Biomimetic piezoelectric nanocomposite membranes synergistically enhance osteogenesis of deproteinized bovine bone grafts

Purpose: The combination of a bone graft with a barrier membrane is the classic method for guided bone regeneration (GBR) treatment. However, the insufficient osteoinductivity of currently-available barrier membranes and the consequent limited bone regeneration often inhibit the efficacy of bone repair. In this study, we utilized the piezoelectric properties of biomaterials to enhance the osteoinductivity of barrier membranes. Methods: A flexible nanocomposite membrane mimicking the piezoelectric properties of natural bone was utilized as the barrier membrane. Its therapeutic efficacy in repairing critical-sized rabbit mandible defects in combination with xenogenic grafts of deproteinized bovine bone (DBB) was explored. The nanocomposite membranes were fabricated with a homogeneous distribution of piezoelectric BaTiO3 nanoparticles (BTO NPs) embedded within a poly(vinylidene fluoridetrifluoroethylene) (P(VDF-TrFE)) matrix. Results: The piezoelectric coefficient of the polarized nanocomposite membranes was close to that of human bone. The piezoelectric coefficient of the polarized nanocomposite membranes was highly stable, with more than 90% of the original piezoelectric coefficient (d33) remaining up to 28 days after immersion in culture medium. Compared with commercially-available polytetrafluoroethylene (PTFE) membranes, the polarized BTO/P(VDF-TrFE) nanocomposite membranes exhibited higher osteoinductivity (assessed by immunofluorescence staining for runt-related transcription factor 2 (RUNX-2) expression) and induced significantly earlier neovascularization and complete mature bone-structure formation within the rabbit mandible critical-sized defects after implantation with DBB Bio-Oss® granules. Conclusion: Our findings thus demonstrated that the piezoelectric BTO/P(VDF-TrFE) nanocomposite membranes might be suitable for enhancing the clinical efficacy of GBR.