Optimizing the Electrical Microenvironment Provided by 3D Micropillar Topography on a Piezoelectric BaTiO 3 Substrate to Enhance Osseointegration

Abstract The electrical properties of bone implant scaffolds are a pivotal factor in regulating cellular behavior and promoting osteogenesis. The previous study shows that built‐in electric fields established between electropositive nanofilms and electronegative bone defect walls are beneficial for promoting bone defect healing. Considering that the physiological electrical microenvironment is spatially distributed in 3D, it is imperative to establish a 3D spatial charged microenvironment on bone scaffolds to optimize the efficacy of osseointegration. Nevertheless, this still poses a formidable challenge. Here, a bone repair strategy that utilizes micro‐scale 3D topography is developed on a piezoelectric BaTiO 3 (BTO) substrate to provide 3D spatial electrical stimulation. The BTO micropillar arrays, especially with a height of 50 µm and positive‐charge distribution (50 µm positive), promote the spreading, cytoskeletal reorganization, focal adhesion maturation, and osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs). They enhanced the clustering of mechanosensing integrin α5 in BMSCs. The biomimetic 3D spatial electrical microenvironment accelerated bone repair and osseointegration in a rat femoral diaphysis defect repair model. The study thus reveals that implants with a 3D spatial electrical microenvironment can significantly enhance osseointegration, thereby providing a new strategy to optimize the performance of electroactive biomaterials for tissue regenerative therapies.