Abstract
The use of composite biomaterials as innovative bio-friendly neuronal interfaces has been poorly developed so far. Smart strategies to target neuro-pathologies are currently exploiting the mixed and complementary characteristics of composite materials to better design future neural interfaces. Here we present a polymer-based scaffold that has been rendered suitable for primary neurons by embedding graphene nanoplatelets (GnP). In particular, the growth, network formation, and functionality of primary neurons on poly(3-hydroxybutyrate) [P(3HB)] polymer supports functionalized with various concentrations of GnP were explored. After growing primary cortical neurons onto the supports for 14 days, all specimens were found to be biocompatible, revealing physiological growth and maturation of the neuronal network. When network functionality was investigated by whole patch-clamp measurements, pure P(3HB) led to changes in the action potential waveform and reduction in firing frequency, resulting in decreased neuronal excitability. However, the addition of GnP to the polymer matrix restored the electrophysiological parameters to physiological values. Interestingly, a low concentration of graphene was able to promote firing activity at a low level of injected current. The results indicate that the P(3HB)/GnP composites show great potential for electrical interfacing with primary neurons to eventually target central nervous system disorders.
Highlights
Smart neuronal interfaces are emerging as promising tools for neural tissue engineering, where scaffolds are required to provide cell support and stimulate network excitability (LizarragaValderrama et al, 2019)
Different neuronal interfaces have been developed for nerve repair/regeneration and functional recovery after neuronal injury; among these, recently, graphene-based materials have begun to be investigated due to their attractive physico-chemical properties (Akhavan, 2016; Bei et al, 2019)
Our supports displayed excellent biocompatibility, and cortical neurons were able to rapidly adhere and wire at all graphene nanoplatelets (GnP) concentrations tested in a way comparable with neurons plated on glass
Summary
Smart neuronal interfaces are emerging as promising tools for neural tissue engineering, where scaffolds are required to provide cell support and stimulate network excitability (LizarragaValderrama et al, 2019). The dynamic relation between neurons and scaffolds can be used to deliver specific stimuli to the cells in order to foster regeneration and tissue repair. Graphene has shown encouraging performances as a neuronal interfacing material because of its exceptional mechanical strength and electrical conductivity (Wick et al, 2014; Santos et al, 2021). These properties, in conjunction with its biocompatibility, have made it a good candidate with high prospects in tissue engineering, especially neural tissue engineering (Bramini et al, 2018). The electrical conductivity of graphene per se does not seem to significantly affect the adhesion and maturation of neuronal cultures (Capasso et al, 2020), graphene has been shown to interfere with the excitatory and inhibitory synaptic transmission as well as to alter Ca2+ signaling and membrane cholesterol composition (Bramini et al, 2016, 2019; Fabbro et al, 2016; Rauti et al, 2016, 2019; Chiacchiaretta et al, 2018; Durso et al, 2018; Kitko et al, 2018; Pampaloni et al, 2018)
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