Wireless electrical stimulation generated by piezoelectric nanomaterial promotes the dental pulp regeneration via regulating mitochondrial Ca2+/PKA signaling pathway

The induction of dental pulp stem cells (DPSCs) into odontogenic differentiation is a cutting-edge method of dental pulp regeneration treatment. However, it remains a challenge to develop biomaterials and therapies that can induce odontogenic differentiation. Here, we propose a wireless electrical stimulation strategy to induce DPSCs odontogenic differentiation via K0.5Na0.5NbO3 piezoelectric nanoparticles (KNN) and polarized KNN (PKNN), which can be endocytosed by DPSCs. In vitro, several odontogenic differentiation indexes were also increased in DPSCs treated with KNN and PKNN, and the increase was more obvious in the PKNN group. Intracellular wireless electrical field promoted mitochondrial calcium concentration via mitochondrial calcium unidirectional transporter (MCU), increased the production of adenosine triphosphate (ATP), and induced odontogenic differentiation through the activation of the cAMP-PKA signaling pathway. In vivo, dental pulp-like tissue was induced by electrical stimulation wirelessly with KNN and PKNN, which was more clinically friendly compared with the wired device, and the induction was more obvious in the PKNN group consistent with in vitro experiments. In conclusion, this work demonstrates the potential of PKNN as an effective stimulus that can induce odontogenic differentiation of DPSCs and be applied to dental pulp regeneration treatment.