A Soft, Flexible Implant for Wireless Photothermal–Pyroelectric Neurostimulation

ABSTRACT Neural progenitor cells (NPCs) are widely recognized as promising seed cells for the treatment of neurodegenerative diseases due to their inherent potential to differentiate into functional neurons. However, due to the low differentiation efficiency, their practical application in neural repair remains a significant challenge. In this work, we present a novel, non‐invasive strategy to enhance the neuronal differentiation of NPCs through photothermal‐pyroelectric stimulation. Specifically, a hybrid film was fabricated by coating BaTiO 3 (BTO) nanocrystals – comprising either nanoparticles or nanosheets – onto the surface of a CNT@PDMS composite membrane. Under periodic light irradiation, the photothermal effect triggered rapid temperature oscillations, which activated BTO's pyroelectric effect, generating localized electric stimulation that promoted neuronal differentiation of NPCs. Immunofluorescent staining and Western blot analysis further confirmed that the observed enhancement in neural differentiation was mediated by the activation of Ca 2+ signaling and the PI3K/Akt pathway. Moreover, comparative experiments revealed that BTO nanosheets with highly exposed (001) facets exhibited markedly enhanced neurogenic differentiation capabilities relative to BTO nanoparticles, highlighting the facet‐dependent pyroelectric effect. This work presents wireless photothermal‐pyroelectric stimulation for neural differentiation and, for the first time, proposes a pyroelectric regenerative medicine for the non‐invasive repair of damaged neural tissue.