3D-printed piezoelectric scaffolds for bone regeneration: material design, biological functions, and translational...

Critical-sized bone defects remain a major clinical challenge because conventional scaffolds mainly provide structural support but lack the ability to actively regulate the regenerative microenvironment. Bone exhibits intrinsic electromechanical characteristics, where mechanical stimuli generate endogenous electrical cues involved in cellular regulation and tissue remodeling. Piezoelectric scaffolds provide a promising strategy to reconstruct this mechanoelectrical environment by converting mechanical deformation into localized electrical signals, while three-dimensional (3D) printing enables precise control over scaffold architecture, mechanical properties, and functional integration. This review summarizes recent advances in 3D-printed piezoelectric scaffolds for bone regeneration, focusing on material systems, additive-manufacturing strategies, design principles, biological functions, and preclinical applications. The fundamental mechanisms of piezoelectricity, bone electromechanical coupling, and cellular responses to electrical cues are first introduced. Subsequently, piezoelectric polymers, ceramics, and polymer-ceramic composites, together with representative printing techniques and scaffold optimization strategies, are systematically discussed. Emerging biological functions, including osteogenesis, angiogenesis, immunomodulation, antibacterial regulation, and bone remodeling, are critically evaluated with emphasis on distinguishing piezoelectric-specific effects from contributions of bioactive components and external stimulation. Finally, current challenges regarding mechanism validation, electromechanical stability, standardized evaluation, and clinical translation are highlighted. This review provides a comprehensive perspective on the rational design and future development of 3D-printed piezoelectric scaffolds toward clinically relevant bone regeneration.