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 (ESdynamic) 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 (ESstatic) 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 ESdynamic and significantly enhanced bone integration through ESstatic-driven immunomodulation. This ferroelectric biointerface-mediated immunomodulation presents a synchronized noninvasive strategy for treating infected implants.