The use of graphene-based materials to engineer sophisticated biosensing interfaces that can adapt to the central nervous system requires a detailed understanding of how such materials behave in a biological context. Graphene's peculiar properties can cause various cellular changes, but the underlying mechanisms remain unclear. Here, we show that single-layer graphene increases neuronal firing by altering membrane-associated functions in cultured cells. Graphene tunes the distribution of extracellular ions at the interface with neurons, a key regulator of neuronal excitability. The resulting biophysical changes in the membrane include stronger potassium ion currents, with a shift in the fraction of neuronal firing phenotypes from adapting to tonically firing. By using experimental and theoretical approaches, we hypothesize that the graphene-ion interactions that are maximized when single-layer graphene is deposited on electrically insulating substrates are crucial to these effects.

Physicochemical modification of implantable electrode systems is recognized as a viable strategy to enhance tissue/electrode integration and electrode performance in situ. In this work, a bench-top electrochemical process to formulate anodized ITO films with altered roughness, thickness and conducting profiles was explored. In addition, the influence of these anodized films on SH-5YSY cell proliferation, viability and focal adhesion reinforcement indicated that anodized ITO film cytocompatibility can be altered by varying the anodization current density. Furthermore, an ITO anodized films formed with a current density of 0.4 mA cm-2 showed important primary neural cell survival and promotion of neural network activity.

During the last decades, neuroscientists have increasingly exploited a variety of artificial, de-novo synthesized materials with controlled nano-sized features. For instance, a renewed interest in the development of prostheses or neural interfaces was driven by the availability of novel nanomaterials that enabled the fabrication of implantable bioelectronics interfaces with reduced side effects and increased integration with the target biological tissue. The peculiar physical-chemical properties of nanomaterials have also contributed to the engineering of novel imaging devices toward sophisticated experimental settings, to smart fabricated scaffolds and microelectrodes, or other tools ultimately aimed at a better understanding of neural tissue functions. In this review, we focus on nanomaterials and specifically on carbon-based nanomaterials, such as carbon nanotubes (CNTs) and graphene. While these materials raise potential safety concerns, they represent a tremendous technological opportunity for the restoration of neuronal functions. We then describe nanotools such as nanowires and nano-modified MEA for high-performance electrophysiological recording and stimulation of neuronal electrical activity. We finally focus on the fabrication of three-dimensional synthetic nanostructures, used as substrates to interface biological cells and tissues in vitro and in vivo.

Carbon nanotube-based biomaterials critically contribute to the design of many prosthetic devices, with a particular impact in the development of bioelectronics components for novel neural interfaces. These nanomaterials combine excellent physical and chemical properties with peculiar nanostructured topography, thought to be crucial to their integration with neural tissue as long-term implants. The junction between carbon nanotubes and neural tissue can be particularly worthy of scientific attention and has been reported to significantly impact synapse construction in cultured neuronal networks. In this framework, the interaction of 2D carbon nanotube platforms with biological membranes is of paramount importance. Here we study carbon nanotube ability to interfere with lipid membrane structure and dynamics in cultured hippocampal neurons. While excluding that carbon nanotubes alter the homeostasis of neuronal membrane lipids, in particular cholesterol, we document in aged cultures an unprecedented functional integration between carbon nanotubes and the physiological maturation of the synaptic circuits.

Highlights d Two-thirds of principal cells in the hippocampal CA1 region express slow AMPA receptors d Slow AMPA receptors show reduced desensitization and stay active for up to half a second d Increased charge transfer allows single stimulations to trigger action potentials d Postsynaptic short-term potentiation has implications for computation and cognition