Carbon Nanotube Scaffolds Tune Synaptic Strength in Cultured Neural Circuits: Novel Frontiers in Nanomaterial–Tissue Interactions

Abstract

A long-term goal of tissue engineering is to exploit the ability of supporting materials to govern cell-specific behaviors. Instructive scaffolds code such information by modulating (via their physical and chemical features) the interface between cells and materials at the nanoscale. In modern neuroscience, therapeutic regenerative strategies (i.e., brain repair after damage) aim to guide and enhance the intrinsic capacity of the brain to reorganize by promoting plasticity mechanisms in a controlled fashion. Direct and specific interactions between synthetic materials and biological cell membranes may play a central role in this process. Here, we investigate the role of the material's properties alone, in carbon nanotube scaffolds, in constructing the functional building blocks of neural circuits: the synapses. Using electrophysiological recordings and rat cultured neural networks, we describe the ability of a nanoscaled material to promote the formation of synaptic contacts and to modulate their plasticity.

Carbon Nanotubes: Artificial Nanomaterials to Engineer Single Neurons and Neuronal Networks

“…In this study, we showed that culturing neurons on CNT scaffolds almost doubled the probability of finding monosynaptically connected neurons, when compared to controls, i.e., CNTs guide the build-up of more synapses than in control conditions. In the same work, we further demonstrated that the strong rise in the coupling probability was due to a massive increase in synaptic density: immunofluorescence colocalization experiments reported the morphological evidence of an increase in the number of GABAergic synaptic contacts in networks grown on CNTs layers compared to that of controls 27 ( Figure 3b). This strong boosting in neuronal network connectivity is proposed to be the major mechanism by which CNTs increase the frequency of spontaneous PSCs of cultured networks reported in the previous studies 27−29 and fosters CNTs as a powerful artificial growth support able to promote de novo formation of synapses.…”

“…30,45 The summation of CNT nanotopography and physical and chemical properties provides neurons with a great deal of information, thus suggesting that neuronal contacts to CNT scaffolds might activate multiple and complex adhesion-mediated, intracellular signaling cascades. growth supports or on control glass 27 ( Figure 3a). Action potentials were evoked in the first (presynaptic) neuron by injecting a depolarizing current pulse, while the evoked unitary postsynaptic currents (PSCs, usually GABA A receptor-mediated in these experimental conditions) 27 were recorded in the second (postsynaptic) cell.…”

Chitin and carbon nanotube composites as biocompatible scaffolds for neuron growth

“…XPS analysis confirmed an increase in oxygen species and decrease in carbon species, rendering the surfaces more hydrophilic. To add to it, such surfaces had exposed nanotubes which renders the surfaces even more rough and thus, shown to promote neural synapsis 43 . We believe that the roughness in combination with increased oxygen content after plasma treatment led to better facilitation of neural adhesion and synaptic support.…”

“…Previously, nanotube-based scaffolds have been shown to be able to lead to increased connectivity by promoting synaptogenesis via modulation of deposition of an extracellular matrix more permissive for synapse construction 50 . Carbon nanotube platforms have also been shown to support network connectivity and synaptic plasticity in mammalian cortical circuits 43 . Carbon nanotube-neuron hybrid networks have been shown to detect a boost in signal transmission with increase in frequency of synaptic events 51,52 .…”

Incorporation of Conductive Materials into Hydrogels for Tissue Engineering Applications

“…Since a metal catalyst, such as, nickel can be utilized for the growth process of CNTs, nitric acid-containing oxidants are generally refined with CNTs for biological applications, which can regulate the chemical composition of CNT surfaces by making carboxylic acid groups at the terminal CNT end. CNTs are commonly utilized in biomedical applications ( Figure 8) because of their high aspect ratio, low density, and electrical and physical properties [106][107][108][109][110][111]. Zhang et al investigated the interaction between cells and modified multi-walled carbon nanotubes (MWCNTs) for biomedical applications [112].…”