Ex vivo alendronate localization at the mesoporous titania implant/bone interface.

An attractive approach in implant technology is local drug delivery, and design of efficient, safe and reliable treatments. Our hitherto strategy has been to coat Ti implants with a thin mesoporous TiO2 film that in turn is loaded with an osteoporosis drug, such as Alendronate (ALN) that is known to suppress osteoclastic activity. This system has proven highly successful and results in excellent osseointegration. However, more detailed information about drug-release and distribution at the bone/implant interface is needed. In this study, (14)C-ALN loaded titanium implants were placed up to 8 weeks into rat tibia and the spatial-temporal distribution of the drug was evaluated. Autoradiography data demonstrated a sustained release of (14)C-ALN and the released drug remained bound to bone in close vicinity, within 500 micrometers, of the implants. Liquid scintillation counting experiments confirmed that the distal transport of released (14)C-ALN was extremely low. The results are favorable as they show that ALN stays for a long time in the vicinity of the implant and may therefore improve for a long time the mechanical fixation of bone anchored implants. Moreover, these findings suggest due to the low systemic spreading a minimal risk of Alendronate related systemic side effects.

In vivo stability of hydroxyapatite nanoparticles coated on titanium implant surfaces.

PURPOSE: Nanotechnology has been employed in attempts to enhance bone incorporation of dental implants. Often, nanoparticles are applied to the implant surface as particle coatings. However, the same properties that may increase the functionality may also lead to undiscovered negative effects, such as instability of the nanocoating. The aim of this study was to investigate the stability/instability of the nanoparticles using a radiolabeling technique. MATERIALS AND METHODS: Twenty threaded and turned titanium microimplants were inserted in 10 rats. All 20 implants were coated with nanometer-sized hydroxyapatite (HA) particles. In order to trace the HA nanoparticles, the particles for 16 implants were labeled with calcium 45 (45Ca). After 1, 2, 4, and 8 weeks, the implants and surrounding bone were retrieved and analyzed using autoradiography with respect to particle migration from the implant surface. Samples from the brain, liver, thymus, kidney, and blood, as well as wooden shavings from the rats' cages, were also retrieved and analyzed using liquid scintillation counting. RESULTS: The radioactivity representing the localization of 45Ca decreased over time from the vicinity of the implant. The amounts of 45Ca found in the blood and in the rats' excretions decreased with time and corresponded well to each other. After 8 weeks, the only trace of 45Ca was found in the liver. CONCLUSION: The results indicated that released particles leave the body through the natural cleaning system, and the probability that the nanocoating will assemble in vital organs and thus become a potential biologic risk factor is unlikely.