Accelerated Osteogenesis of Heterogeneous Electric Potential Gradient on CFO/P(VDF‐TrFE) Membranes

Abstract Piezoelectric biomaterials are considered to be able to mimic the electrophysiological microenvironment of natural bone tissue, thus enhancing the bone regeneration. However, the effects of heterogeneous electric potential gradient of piezoelectric biomaterials on their osteogenic performance still remain elusive, largely because of the challenge of harassing the distribution of electric potential gradient on the surface of piezoelectric biomaterials. This study controls the heterogeneous electric potential gradient on the CoFe 2 O 4 /poly(vinylidene fluoride‐trifluoroethylene (CFO/P(VDF‐TrFE)) membrane by using an alternatively positive–negative polarization processing on microscaled straight‐stripe patterned indium tin oxide coated glass (ITO) electrodes. The potential gradient (Δ ζ ) on membranes can be controlled by the stripe width and polarization parameters. Interestingly, Δ ζ shows a significant influence on the cellular osteogenic potential of mesenchymal stem cells (MSCs) and the bone regeneration performance in vivo. The Δ ζ of 0.672 pm/(V*µm) shows the optimal osteogenic performance both in vitro and in vivo, which can be attributed to the boost of integrins α 5 β 1 expression as well as the orientated arrangement and contractility of the cytoskeletons via mechanotransduction signaling cascades. This work therefore shows the importance of heterogeneous electric potential and provides a novel strategy to accelerate the osteogenic performances of piezoelectric biomaterials.