Polymer Bioelectronics: A Solution for Both Stimulating and Recording Electrodes.

The advent of closed-loop bionics has created a demand for electrode materials that are ideal for both stimulating and recording applications. The growing complexity and diminishing size of implantable devices for neural interfaces have moved beyond what can be achieved with conventional metallic electrode materials. Polymeric electrode materials are a recent development based on polymer composites of organic conductors such as conductive polymers. These materials present exciting new opportunities in the design and fabrication of next-generation electrode arrays which can overcome the electrochemical and mechanical limitations of conventional electrode materials. This review will examine the recent developments in polymeric electrode materials, their application as stimulating and recording electrodes in bionic devices, and their impact on the development of soft, conformal, and high-density neural interfaces.

A Pilot In Vivo Study of Flexible Fully Polymeric Nerve Cuff Electrodes.

Recent trends in the field of bioelectronics have been focused on the development of electrodes that facilitate safe and efficient stimulation of nervous tissues. Novel conducting polymer (CP) based materials, such as flexible and fully polymeric conductive elastomers (CEs), constitute a promising alternative to improve on the limitations of current metallic devices. This pilot study demonstrates the performance of tripolar CE-based peripheral nerve cuffs compared to current commercial tripolar platinum-iridium (PtIr) nerve cuffs in vivo. CE and metallic cuff devices were implanted onto rodent sciatic nerves for a period of 8 weeks. Throughout the entire study, the CE device demonstrated improved charge transfer and electrochemical safety compared to the PtIr cuff, able to safely inject 2 to 3 times more charge. In comparison to the commercial control, the CE cuff was able to record in the in vivo setting with reduced noise and produced smaller voltages at all simulation levels. CE technologies provide a promising alternative to metallic devices for the development of bioelectronics with enhanced chronic device functionality.

Controlled electroactive release from solid-state conductive elastomer electrodes.

This work highlights the development of a conductive elastomer (CE) based electrophoretic platform that enables the transfer of charged molecules from a solid-state CE electrode directly to targeted tissues. Using an elastomer-based electrode containing poly (3,4-ethylenedioxythiophene) nanowires, controlled electrophoretic delivery of methylene blue (MB) and fluorescein (FLSC) was achieved with applied voltage. Electroactive release of positively charged MB and negatively charged FLSC achieved 33.19 ± 6.47 µg release of MB and 22.36 ± 3.05 µg release of FLSC, a 24 and 20-fold increase in comparison to inhibitory voltages over 1 h. Additionally, selective, and sequential release of the two oppositely charged molecules from a single CE device was demonstrated, showing the potential of this device to be used in multi-drug treatments.

Adaptive biomimicry: design of neural interfaces with enhanced biointegration.

Neural interfaces (NIs) have traditionally used inorganic device constructs paired with electrical stimulation to bypass injured or diseased electroactive tissues. These bioinert devices have significant impact on the neural tissue, being synthetic and causing large volumetric changes to the biological environment. The concept of biomimicry has become popular for tissue engineering technologies, reflecting biological properties as a component of material design. Tissue engineering strategies can be harnessed in bioelectronic device design to improve biological tolerance, but the need for improved integration with the native tissue remains an unmet need. Adaptive biomimetic designs that respond to the changing neural tissue environment associated with wound healing can actively address the immune response to improve biointegration. These adaptive approaches include responsive materials paired with stem cells and bioactive molecules as integrated components of NIs. Combining adaptive biomimetics with NIs provides a new, more natural approach for communicating with the nervous system.

Self-Assembling Hydrogel Structures for Neural Tissue Repair.

Hydrogel materials have been employed as biological scaffolds for tissue regeneration across a wide range of applications. Their versatility and biomimetic properties make them an optimal choice for treating the complex and delicate milieu of neural tissue damage. Aside from finely tailored hydrogel properties, which aim to mimic healthy physiological tissue, a minimally invasive delivery method is essential to prevent off-target and surgery-related complications. The specific class of injectable hydrogels termed self-assembling peptides (SAPs), provide an ideal combination of in situ polymerization combined with versatility for biofunctionlization, tunable physicochemical properties, and high cytocompatibility. This review identifies design criteria for neural scaffolds based upon key cellular interactions with the neural extracellular matrix (ECM), with emphasis on aspects that are reproducible in a biomaterial environment. Examples of the most recent SAPs and modification methods are presented, with a focus on biological, mechanical, and topographical cues. Furthermore, SAP electrical properties and methods to provide appropriate electrical and electrochemical cues are widely discussed, in light of the endogenous electrical activity of neural tissue as well as the clinical effectiveness of stimulation treatments. Recent applications of SAP materials in neural repair and electrical stimulation therapies are highlighted, identifying research gaps in the field of hydrogels for neural regeneration.

Mind the gap: State-of-the-art technologies and applications for EEG-based brain-computer interfaces.

