Enhancing Neural Stem Cell Stimulation with Structured Piezoelectric Composites: An In Vitro Study

Abstract

Spinal cord injuries can cause permanent tissue damage with debilitating and lasting effects on patients. Electrical stimulation has been established as an effective approach for promoting neural regeneration. However, the clinical applicability of these techniques is limited by the necessity for invasive wired connections and external power supplies, which increases risk of infection. As a solution, piezoelectric materials have the inherent ability to form electric surface potentials when subjected to a mechanical load and can therefore provide wireless electrical stimulation. Recent studies have shown the potential for interfacing piezoelectric scaffolds with neural cells. However, current materials are not optimised for neurological applications as they are mechanically mis‐matched with neural tissue, have low piezoelectric properties and have poor biocompatibility. Further, reproducible systems for optimising material design and stimulation paradigms have yet to be established. In this study we demonstrate the proof‐of‐concept of a new, advanced fabrication process to produce scalable, tuneable piezoelectric chips for bench‐top testing with neural cells. We therefore provide here the first demonstration of the manufacture and characterisation of piezoelectric ceramic‐polymer composites based on [K0.5Na0.5]NbO3 and polydimethylsiloxane, produced via a novel in‐situ dielectrophoretic poling technique. Further, we demonstrate these composites can be successfully utilised for growth of primary neural stem cells (NSCs), which are shown to survive, proliferate, retain stemness and differentiate into their daughter populations on the composites. Neuronal differentiation appears to be preferred on poled substrates, in comparison to glass coverslips and unpoled substrates. We show that the composites can autonomously generate electric surface potentials, which opens new possibilities to study piezoelectrically induced electrical stimulation.This article is protected by copyright. All rights reserved.