Sequential bioelectric programming of Macrophages via ferroelectric nanostructured surface to combat implant infection and promote bone integration

Implant-associated infections impair osseointegration by suppressing macrophage-mediated antibacterial responses and blocking reparative phenotype transition, while conventional antimicrobial strategies may compromise bone regeneration. Although electrical stimulation holds promise for macrophage modulation, achieving spatiotemporally controlled bioelectrical regulation remains a challenge. Herein, we engineered a ferroelectric barium titanate-nanostructured titanium implant (ferroTi) that enables sequentially controlled electrical manipulation of macrophages for coordinated antibacterial action and osteogenic promotion. Under ultrasound (US) activation, ferroTi generates dynamic electrical signals (ES_dynamic) which activate voltage-gated Ca²⁺ channels to potentiate bacterial phagocytosis in macrophages, eradicating the methicillin-resistant Staphylococcus aureus (MRSA) infection. Concurrently, ferroTi's inherent surface potential provides static electrical signals (ES_static) that enhance focal adhesion of macrophages and polarize macrophages toward an anti-inflammatory phenotype to foster bone mesenchymal stem cell osteogenesis. In vivo, ferroTi successively eliminated MRSA infection via US-activated ES_dynamic and significantly enhanced bone integration through ES_static-driven immunomodulation. This ferroelectric biointerface-mediated immunomodulation presents a synchronized noninvasive strategy for treating infected implants.