Deciphering platinum dissolution in neural stimulation electrodes: Electrochemistry or biology?

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.

Effect of Hydrogel-based Model Fibrosis on Electrical Properties of Bioelectrodes.

Fibrous tissue encapsulation can impact the performance of bioelectrodes following implantation. For example, significant increases in electrode impedance can occur within four weeks post-implantation. A key limitation hindering the understanding of host response-mediated impedance change is the reliance on animal models or complex in vitro cell cultures for electrode testing. This study aimed to develop an in vitro acellular model that can reproduce the changes in electrical properties of bioelectrodes that occur due to host responses following implantation. Specifically, the effect of synthetic, biological, and bio-synthetic co-polymer hydrogel coatings on electrode impedance was measured. Poly(vinyl alcohol) (PVA), gelatin, and PVA-gelatin co-polymers (10 and 20 wt%) were coated onto platinum (Pt) electrodes. Polarisation and access voltage, key components of the voltage response that relate to cell adhesion and protein adsorption respectively, were measured pre and post hydrogel coating and the impedance change was calculated. Results showed that increasing the polymer concentration affects the access resistance regardless of the hydrogel chemistry but only high content gelatin hydrogels increased the polarisation resistance. The increase in total impedance was ~ 2-fold of bare Pt, similar to clinical observations. This study demonstrated that an acellular fibrosis model using hydrogels could reproduce the impedance changes observed in vivo. Such a model system will support research to better understand in vivo changes in electrical properties and the longer term function of neuroprosthetic electrodes.Clinical Relevance-This study proposes an acellular fibrosis model for preclinical research. This will support the design of improved clinical stimulation strategies and better understanding of the mechanisms of impedance change at the device-tissue interface.

Bioelectronic Neural Interfaces: Improving Neuromodulation Through Organic Conductive Coatings.

Integration of bioelectronic devices in clinical practice is expanding rapidly, focusing on conditions ranging from sensory to neurological and mental health disorders. While platinum (Pt) electrodes in neuromodulation devices such as cochlear implants and deep brain stimulators have shown promising results, challenges still affect their long-term performance. Key among these are electrode and device longevity in vivo, and formation of encapsulating fibrous tissue. To overcome these challenges, organic conductors with unique chemical and physical properties are being explored. They hold great promise as coatings for neural interfaces, offering more rapid regulatory pathways and clinical implementation than standalone bioelectronics. This study provides a comprehensive review of the potential benefits of organic coatings in neuromodulation electrodes and the challenges that limit their effective integration into existing devices. It discusses issues related to metallic electrode use and introduces physical, electrical, and biological properties of organic coatings applied in neuromodulation. Furthermore, previously reported challenges related to organic coating stability, durability, manufacturing, and biocompatibility are thoroughly reviewed and proposed coating adhesion mechanisms are summarized. Understanding organic coating properties, modifications, and current challenges of organic coatings in clinical and industrial settings is expected to provide valuable insights for their future development and integration into organic bioelectronics.

Improving Deep Brain Stimulation Electrode Performance in vivo Through Use of Conductive Hydrogel Coatings.

Active implantable neurological devices like deep brain stimulators have been used over the past few decades to treat movement disorders such as those in people with Parkinson's disease and more recently, in psychiatric conditions like obsessive compulsive disorder. Electrode-tissue interfaces that support safe and effective targeting of specific brain regions are critical to success of these devices. Development of directional electrodes that activate smaller volumes of brain tissue requires electrodes to operate safely with higher charge densities. Coatings such as conductive hydrogels (CHs) provide lower impedances and higher charge injection limits (CILs) than standard platinum electrodes and support safer application of smaller electrode sizes. The aim of this study was to examine the chronic in vivo performance of a new low swelling CH coating that supports higher safe charge densities than traditional platinum electrodes. A range of hydrogel blends were engineered and their swelling and electrical performance compared. Electrochemical performance and stability of high and low swelling formulations were compared during insertion into a model brain in vitro and the formulation with lower swelling characteristics was chosen for the in vivo study. CH-coated or uncoated Pt electrode arrays were implanted into the brains of 14 rats, and their electrochemical performance was tested weekly for 8 weeks. Tissue response and neural survival was assessed histologically following electrode array removal. CH coating resulted in significantly lower voltage transient impedance, higher CIL, lower electrochemical impedance spectroscopy, and higher charge storage capacity compared to uncoated Pt electrodes in vivo, and this advantage was maintained over the 8-week implantation. There was no significant difference in evoked potential thresholds, signal-to-noise ratio, tissue response or neural survival between CH-coated and uncoated Pt groups. The significant electrochemical advantage and stability of CH coating in the brain supports the suitability of this coating technology for future development of smaller, higher fidelity electrode arrays with higher charge density requirement.

Secondary metabolites from the roots of Phlomis umbrosa.

The phytochemical study of the roots of Phlomis umbrosa Turcz afforded a new phenylethanoid glycoside, 3-hydroxy-4-methoxy-ß-phenylethoxy-O-[2,3-diacetyl-α-l-rhamnopyranosyl-(1 â†’ 3)]-4-O-cis-feruloyl-[ß-d-apiofuranosyl-(1 â†’ 6)]-ß-d-glucopyranoside (1), and two new 28-noroleanane-derived spirocyclic triterpenoids, phlomishexaol C (2) and phlomishexaol D (3). Their structures were elucidated on the basis of 1D and 2D NMR analyses, in combination with high-resolution MS experiment.