Development and Characterization of PEDOT:PSS/Alginate Soft Microelectrodes for Application in Neuroprosthetics
TL;DR: The fabrication of a conductive hydrogel-based microelectrode array for neural recording using a hybrid material composed of poly(3,4-ethylenedioxythiophene)-poly(styrenesulfonate), and alginate is reported, representing an advancement in the design of soft conductive electrodes for neuroprosthetic applications.
Abstract: Reducing the mechanical mismatch between the stiffness of a neural implant and the softness of the neural tissue is still an open challenge in neuroprosthetics. The emergence of conductive hydrogels in the last few years has considerably widened the spectrum of possibilities to tackle this issue. Nevertheless, despite the advancements in this field, further improvements in the fabrication of conductive hydrogel-based electrodes are still required. In this work, we report the fabrication of a conductive hydrogel-based microelectrode array for neural recording using a hybrid material composed of poly(3,4-ethylenedioxythiophene)-poly(styrenesulfonate), and alginate. The mechanical properties of the conductive hydrogel have been investigated using imaging techniques, while the electrode arrays have been electrochemically characterized at each fabrication step, and successfully validated both in vitro and in vivo. The presence of the conductive hydrogel, selectively electrodeposited onto the platinum microelectrodes, allowed achieving superior electrochemical characteristics, leading to a lower electrical noise during recordings. These findings represent an advancement in the design of soft conductive electrodes for neuroprosthetic applications.
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TL;DR: A comprehensive review of the recent advances in biocompatible conductors based on natural biopolymers for stretchable bioelectronics can be found in this article, where the authors discuss the electronic component-biopolymer interface and bioelectronic-biological tissue (skin and internal tissues) interface.
Abstract: Biocompatible conductors are important components for soft and stretchable bioelectronics for digital healthcare, which have attracted extensive research efforts. Natural biopolymers, compared to other polymers, possess unique features that make them promising building blocks for biocompatible conductors, such as good biocompatibility/biodegradability, natural abundance, sustainability, and capability, can be processed into various functional formats with tunable material properties under benign conditions. In this comprehensive review, we focus on the recent advances in biocompatible conductors based on natural biopolymers for stretchable bioelectronics. We first give a brief introduction of conductive components and natural polymers and summarize the recent development of biocompatible conductors based on representative natural biopolymers including protein (silk), polypeptide (gelatin), and polysaccharide (alginate). The design and fabrication strategies for biocompatible conductors based on these representative biopolymers are outlined, after the chemical structure and properties of such biopolymers are presented. Then we discuss the electronic component-biopolymer interface and bioelectronic-biological tissue (skin and internal tissues) interface, highlight various fabrication techniques of biocompatible conductors for soft bioelectronics, and introduce representative examples of utilizing natural biopolymer-based biocompatible conductors for on-skin bioelectronics, textile-based wearable electronics, and implantable bioelectronics for digital healthcare. Finally, we present concluding remarks on challenges and prospects for designing natural biopolymers for soft biocompatible conductors and bioelectronics.
132 citations
TL;DR: This review describes the current state of the art of in vitro, ex vivo, and in vivo models available for the study of neural tissue response to implantable microelectrodes and highlights new models with increased complexity that closely mimic in vivo scenarios.
Abstract: The development of implantable neuroelectrodes is advancing rapidly as these tools are becoming increasingly ubiquitous in clinical practice, especially for the treatment of traumatic and neurodegenerative disorders. Electrodes have been exploited in a wide number of neural interface devices, such as deep brain stimulation, which is one of the most successful therapies with proven efficacy in the treatment of diseases like Parkinson or epilepsy. However, one of the main caveats related to the clinical application of electrodes is the nervous tissue response at the injury site, characterized by a cascade of inflammatory events, which culminate in chronic inflammation, and, in turn, result in the failure of the implant over extended periods of time. To overcome current limitations of the most widespread macroelectrode based systems, new design strategies and the development of innovative materials with superior biocompatibility characteristics are currently being investigated. This review describes the current state of the art of in vitro, ex vivo, and in vivo models available for the study of neural tissue response to implantable microelectrodes. We particularly highlight new models with increased complexity that closely mimic in vivo scenarios and that can serve as promising alternatives to animal studies for investigation of microelectrodes in neural tissues. Additionally, we also express our view on the impact of the progress in the field of neural tissue engineering on neural implant research.
81 citations
TL;DR: In this paper, a short review aims to provide an overview of how poly(3,4-ethylene dioxythiophene) (PEDOT) coatings have contributed to functionalizing existing bioelectronics, the challenges which meet conducting polymer coatings from a regulatory and stability point of view and the possibilities to bring PEDOT-based coatings into large-scale clinical applications.
Abstract: The widespread use of conducting polymers, especially poly(3,4-ethylene dioxythiophene) (PEDOT), within the space of bioelectronics has enabled improvements, both in terms of electrochemistry and functional versatility, of conventional metallic electrodes. This short review aims to provide an overview of how PEDOT coatings have contributed to functionalizing existing bioelectronics, the challenges which meet conducting polymer coatings from a regulatory and stability point of view and the possibilities to bring PEDOT-based coatings into large-scale clinical applications. Finally, their potential use for enabling new technologies for the field of bioelectronics as biodegradable, stretchable and slow-stimulation materials will be discussed.
58 citations
TL;DR: It is concluded that DC-based neural implants are a promising new modulation technology that could benefit from further chronic safety assessments and a better understanding of the basic biological and biophysical mechanisms that underpin DC-mediated neural modulation.
