, Tokyo Medical University, Tokyo,

    The Center for Advanced Medial Engineering and Informatics, Osaka University, Osaka,

    Dept. of Immunology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto,

    Committee/Subcommittee: F04.22

    DOI: 10.1520/STP163020190161