Open Challenges and Opportunities in Piezoelectricity for Tissue Regeneration.

Emerging piezoelectric biomaterials have demonstrated their huge potential in diverse medical applications, including ultrasound diagnosis and tissue regeneration. Human body possesses inherent piezoelectricity, producing electrical signal under endogenous load or external pressure to modulate cellular behaviors. Tissue defects caused by traumatic injury will disrupt the electrophysiological microenvironment of the injured area, resulting in unenviable self-healing. Triggered by physical activities or external stimulation, piezoelectric biomaterials exhibit a unique capability to generate electrical fields to restore the electrophysical microenvironment, reprogram cell fate and ultimately facilitate tissue repair. In this review, endogenous piezoelectric substances in the body and tissue piezoelectricity are introduced. Then, the characteristics and piezoelectricity of piezoelectric biomaterials in regenerative medicine are discussed, as well as strategies to prepare novel piezoelectric composites. Moreover, the molecular mechanisms for the piezoelectric effect on regulating tissue regeneration are systematically summarized. Recent advancements in piezoelectric biomaterials are comprehensively overviewed, including in the regeneration of bone, cartilage, skeletal muscles, tendon, skin, nerve, teeth and periodontal, myocardium, blood vessel and cornea tissues. Finally, the major challenges and future perspectives of piezoelectric biomaterials in regenerative medicine are proposed, hoping to boost the advancement in this promising scientific territory.