Stimuli-Responsive Piezoelectric Scaffold as an Advanced In Vitro Platform to Drive Neural Tissue Regeneration

Developing physiologically relevant in vitro models of the human central nervous system (CNS) remains a significant challenge for neuroscience and translational research. Traditional 2D cultures and animal models often fail to capture the structural, biochemical, and functional complexity of neural tissues, limiting their predictive value for disease modeling and therapeutic testing. Here, we present stimuli-responsive piezoelectric scaffolds as advanced in vitro platforms for neural systems. Composed of egg-white proteins and piezoelectric ceramic particles (barium titanate), these scaffolds combine mechanical and structural features of the central nervous system extracellular matrix with autonomous electrical cue generation through mechanical stimulation. Physicochemical characterization demonstrated tunable porosity, mechanical strength, and controlled degradation, while biological evaluation using SH-SY5Y neural cells showed high viability, proliferation, and differentiation. Preliminary assessments suggest that scaffold polarization could play a role in enabling localized bioelectric modulation through remotely applied ultrasound that deforms the piezoelectric particles. By integrating structural and electrical responsiveness, these scaffolds may represent a versatile platform for investigating cell–cell and cell-matrix interactions, mechanotransduction, and bioelectric phenomena in CNS in vitro models, potentially offering a scalable and physiologically relevant tool for disease modeling and neuroengineering applications.