A Bilayer Bioelectronic Implant with Piezoelectric‐Driven Immunomodulation and Bioactive Whitlockite for Bone Regeneration

ABSTRACT The loss of endogenous electrical signals after bone injury, coupled with infection and oxidative stress, often impedes natural healing. Here, we develop a bilayered scaffold integrating a piezoelectric nanofibrous membrane with a conductive antioxidative hydrogel for coordinated antibacterial defense, immunomodulation, and bone regeneration. The top layer comprises electrospun P(VDF‐TrFE) doped with polarized whitlockite (PPW), generating local electrical potentials under mechanical or mild ultrasonic stimulation. The bottom layer consists of lignin‐stabilized silver nanoparticles embedded in a polyacrylamide network (ALP), providing broad‐spectrum antibacterial activity and ROS‐scavenging in vitro. In vitro, the piezoelectric signals enhanced ALP activity and collagen I expression by 1.35‐fold, while the ALP hydrogel drove macrophage polarization from M1 toward M2. In a rat bilateral 3‐mm full‐thickness calvarial defect model, the ultrasound‐stimulated scaffold increased bone volume fraction 2.3‐fold, improved new bone formation and partial cortical bridging, and nearly doubled VEGF expression at 4 weeks relative to the ALP hydrogel group, though residual defects remained at 8 weeks. Concurrently, the scaffold upregulated TGF‐β and Runx2 while markedly suppressing TNF‐α, indicating an accelerated transition from inflammation to repair. These results demonstrate a synergistic strategy in which piezoelectric stimulation and biochemical protection jointly orchestrate osteogenesis, angiogenesis, and immunomodulation for bone tissue engineering.