An in vitro study of a titanium surface modified by simvastatin-loaded titania nanotubes-micelles.

To develop an optimized local delivery system of simvastatin (SV) with improved osseointegration of titanium (Ti) implants, SV-loaded poly(ethylene glycol)-poly(epsilon-caprolactone) (PECL) micelles (80 nm in diameter) were loaded in titania nanotube (TNT) arrays (80-100 nm in diameter and 400 nm in length) that were fabricated by anodizing Ti sheets. An in vitro release experiment was performed and revealed that TNTs and micelles can jointly provide a sustained release of SV, and that TNTs alone might function in drug release. The effect of the Ti surface with TNTs or TNTs-micelles on osteoblast-like MG-63 cells was determined by analyzing cell morphology, cytoskeletal arrangement, early adhesion, proliferation, alkaline phosphatase activity, and intracellular and extracellular osteocalcin content. The results indicate that the Ti surface with SV-loaded TNTs-micelles not only has better able to promote early adhesion, spreading and early differentiation of osteoblasts than the Ti surface with TNTs alone but it is able to promote calcification of osteoblasts. Therefore, a Ti surface with TNTs or TNTs-micelles is expected to promote contact osteogenesis of the Ti implant, thus contributing to early osseointegration of the implant, whereas the osteogenic effect of the Ti surface with TNTs-micelles is expected to be stronger. This local delivery system can bridge the gap between basic research and applied science for a wide range of titanium-based orthopedic implants in diverse bone-loss diseases, including osteoporosis.