Enhanced bone regeneration via ZIF-8 decorated hierarchical polyvinylidene fluoride piezoelectric foam nanogenerator: Coupling of bioelectricity, angiogenesis, and osteogenesis

Piezoelectric biomaterials are advantageous in terms of easy generation of transduced bioelectrical signals to skeleton systems in response to body movements or external stimulations . In the bone formation process, the coupling of angiogenesis-osteogenesis is crucial but the effect of piezoelectric biomaterials on angiogenesis and mechanism of stress-transformed electrical signals affecting vascular cells remain elusive. In this work, hierarchically architected polyvinylidene fluoride (PVDF) foam fabricated by solid-state shearing milling was further decorated with ZIF-8 nanocrystals . The unique hierarchical porous structure realizes stable voltage outputs up to 10 V without polarization. The electric potential of piezoelectric PVDF affected molecular trajectory of Zn 2+ released from ZIF-8, leading to Zn 2+ enrichment around the PVDF surface. Under piezoelectric condition, PVDF/ZIF-8 foams promoted in-vitro angiogenic and osteogenic activity as well as antibacterial effect. Upon calvarium and femur defect repair, PVDF/ZIF-8 piezoelectric foams also guided vascularized bone regeneration through micro-current stimulation and Zn 2+ enrichment. RNA-seq demonstrated PVDF/ZIF-8 piezoelectric foam mainly up-regulated ATP coupled cation transmembrane transportation in vascular endothelial cells, which enhanced cellular uptake of Zn 2+ , indicating the synergistic effect of piezoelectric PVDF and bioactive ZIF-8. This work offers a preliminary explanation for mechanism of angiogenesis-osteogenesis coupling of PVDF/ZIF-8 foam nanogenerator and provides a valuable complement to clinical treatment strategies for bone defect repair.