Abstract: Implantable neuroprostheses such as cochlear implants, deep brain stimulators, spinal cord stimulators, and retinal implants use charge-balanced alternating current (AC) pulses to recover delivered charge and thus mitigate toxicity from electrochemical reactions occurring at the metal-tissue interface. At low pulse rates, these short duration pulses have the effect of evoking spikes in neural tissue in a phase-locked fashion. When the therapeutic goal is to suppress neural activity, implants typically work indirectly by delivering excitation to populations of neurons that then inhibit the target neurons, or by delivering very high pulse rates that suffer from a number of undesirable side effects. Direct current (DC) neural modulation is an alternative methodology that can directly modulate extracellular membrane potential. This neuromodulation paradigm can excite or inhibit neurons in a graded fashion while maintaining their stochastic firing patterns. DC can also sensitize or desensitize neurons to input. When applied to a population of neurons, DC can modulate synaptic connectivity. Because DC delivered to metal electrodes inherently violates safe charge injection criteria, its use has not been explored for practical applicability of DC-based neural implants. Recently, several new technologies and strategies have been proposed that address this safety criteria and deliver ionic-based direct current (iDC). This, along with the increased understanding of the mechanisms behind the transcutaneous DC-based modulation of neural targets, has caused a resurgence of interest in the interaction between iDC and neural tissue both in the central and the peripheral nervous system. In this review we assess the feasibility of in-vivo iDC delivery as a form of neural modulation. We present the current understanding of DC/neural interaction. We explore the different design methodologies and technologies that attempt to safely deliver iDC to neural tissue and assess the scope of application for direct current modulation as a form of neuroprosthetic treatment in disease. Finally, we examine the safety implications of long duration iDC delivery. We conclude that DC-based neural implants are a promising new modulation technology that could benefit from further chronic safety assessments and a better understanding of the basic biological and biophysical mechanisms that underpin DC-mediated neural modulation.
32 citations
Cites background from "Development and Characterization of..."
...These coatings are collectively referred to as hydrogel polymer coatings, with PEDOT:PSS as the most well-known of these (Nyberg et al., 2002; Ferlauto et al., 2018)....
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TL;DR: In this article, representative fabrication approaches of conductive and stretchable nanocomposites for implantable soft electronics and various in vivo applications of implantablesoft electronics are focused on.
Abstract: Research on the field of implantable electronic devices that can be directly applied in the body with various functionalities is increasingly intensifying due to its great potential for various therapeutic applications. While conventional implantable electronics generally include rigid and hard conductive materials, their surrounding biological objects are soft and dynamic. The mechanical mismatch between implanted devices and biological environments induces damages in the body especially for long-term applications. Stretchable electronics with outstanding mechanical compliance with biological objects effectively improve such limitations of existing rigid implantable electronics. In this article, the recent progress of implantable soft electronics based on various conductive nanocomposites is systematically described. In particular, representative fabrication approaches of conductive and stretchable nanocomposites for implantable soft electronics and various in vivo applications of implantable soft electronics are focused on. To conclude, challenges and perspectives of current implantable soft electronics that should be considered for further advances are discussed.
27 citations
References
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TL;DR: This review will provide a comprehensive overview of general properties of alginate and its hydrogels, their biomedical applications, and suggest new perspectives for future studies with these polymers.
5,372 citations
"Development and Characterization of..." refers background in this paper
...Lastly, taking into consideration the possibility of the alginate to dissolve with time during chronic implantation (Lee and Mooney, 2012), we also verified that a protective coating of the probe with Poly(ethylene glycol) dimethacrylate (PEGDMA), created by dip-coating, would not alter the electrochemical properties of the CA-based electrodes (Figure 7)....
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TL;DR: From Wichterle’s pioneering work to the most recent hydrogel-based inventions and products on the market, it provides the reader with a detailed introduction to the topic and perspective on further potential developments.
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TL;DR: Focusing mainly on polypyrrole, polyaniline and poly(3,4-ethylenedioxythiophene), this work reviews conductive polymers from the perspective of tissue engineering.
1,347 citations
TL;DR: This article aims to review the literature concerning the choice of selectivity for hydrogels based on classification, application and processing to assess their potential in hi-tech applications in the biomedical, pharmaceutical, biotechnology, bioseparation, biosensor, agriculture, oil recovery and cosmetics fields.
905 citations
TL;DR: The NeuroGrid constitutes an effective method for large-scale, stable recording of neuronal spikes in concert with local population synaptic activity, enhancing comprehension of neural processes across spatiotemporal scales and potentially facilitating diagnosis and therapy for brain disorders.
Abstract: Recording from neural networks at the resolution of action potentials is critical for understanding how information is processed in the brain. Here, we address this challenge by developing an organic material-based, ultraconformable, biocompatible and scalable neural interface array (the 'NeuroGrid') that can record both local field potentials(LFPs) and action potentials from superficial cortical neurons without penetrating the brain surface. Spikes with features of interneurons and pyramidal cells were simultaneously acquired by multiple neighboring electrodes of the NeuroGrid, allowing for the isolation of putative single neurons in rats. Spiking activity demonstrated consistent phase modulation by ongoing brain oscillations and was stable in recordings exceeding 1 week's duration. We also recorded LFP-modulated spiking activity intraoperatively in patients undergoing epilepsy surgery. The NeuroGrid constitutes an effective method for large-scale, stable recording of neuronal spikes in concert with local population synaptic activity, enhancing comprehension of neural processes across spatiotemporal scales and potentially facilitating diagnosis and therapy for brain disorders.
712 citations
"Development and Characterization of..." refers background in this paper
...CPs and CNTs are versatile carbon-based materials already exploited in the fabrication of several neuroprosthetic devices (Antognazza et al., 2015; Khodagholy et al., 2015; Feyen et al., 2016; Xiang et al., 2016; Ferlauto et al., 2018)....
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