Piezoelectric Nanocomposite Hydrogel for Wireless Neural Stimulation and Tissue Augmentation

Wireless piezoelectric stimulation can be used for minimally invasive and targeted neuromodulation, including augmenting neural tissue induction in vitro and regeneration in vivo. Here, we describe piezoelectric nanocomposite hydrogel (PZ‐gel)‐based neural tissues comprising alginate, carboxymethyl chitosan, and barium titanate nanoparticles (BTNPs), with optimal biomechanical properties for simultaneous sonoactivation, stable human neural stem cell support, piezoelectric stimulation, and augmented neural cell and tissue induction. Hence, the PZ‐gel has viscoelastic properties and a modulus amenable to stem and derivative cell culture, and BTNP inclusion enhances its mechanical strength, elasticity, and structural stability. Activation of the PZ‐gel with ultrasound enhances stem cell differentiation to neurons with dense neuronal networks and supporting neuroglia, underscoring the ultrasound‐mediated piezoelectric effect. We submit that our PZ‐gel may be applied as a smart substrate for advanced in vitro neural tissue engineering and a resorbable injectable or mouldable electric tissue prosthesis for wireless cell/tissue stimulation and repair.