Abstract
Peripheral nerve injuries often result in nerve damage that significantly compromises functional recovery. Current treatments have substantial limitations. Engineered nerve guidance conduits emerge as a promising alternative, but their efficacy is limited when bridging large gap injuries. Schwann cells, which are essential for nerve regeneration, require a supportive microenvironment to maintain their regenerative function. Recent advances in tissue engineering focus on combining functional biomaterials and external stimuli, such as electrical stimulation, to achieve nerve guidance conduits that enhance regeneration. This study presents a piezoelectric chitosan scaffold loaded with barium titanate nanoparticles, designed for wireless electrical stimulation of Schwann cells through low-intensity pulsed ultrasound. The scaffold is engineered with an anisotropic pore microstructure to provide biomimicry. Morphological and mechanical characterization confirms that the scaffold exhibits structural properties similar to those of native neural tissue. Using a highly controlled in vitro ultrasound system, we optimize stimulation parameters to maximize cell migration and evaluate neurotrophic factor production. Gene expression analyses reveal the upregulation of cell motility and regeneration pathways. These findings demonstrate that ultrasound-activated chitosan scaffolds hold significant potential as a noninvasive tool for improving nerve regeneration, offering a comprehensive in vitro analysis to facilitate future preclinical and clinical translation.