Neuroprosthetic technologies for therapeutic neuromodulation have seen major advances in recent years but these advances have been impeded due to electrode failure or a temporal deterioration in the device recording or electrical stimulation potential. This deterioration is attributed to an intrinsic host tissue response, namely glial scarring or gliosis, which prevents the injured neurons from sprouting, drives neurite processes away from the neuroelectrode and increases signal impedance by increasing the distance between the electrode and its target neurons. To address this problem, there is a clinical need to reduce tissue encapsulation of the electrodes in situ and improve long-term neuroelectrode function. Nanotopographical modification has emerged as a potent methodology for the disruption of protein adsorption and cellular adhesion in vitro. This study investigates the use of co-block polymer self-assembly technique for the generation of sub-20 nm nanowire features on silicon substrates. Critically, these nanostructures were observed to significantly, reduce electrical impedance and increase conductivity. Human neuroblastoma SH-SY5Y cells cultured on nanowire substrates for up to 14 days were associated with enhanced focal adhesion reinforcement and a reduction in proliferation. We conclude that nanowire surface modulation may offer significant potential as an electrode functionalization strategy