{
    "abstract": "Platinum (Pt) is the metal of choice for electrodes in implantable neural prostheses like the cochlear implants, deep brain stimulating devices, and brain-computer interfacing technologies. However, it is well known since the 1970s that Pt dissolution occurs with electrical stimulation. More recent clinical and in vivo studies have shown signs of corrosion in explanted electrode arrays and the presence of Pt-containing particulates in tissue samples. The process of degradation and release of metallic ions and particles can significantly impact on device performance. Moreover, the effects of Pt dissolution products on tissue health and function are still largely unknown. This is due to the highly complex chemistry underlying the dissolution process and the difficulty in decoupling electrical and chemical effects on biological responses. Understanding the mechanisms and effects of Pt dissolution proves challenging as the dissolution process can be influenced by electrical, chemical, physical, and biological factors, all of them highly variable between experimental settings. By evaluating comprehensive findings on Pt dissolution mechanisms reported in the fuel cell field, this review presents a critical analysis of the possible mechanisms that drive Pt dissolution in neural stimulation in vitro and in vivo. Stimulation parameters, such as aggregate charge, charge density, and electrochemical potential can all impact the levels of dissolved Pt. However, chemical factors such as electrolyte types, dissolved gases, and pH can all influence dissolution, confounding the findings of in vitro studies with multiple variables. Biological factors, such as proteins, have been documented to exhibit a mitigating effect on the dissolution process. Other biological factors like cells and fibro-proliferative responses, such as fibrosis and gliosis, impact on electrode properties and are suspected to impact on Pt dissolution. However, the relationship between electrical properties of stimulating electrodes and Pt dissolution remains contentious. Host responses to Pt degradation products are also controversial due to the unknown chemistry of Pt compounds formed and the lack of understanding of Pt distribution in clinical scenarios. The cytotoxicity of Pt produced via electrical stimulation appears similar to Pt-based compounds, including hexachloroplatinates and chemotherapeutic agents like cisplatin. While the levels of Pt produced under clinical and acute stimulation regimes were typically an order of magnitude lower than toxic concentrations observed in vitro, further research is needed to accurately assess the mass balance and type of Pt produced during long-term stimulation and its impact on tissue response. Finally, approaches to mitigating the dissolution process are reviewed. A wide variety of approaches, including stimulation strategies, coating electrode materials, and surface modification techniques to avoid excess charge during stimulation and minimise tissue response, may ultimately support long-term and safe operation of neural stimulating devices.",
    "authors": [
        {
            "affiliation": "Graduate School of Biomedical Engineering, University of New South Wales, Sydney, Australia.",
            "firstname": "Dhyey Devashish",
            "initials": "DD",
            "lastname": "Shah"
        },
        {
            "affiliation": "Cochlear Ltd, Macquarie University, NSW, Australia.",
            "firstname": "Paul",
            "initials": "P",
            "lastname": "Carter"
        },
        {
            "affiliation": "Graduate School of Biomedical Engineering, University of New South Wales, Sydney, Australia.",
            "firstname": "Mohit Naresh",
            "initials": "MN",
            "lastname": "Shivdasani"
        },
        {
            "affiliation": "Cochlear Ltd, Macquarie University, NSW, Australia.",
            "firstname": "Nicole",
            "initials": "N",
            "lastname": "Fong"
        },
        {
            "affiliation": "Graduate School of Biomedical Engineering, University of New South Wales, Sydney, Australia.",
            "firstname": "Wenlu",
            "initials": "W",
            "lastname": "Duan"
        },
        {
            "affiliation": "Graduate School of Biomedical Engineering, University of New South Wales, Sydney, Australia.",
            "firstname": "Dorna",
            "initials": "D",
            "lastname": "Esrafilzadeh"
        },
        {
            "affiliation": "Graduate School of Biomedical Engineering, University of New South Wales, Sydney, Australia; The Tyree Foundation Institute of Health Engineering, University of New South Wales, Sydney, Australia. Electronic address: l.poolewarren@unsw.edu.au.",
            "firstname": "Laura Anne",
            "initials": "LA",
            "lastname": "Poole-Warren"
        },
        {
            "affiliation": "Graduate School of Biomedical Engineering, University of New South Wales, Sydney, Australia. Electronic address: u.areguetarobles@unsw.edu.au.",
            "firstname": "Ulises Alejandro",
            "initials": "UA",
            "lastname": "Aregueta Robles"
        }
    ],
    "conclusions": null,
    "copyrights": "Copyright \u00a9 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.",
    "doi": "10.1016/j.biomaterials.2024.122575",
    "journal": "Biomaterials",
    "keywords": [
        "Biological factors",
        "Cytotoxicity",
        "Dissolution mechanisms",
        "Electrochemical factors",
        "Neural stimulating electrodes",
        "Platinum degradation products"
    ],
    "methods": null,
    "publication_date": "2024-04-28",
    "pubmed_id": "38677220",
    "results": null,
    "title": "Deciphering platinum dissolution in neural stimulation electrodes: Electrochemistry or biology?",
    "xml": "<Element 'PubmedArticle' at 0x788503fafb50>"
}