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, hierar-chically 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 Zn2+ released from ZIF-8, leading to Zn2+ 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 Zn2+ 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 Zn2+, 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.