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

: 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 (d33 ) of the membranes can be regulated by increasing β phase contents. Compared with d33  = 20 pC N-1 (surface potential = -78 mV) and unpolarized membranes, bone marrow mesenchymal stem cells (BM-MSCs) cultured on the d33  = 10 pC N-1 (surface potential = -53 mV) membranes have better osteogenic properties. In vivo, d33  = 10 pC N-1 membranes result in rapid bone regeneration and complete mature bone-structure formation. BM-MSCs on d33  = 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.