The treatment of disorders of the nervous system poses a major clinical challenge. Development of neuromodulation (i.e., interfacing electronics to nervous tissue to modulate its function) has provided patients with neuronal-related deficits a new tool to regain lost function. Even though, in principle, electrical stimulation and recording by interfacing technology is simple and straightforward, each presents different challenges. In stimulation, the challenge lies in targeting the effects of stimulation on precise brain regions, as each region specializes for particular functions on a millimeter scale. In practice, our experience with deep brain stimulation for treating Parkinson’s disease reveals that stimulation of larger regions of the brain can be relatively well tolerated. However, the task of fabricating an ideal electrode that performs reliably for long periods of time has been daunting. The primary obstacle in successful interfacing comes from integration of electrodes (“foreign” material) into the nervous system (biological material). The second tier of complexity is added by the need for the electrodes to “sense” signals emanating from individual neurons, an estimated microenvironment of 10 to 20 microns in diameter. Materials design and technology impact electrode design—with their size, shape, mechanical properties, and composition all being actively optimized to enable chronic, stable recordings of neural activity. The articles in this issue discuss designing interfacing technology to “listen to the nervous system” from a materials perspective. These include identification of materials with a potential for in vivo development, electrodes with various material types, including natural nanocomposites, and optical neural interfacing.

As biological science advances, there is a need for new technical tools to study biological matters. In neuroscience, new knowledge on the nervous system is discovered through biological experiments carried out under in vitro conditions. As experiments become more delicate, the technical requirements also increase. Recent advances in nano- and microscale technologies have increased the applicability of new emerging technology to neurobiology and neural engineering. As a result, many materials that were not originally developed for neural interfaces have become attractive candidates to sense neural signals, stimulate neurons, and grow nerve cells for tissue engineering. This article focuses on the material requirements for in vitro neural interfaces and introduces materials that are used to design various neural interface platforms in vitro.

Multi-fingered prosthetic limbs are now capable of performing complex movements, closely simulating those of the lost human arm/hand in amputees. Conveying natural control and perception of such sophisticated robotic limbs requires direct interfacing with the nervous system of the users. Both the brain and transected peripheral nerves have been proposed as appropriate locations for such neural interfaces. In the peripheral nerves, several electrode designs have been used successfully to record motor signals, and through stimulation, used to convey sensation in long-term amputee human volunteers. Here we review the advantages and limitations of peripheral nerve interfaces (PNIs) in relation to the desired characteristics for safety and performance. We compare current PNI electrodes and materials designed to increase recording sensitivity and to achieve selective stimulation of different nerves such as those carrying mechanical sensation and limb position information. Emphasis is placed on novel electrode materials, including biological coatings, conductive polymers, and nanostructured modifications. Successful development of reliable PNIs will not only enable natural control and feel of future robotic prosthetics, but will likely be a centerpiece technology in the development of multiple bionic organs.

The recording of neural signals with microelectrodes that are implanted into the cortex of the brain is potentially useful for a range of clinical applications. However, the widespread use of such neural interfaces has so far been stifled because existing intracortical electrode systems rarely allow for consistent long-term recording of neural activity. This limitation is usually attributed to scar formation and neuron death near the surface of the implanted electrode. It has been proposed that the mechanical property mismatch between existing electrode materials and the brain tissue is a significant contributor to these events. To alleviate this problem, we utilized the architecture of the sea cucumber dermis as a blueprint to engineer a new class of mechanically adaptive materials as substrates for “smart” intracortical electrodes. We demonstrated that these originally rigid polymer nanocomposites soften considerably upon exposure to emulated physiological and in vivo conditions. The adaptive nature of these bioinspired materials makes them useful as a basis for electrodes that are sufficiently stiff to be easily implanted and subsequently soften to better match the stiffness of the brain. Initial histological evaluations suggest that mechanically adaptive neural prosthetics can more rapidly stabilize neural cell populations at the device interface than rigid systems, which bodes well for improving the functionality of intracortical devices.

Complex prosthetic limbs, the bionic eye, or brain-computer interfaces implement microelectrode arrays to connect the nervous system to an electronic device. The aim is to partly restore lost body functions or to gather bioelectrical activity from the nervous system. Microelectrode arrays are fabricated to have specific electrical and mechanical properties to match the biological requirements of the intended application. Polyimide and parylene-C are favorable polymers for substrate and insulation layers in thin-film applications. This article reviews the materials and the mechanical and electrical properties of electrode arrays. It emphasizes the often ignored but crucial influence of adhesion of the thin-film layers on the device’s longevity and reliability. Adhesion promotion techniques using layers of silicon carbide (SiC) are also discussed. Even though the main focus is on thin-film devices fabricated using traditional methods of micromachining based on lithography, an alternative to thin films, laser-patterned silicone/metal foil microelectrode arrays, is also presented. Characterization as well as application examples of these devices are also presented.

Extracellular matrix (ECM)-based materials used for neural interfaces allow for prolonged effective interaction between foreign devices and the neural cells in vivo because they mimic the natural environment. This review will highlight studies that have demonstrated how ECM-based materials can benefit neural interfacing applications as neural electrode coatings, scaffolds, and nanoparticle (NP) coatings. The performance of neural electrodes can degrade from inflammatory response as indicated by the signal obstruction between neurons and electrodes from glial scar formation during prolonged implantation. ECM materials can mitigate an inflammatory response because they are naturally biocompatible and biodegradable. Scaffolds composed from ECM-based materials have the characteristic length scale and biochemical cues that promote directional neural cell growth. ECM-based scaffolds can also be utilized as drug delivery vessels to infuse the neural tissue with neural growth factors and anti-inflammatory cytokines. The NPs currently employed for drug delivery and imaging use various ECM-based coating materials that shield them from the neural cells because many types of NPs are cytotoxic. As demonstrated by these three neural interfacing applications, ECM-based materials are very promising candidates for the development of next-generation neural regeneration and therapeutic devices.