Yingying Chu

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.

Infected wounds provoke persistent inflammation that hinders healing. Here, we developed a phase-adaptable, injectable hydrogel (PAC@TAP) that delivers sequential antibacterial, antioxidant, anti-inflammatory, and regenerative effects. Bioactive nanoparticles (AC@TAP) were prepared by loading Centella asiatica onto polydopamine, in situ polymerizing silver, and coating with tannic acid, then embedded in a dynamic QCS/OHA/PVA matrix. Reversible Schiff-base, ionic, and borate-ester cross-links (PVA/Ca²⁺/CPBA) endow injectability, self-healing, and strong tissue adhesion with PAC@TAP hydrogel. The composite hydrogel exhibits potent antibacterial activity, efficient ROS scavenging, and immunomodulation effects, thereby accelerating scar-minimizing healing of infected wounds. In vitro, PAC@TAP is cytocompatible and enhances cell migration. In vivo, near-infrared stimulation accelerates closure, dampens inflammation, and promotes angiogenesis. This integrated design uniquely couples antimicrobial defense with immune regulation and tissue regeneration, offering a promising strategy for advanced infected wound therapy.

Recapitulating the natural extracellular physical microenvironment has emerged as a promising method for tissue regeneration, as multiple physical interventions, including ultrasound, thermal and electrical therapy, have shown great potential. However, simultaneous coupling of multiple physical cues to highly bio-mimick natural characteristics for improved tissue regeneration still remains formidable. Coupling of intrinsic electrical and mechanical cues has been regarded as an effective way to modulate tissue repair. Nevertheless, precise and convenient manipulation on coupling of mechano-electrical signals within extracellular environment to facilitate tissue regeneration remains challengeable. Herein, a photothermal-sensitive piezoelectric membrane was designed for simultaneous integration of electrical and mechanical signals in response to NIR irradiation. The high-performance mechano-electrical coupling under NIR exposure synergistically triggered the promotion of osteogenic differentiation of stem cells and enhances bone defect regeneration by increasing cellular mechanical sensing, attachment, spreading and cytoskeleton remodeling. This study highlights the coupling of mechanical signals and electrical cues for modulation of osteogenesis, and sheds light on alternative bone tissue engineering therapies with multiple integrated physical cues for tissue repair. Graphical Abstract