Ultrasound-activated piezoelectric scaffolds target dual Ca²⁺/NF-κB signaling pathways to orchestrate immunomodulation and osteogenesis for accelerated bone regeneration.

ABSTRACT: Critical-sized bone defects fail to heal due to dysregulated inflammation and impaired osteogenesis. To overcome the limitations of static biomaterials, we engineered 3D-printed polycaprolactone scaffolds incorporating polydopamine coated BaTiO₃/β-TCP nanoparticles (10 %PBT) for dynamic ultrasound (US) activation. Integrated in vitro/in vivo analyses revealed that US-activated piezoelectricity triggered two synergistic pathways: (1) Voltage gated calcium channel (VGCC) dependent Ca²⁺ influx specifically in osteoblasts (inhibited by ω-Hexatoxin-HV1A), activating Ca²⁺/NFAT signaling and direct mineralization; and (2) Suppression of NF-κB p65 phosphorylation and nuclear translocation in macrophages, driving anti-inflammatory M2 polarization. Crucially, M2 macr

SUBMITTER: Zheng H 

PROVIDER: S-EPMC12475527 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature