Tailoring Piezoelectric Nanogenerators and Microdevices for Cellular Excitation: Impact of Size and Morphology

The use of piezoelectric devices as wireless electrical stimulators is an emerging research topic. In this study, piezoelectric microdevices, consisting of ZnO nanosheets (NSs) functioning as piezoelectric nanogenerators (NGs) grown on top of silicon microparticles, to electrically stimulate cell are designed. The morphology of the ZnO NSs is optimized by tuning the thickness of the aluminum nitride (AlN) catalyst layer and adjusting the growth duration. ZnO NSs grown on thinner AlN layers (≤ 200 nm) and subjected to 9 h of hydrothermal growth exhibit the most suitable characteristics for cell stimulation, balancing crystal size, and electric field generation. The generation of a local electric field capable of exciting osteoblast cells is inferred from finite element simulations and intracellular calcium influx measurements. The internalization rate of silicon microdevices of varying sizes (3 × 3, 6 × 10, 12 × 18 µm²) by osteosarcoma (Saos-2) and primary human osteoblast (hOB) cells is assessed. The results show that smaller devices have higher internalization rates, particularly in tumoral Saos-2 cells, while primary cells exhibit minimal internalization (< 10%) across all particle sizes. This study presents an optimized piezoelectric microdevice, based on a scalable and customizable fabrication process, for minimally invasive bioelectronic applications, offering accurate electrical cell stimulation while minimizing unwanted internalization.