Nickel doped nanohydroxyapatite: vascular endothelial growth factor inducing biomaterial for bone tissue engineering

Biomaterial induced activation of vascular endothelial growth factor (VEGF) pathway for angiogenesis is now gaining recognition as an effective option for tissue engineering. In this context, bivalent nickel (Ni2+) ion doped nano-hydroxyapatites (nHAp) were synthesized by wet chemical method, characterized and evaluated for their osteoconductive and proangiogenic properties. Electron microscopy (FESEM and TEM) along with ICP-OES analysis ensured formation of Ni2+ doped nanoparticles (average ferret diameter 15-17 nm). The 'apatite identity' of the nanoparticles was confirmed by XRD and FT-IR. Analysis revealed that Ni2+ doping caused no significant distortion in the crystal structure but decreased the crystallinity of nHAp considerably. Similarly, no major variation in the surface area (BET analysis), the zeta potential and the protein adsorption was observed among the samples. Biological characterization showed that Ni2+ doping influenced the cell viability, proliferation and differentiation of bone cells (MG-63) in a concentration dependent way. ELISA and RT-PCR study revealed that Ni2+ doped nHAp induced cellular VEGF expression many fold in comparison to control. Profiling of hypoxia inducible factor 1 alpha (HIF-1 alpha ) expression by immuno-cytochemistry and RT-PCR implied its involvement in cellular VEGF production. In conclusion, Ni2+ doped nHAp may serve as proangiogenic-osteogenic biomaterial for bone tissue engineering.