Ultrasound-responsive polydopamine-functionalized piezoelectric membranes for vascularized bone regeneration

Repairing bone defects presents a persistent clinical challenge that requires the coordinated promotion of antibacterial activity, vascularization, and osteogenesis. Herein, a biofunctionalized ultrasound-responsive piezoelectric scaffold (PZI) was fabricated by electrospinning ZnO/polycaprolactone (PCL) nanofibers, followed by polydopamine-mediated immobilization of icariin. Upon low-intensity pulsed ultrasound stimulation (LIPUS), the piezoelectric PZI membrane generated localized electromechanical cues that synergized with sustained biochemical signals to regulate cell-material interactions. The PZI membrane enhanced the osteogenic differentiation of bone marrow mesenchymal stromal cells (BMSCs) and promoted angiogenic behaviors of human umbilical vein endothelial cells (HUVECs), while displaying remarkable in vitro antibacterial activity against Escherichia coli and Staphylococcus aureus. Transcriptomic analysis suggested the enhanced osteogenic activities may be associated with the downregulation of the Notch signaling pathway. In a rat calvarial defect model, LIPUS-stimulated PZI scaffolds substantially accelerated new bone formation and neovascularization. Overall, this study presents a multifunctional ultrasound-responsive piezoelectric scaffold that integrates biochemical and electromechanical cues to regulate cellular behavior, providing a promising strategy for vascularized bone regeneration.