Biophysical-driven piezoelectric and aligned nanofibrous scaffold promotes bone regeneration by re-establishing physiological electrical microenvironment

The initial healing stages of bone fracture is a complex physiological process involving a series of spatially and temporally overlapping events, including pathogen clearance, immunological modulation, and osteogenesis. In this study, we have developed a piezoelectric and aligned nanofibrous scaffold composed of ZnO@PCL/PVDF with multiple antibacterial, immunomodulatory, and osteogenic effects using electrospinning technology. This scaffold’s piezoelectric signal output under ultrasound (US) control can be similar to the physiological electrical signals of healthy bone tissue, creating a truly biomimetic electrical microenvironment in the bone defect. In vitro studies have shown that ZnO@PCL/PVDF scaffold significantly enhances the proliferation, migration, and osteogenic differentiation of MC3T3-E1 cells under piezoelectric drive provided by ultrasound. Furthermore, the scaffold exhibits inhibitory effects on the growth of E. coli and S. aureus, as well as the ability to induce M2 macrophage polarization, indicating potent antibacterial and immunomodulatory properties. In vivo experiments demonstrated that the ZnO@PCL/PVDF scaffold can accelerate the repair of mandibular defects in rats, effectively inhibit bacterial colonization, and reduce inflammatory responses. Altogether, this study confirms that the newly developed ZnO@PCL/PVDF scaffold effectively promotes bone repair by truly mimicking the endogenous electrical microenvironment and precisely regulating the temporospatial disorders of initial bone healing, thus providing a simple and effective solution for bone defects.