Bioengineered hollow nanoflowers to synergistically modulate inflammation, angiogenesis and osteogenesis for enhancing repair of bone defects

Abstract Background Inadequate control of inflammation and insufficient vascularization remain major challenges in repair of bone defects. Here, we developed a multifunctional nanoflower, Au NPs@ZIF-8/Ga, by loading gallic acid (Ga) into a nanoflower-like structure consisting of gold nanoparticles (Au NPs) core and zeolitic imidazolate framework-8 (ZIF-8) shell, to synergistically exert anti-inflammatory, pro-angiogenic, and osteogenic effects. Results The hollow architectures of the synthesized Au NPs@ZIF-8/Ga nanoflowers were characterized by transmission electron microscopy (TEM), energy-dispersive spectroscopy (EDS), X-ray diffraction (XRD), Fourier-transform infrared spectroscopy (FTIR), and nitrogen adsorption–desorption analysis. In vitro studies demonstrated that Au NPs@ZIF-8/Ga reduced secretion of pro-inflammatory cytokines in macrophages via suppressing NF-κB pathway activation, while concurrently promoted endothelial cell migration, and tube formation. Yet, Au NPs@ZIF-8/Ga enhanced osteogenic differentiation of MC3T3-E1 cells, as evidenced by the upregulated expression of bone formation related genes runt-related transcription factor 2 (RUNX2) and osteocalcin (OCN), as well as increased alkaline phosphatase (ALP) activity and bone matrix mineralization. In vivo studies showed that Au NPs@ZIF-8/Ga promoted early resolution of inflammation, neovascularization and robust new bone formation in a rat model with critical-sized calvarial defects, as confirmed by Micro-computed tomography (micro-CT) and histological analyses. Conclusion Collectively, this work presents a versatile nanoplatform for reducing inflammation in early stage while subsequently promoting angiogenesis and osteogenesis, thereby offering a promising therapeutic strategy for bone regeneration under inflammatory conditions. Graphical abstract