Porous copper- and lithium-doped nano-hydroxyapatite composite scaffold promotes angiogenesis and bone regeneration in the repair of glucocorticoids-induced osteonecrosis of the femoral head

Abstract

Glucocorticoids-induced osteonecrosis of the femoral head (GIONFH) is a common refractory disease. In the present study, we aimed to synthesize the nano-hydroxyapatite-copper-lithium (Cu-Li-nHA) composite porous scaffold to promote osteogenesis and angiogenesis functions to repair GIONFH by regulating the Wnt/<i>β</i>-catenin and HIF-1<i>α</i>/VEGF pathways. The physicochemical property of the scaffold was characterized and their osteogenic and angiogenic effects were tested through a serial of experiments<i>in vitro</i>and<i>in vivo</i>. Results showed that 0.25% Cu-Li-nHA scaffolds possessed the highest mechanical and biocompatibility<i>in vitro</i>. Then the 0.25% Cu-Li-nHA scaffolds significantly enhanced the new bone formation on defects in GIONFH rabbits<i>in vivo</i>. Moreover, the scaffold could increase the expression of osteogenic and angiogenic factors along with the activation of factors in Wnt/<i>β</i>-catenin and HIF-1<i>α</i>/VEGF pathways<i>in vitro</i>and<i>in vivo</i>. In conclusion, the 0.25% Cu-Li-nHA scaffold could improve the osteogenesis and angiogenesis by upregulating the Wnt/<i>β</i>-catenin and HIF-1<i>α</i>/VEGF pathways which benefited to repair the GIONFH in rabbit models.