Modulating Surface Potential by Controlling the β Phase Content in Poly(vinylidene fluoridetrifluoroethylene) Membranes Enhances Bone Regeneration

Abstract Bioelectricity plays a vital role in living organisms. Although electrical stimulation is introduced in the field of bone regeneration, the concept of a dose–response relationship between surface potential and osteogenesis is not thoroughly studied. To optimize the osteogenic properties of different surface potentials, a flexible piezoelectric membrane, poly(vinylidene fluoridetrifluoroethylene) [P(VDF‐TrFE)], is fabricated by annealing treatment to control its β phases. The surface potential and piezoelectric coefficients ( d 33 ) of the membranes can be regulated by increasing β phase contents. Compared with d 33 = 20 pC N −1 (surface potential = −78 mV) and unpolarized membranes, bone marrow mesenchymal stem cells (BM‐MSCs) cultured on the d 33 = 10 pC N −1 (surface potential = −53 mV) membranes have better osteogenic properties. In vivo, d 33 = 10 pC N −1 membranes result in rapid bone regeneration and complete mature bone‐structure formation. BM‐MSCs on d 33 = 10 pC N −1 membranes have the lowest reactive oxygen species level and the highest mitochondrial membrane electric potential, implying that these membranes provide the best electrical qunantity for BM‐MSCs’ proliferation and energy metabolism. This study establishes an effective method to control the surface potential of P(VDF‐Trfe) membranes and highlights the importance of optimized electrical stimulation in bone regeneration.