Effect of size and crystalline phase of TiO2 nanotubes on cell behaviors: A high throughput study using gradient TiO2 nanotubes

The research of TiO₂ nanotubes (TNTs) in the field of biomedicine has been increasingly active. However, given the diversity of the nanoscale dimension and controversial reports, our understanding of the structure-property relationships of TNTs is not yet complete. In this paper, gradient TNTs with a wide diameter range of 20-350 nm were achieved by bipolar electrochemistry and utilized for a thorough high-throughput study of the effect of nanotube dimension and crystalline phase on protein adsorption and cell behaviors. Results indicated that protein adsorption escalated with nanotube dimension whereas cell proliferation and differentiation are preferred on small diameter (<70 nm) nanotubes. Large diameter anatase nanotubes had higher adsorption of serum proteins than as-prepared ones. But only as-prepared small diameter nanotubes presented slightly higher cell proliferation than corresponding annealed nanotubes whereas there was no discernible difference between as-prepared and annealed nanotubes on cell differentiation for the entire gradient. Those findings replenish previous research about how cell responses to TNTs with a wide diameter range and provide scientific guidance for the optimal design of biomedical materials.