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

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 wired connections and external power supplies, which increases risk of infection. Piezoelectric materials have the inherent ability to form electric surface potentials when subjected to a mechanical stress and can provide wireless electrical stimulation. However, current materials are not optimized for neurological applications as they are mechanically mismatched with neural tissue, and have poor biocompatibility. Further, reproducible systems for optimizing material design and stimulation paradigms have yet to be established. Here a new, advanced fabrication process to produce scalable, tuneable piezoelectric ceramic-polymer composites based on [K0.5Na0.5]NbO3 and polydimethylsiloxane is provided. It is demonstrated that these composites can be successfully utilized for the growth of neural stem cells, which are shown to survive, proliferate, retain stemness, and differentiate into their daughter populations. Neuronal differentiation appears to be preferred on poled substrates, in comparison to glass coverslips and unpoled substrates. It is shown that the composites can autonomously generate surface potentials, which opens new possibilities to study piezoelectrically induced electrical stimulation. Spinal cord injury, causing permanent tissue damage, can be devastating for patients. Electrical stimulation has a profound effect on stem cells and can improve their ability to mediate repair. Here, it is shown that piezoelectric ceramic-polymer composites can be engineered to meet the mechanical and electrical properties needed by neural stem cells to attach, proliferate, and differentiate to neurons.image & COPY; 2023 WILEY-VCH GmbH