Piezoelectric Materials in Bone Organoids.

Abstract

Natural bone is an intrinsically piezoelectric and mechanosensitive tissue that converts mechanical stimuli into bioelectrical signals regulating bone development and regeneration. However, most existing in vitro bone models fail to recapitulate this electromechanical behavior, as current studies have largely focused on piezoelectric materials for bone repair rather than mechanical stress transmission and its piezoelectric regulation during bone development. Bone organoids have emerged as advanced three-dimensional models provides an opportunity to address this limitation, yet the electromechanical dimension of bone organoid engineering has not been systematically examined. This review advances the central argument that piezoelectric mechanosensing represents a missing but essential biophysical axis in bone organoid development. From this perspective, the piezoelectric characteristics of native bone and their roles in osteogenesis are first summarized, followed by an integrated analysis of signaling pathways activated by piezoelectric stimulation. Representative piezoelectric materials are then evaluated based on their capacity to support force-electric transduction within bone organoid systems. Finally, piezoelectric behavior-guided strategies and remaining challenges in engineering electromechanically active bone organoids are discussed. By reframing bone organoids as electromechanically regulated systems rather than purely biochemical constructs, this review provides a conceptual foundation for studying bone development under piezoelectric conditions.