Piezoelectric Biomaterials for Bone Regeneration: Roadmap from Dipole to Osteogenesis.

Piezoelectric biomaterials convert mechanical energy into electrical charges, making them promising candidates for bone tissue engineering by restoring and modulating the electrophysiological microenvironment. This review explores the development of piezoelectric biomaterials by focusing on their molecular origins, particularly dipoles, and how their type, source, and spatial arrangement influence macroscopic electromechanical coupling. Beyond intrinsic origins, the concept of pseudo-piezoelectricity driven by extrinsic factors is introduced to highlight alternative approaches for piezoelectric biomaterial design. Techniques to engineer dipoles and modulate piezoelectric properties for the regulation of osteogenesis are discussed. Particular attention is given to the correlation between piezoelectricity and osteogenesis at distinct phases of bone regeneration. Finally, current challenges in molecular understanding and biofabrication of piezoelectric bone scaffolds are highlighted, along with potential future research directions.