Brain-computer interfaces (BCIs) provide bidirectional communication between the brain and output devices that translate user intent into function. Among the different brain imaging techniques used to operate BCIs, electroencephalography (EEG) constitutes the preferred method of choice, owing to its relative low cost, ease of use, high temporal resolution, and noninvasiveness. In recent years, significant progress in wearable technologies and computational intelligence has greatly enhanced the performance and capabilities of EEG-based BCIs (eBCIs) and propelled their migration out of the laboratory and into real-world environments. This rapid translation constitutes a paradigm shift in human-machine interaction that will deeply transform different industries in the near future, including healthcare and wellbeing, entertainment, security, education, and marketing. In this contribution, the state-of-the-art in wearable biosensing is reviewed, focusing on the development of novel electrode interfaces for long term and noninvasive EEG monitoring. Commercially available EEG platforms are surveyed, and a comparative analysis is presented based on the benefits and limitations they provide for eBCI development. Emerging applications in neuroscientific research and future trends related to the widespread implementation of eBCIs for medical and nonmedical uses are discussed. Finally, a commentary on the ethical, social, and legal concerns associated with this increasingly ubiquitous technology is provided, as well as general recommendations to address key issues related to mainstream consumer adoption.

Stretchable, Fully Polymeric Electrode Arrays for Peripheral Nerve Stimulation.

There is a critical need to transition research level flexible polymer bioelectronics toward the clinic by demonstrating both reliability in fabrication and stable device performance. Conductive elastomers (CEs) are composites of conductive polymers in elastomeric matrices that provide both flexibility and enhanced electrochemical properties compared to conventional metallic electrodes. This work focuses on the development of nerve cuff devices and the assessment of the device functionality at each development stage, from CE material to fully polymeric electrode arrays. Two device types are fabricated by laser machining of a thick and thin CE sheet variant on an insulative polydimethylsiloxane substrate and lamination into tubing to produce pre-curled cuffs. Device performance and stability following sterilization and mechanical loading are compared to a state-of-the-art stretchable metallic nerve cuff. The CE cuffs are found to be electrically and mechanically stable with improved charge transfer properties compared to the commercial cuff. All devices are applied to an ex vivo whole sciatic nerve and shown to be functional, with the CE cuffs demonstrating superior charge transfer and electrochemical safety in the biological environment.

Flexible Nanowire Conductive Elastomers for Applications in Fully Polymeric Bioelectronic Devices.

Soft, flexible polymer-based bioelectronics are a promising approach to minimize the chronic inflammatory reactions associated with metallic devices, impairing long-term device reliability and functionality. This work demonstrates the fabrication of conductive elastomers (CEs) consisting of chemically synthesized poly(3,4-ethylenedioxythiophene) (PEDOT) nanowires embedded within a polyurethane (PU) elastomeric matrix, resulting in soft and flexible, fully polymeric electrode materials. Increasing PEDOT nanowire loadings resulted in an improvement in electrochemical properties and conductivity, an increased Young's modulus and reduced strain at failure. Nanowire CEs were also found to have significantly improved electrochemical performance compared to one of the standard electrode materials, platinum (Pt). Indirect in vitro cytocompatibility test was carried out to investigate the effect of leachable substances from the CE on primary rodent cells. Nanowire CEs provide a promising alternative to metals for the fabrication of soft bioelectronics.

Conductive Hydrogel Electrodes for Delivery of Long-Term High Frequency Pulses.

Nerve block waveforms require the passage of large amounts of electrical energy at the neural interface for extended periods of time. It is desirable that such waveforms be applied chronically, consistent with the treatment of protracted immune conditions, however current metal electrode technologies are limited in their capacity to safely deliver ongoing stable blocking waveforms. Conductive hydrogel (CH) electrode coatings have been shown to improve the performance of conventional bionic devices, which use considerably lower amounts of energy than conventional metal electrodes to replace or augment sensory neuron function. In this study the application of CH materials was explored, using both a commercially available platinum iridium (PtIr) cuff electrode array and a novel low-cost stainless steel (SS) electrode array. The CH was able to significantly increase the electrochemical performance of both array types. The SS electrode coated with the CH was shown to be stable under continuous delivery of 2 mA square pulse waveforms at 40,000 Hz for 42 days. CH coatings have been shown as a beneficial electrode material compatible with long-term delivery of high current, high energy waveforms.

Conductive hydrogels: mechanically robust hybrids for use as biomaterials.

A hybrid system for producing conducting polymers within a doping hydrogel mesh is presented. These conductive hydrogels demonstrate comparable electroactivity to conventional conducting polymers without requiring the need for mobile doping ions which are typically used in literature. These hybrids have superior mechanical stability and a modulus significantly closer to neural tissue than materials which are commonly used for medical electrodes. Additionally they are shown to support the attachment and differentiation of neural like cells, with improved interaction when compared to homogeneous hydrogels. The system provides flexibility such that biologic incorporation can be tailored for application.