Titania nanotube array supported nanoceria with redox cycling stability ameliorates oxidative stress-inhibited osteogenesis

The core catalytic property of cerium oxide nanoparticles (CeNPs) has been proposed to be due to the redox cycling capability of Ce4+/Ce3+ oxidation state. Thus far there are few reports on controlling the cycling stability of Ce4+/Ce3+ couple in biological fluids which is the most important parameter in the application of CeNPs as a regenerative nano-antioxidant. In this study, vertically aligned titania nanotube array supported CeNPs (TiNTA-CeNPs), regardless of the pre-dominant Ce oxidation state, retained the cycling capability of Ce4+/Ce3+ in H2O2-containing phosphate-buffered saline (PBS) compared with Ti supported CeNPs. This was because preferable phosphate adsorption on surface Ti3+ in TiNTA-CeNPs preserved Ce3+ active sties. Accordingly, Ce3+-rich TiNTA-CeNP1 and Ce4+-rich TiNTA-CeNP2 in PBS exhibited more sustained superoxide dismutase and catalase mimetic response, respectively. A correlation between electronic band structures of Ce-Ti mixed oxides and redox potential of reactive oxygen species (ROS) aided in interpretation of enhanced redox cycling capability and enzyme-like activities. Less Fenton-active TiNTA-CeNP2 exhibited a greater ability to protect pre-osteoblasts against ROS-induced oxidative stress in vitro. To demonstrate in vivo osteoprotective effect of TiNTA-CeNP2, a rat model of oxidative stress-related osteoporosis was established. The results indicated that TiNTA-CeNP2 held great potential for ameliorating osteogenesis in oxidative stress-related bone diseases.