The impact of carbon based materials on hippocampal cells: from neurons to networks.

Tissue engineering and regenerative medicine require the constant development of synthetic materials to manufacture scaffolds thatbetter integrate into the target tissues (O’Brien, 2011; Ku et al, 2013; Harrison et al, 2014). In this framework, newly synthesized nanomaterials made of pure carbon, in particular Carbon Nanotubes (Ijima, 1991) and Graphene (Novoselov et al, 2004) applications to biology received particular attention due to their outstanding physicochemical properties (Hirsch, 2010). Our team has performed pioneer works during the last decade, about the interactions of neural cells with carbon nanotubes (Lovat et al, 2005; Mazzatenta et al, 2007; Cellot et al, 2009; Cellot et al, 2011; Fabbro et al, 2012; Bosi et al, 2015), and with graphene (Fabbro et al, 2015; Rauti et al, 2016) or, more in general, with synthetic substrates (Cellot et al, 2016). The major aim of my work has been to use traditional and novel physiology tools to investigate further these “neuro-hybrid systems”, and to understand how far Carbon Nanotubes and Graphene can be pushed in neuroscience applications. With this aim, in the first part of my PhD I further elucidated the behavior of newly formed synapses in primary dissociated neurons when interfaced to bi-dimensional substrates of Multi-walled Carbon Nanotubes. I then addressed the homeostasis of invitro neural networks interfaced to pure graphene and I characterized for the first time the changes induced by this material in neurons. As last step, I set up a more complex biological in-vitro model, consisting of lesioned organotypic Entorhinal-Hippocampal cultures (Perederiy and Westbrook, 2013) and we described the regenerative features of Carbon Nanotubes in this lesion model. During my PhD I was also involved in two side projects: in the first one, in collaboration with Sebastian Reinhartz and Matthew Diamond (SISSA), we refine the possible approaches of the optogenetic technique, by manipulating neuronal responses with different light waveforms (Reinhartz et al, MS in preparation, in the appendix). In the second one, in collaboration with the group of Manus Biggs, from the National University of Galway, Ireland, we tested the biocompatibility and addressed the neural behavior of primary neural cells interfaced with Indium Tin Oxide (ITO) substrates with different roughness, thickness and conducting profiles (Vallejo-Giraldo et al, 2017).