Workpackages DescriptionWP1 WP2 WP3 WP4 WP5 WP6 WP7 WP8 WP9 WP10 WP11
The main objectives of WP7 are to design rules for the standardization of (1) assessing nanotoxicological cell responses to TiO2 nanoparticles and nanostructured coatings on Ti-alloys and (2) measurement of the osteogenic response of cells to TiO2 nanostructured coatings on Ti-alloys.
Evaluation of any potential toxicological effect will focus on cell response to both the isolated TiO2 nanoparticles and to the TiO2 nanostructured coatings on Ti-alloys. For the former the lung and gastrointestinal tract will be considered as targets as inhalation and ingestion represent the two main routes of exposure to nanopowders. Cell damage, oxidative stress, inflammation, apoptosis and genotoxicity will be evaluated as relevant endpoints for structure-activity relationship definition. From a chemical point of view, cell-free tests dealing with generation of free radicals and oxidative potential towards phospholipids, nucleic acids, proteins and antioxidants will be performed. The screening of any potential cytotoxic effects of various parameters of the nanostructured coatings will be performed, providing a simple output of key parameters that relate to biocompatible coatings.
Evaluation of the efficacy of cell response will focus on the interactions of human mesenchymal stem cells (hMSCs) on Ti-6Al-4V substrates coated with TiO2 nanoparticles and will be studied using standard in vitro culture methods; such methods are currently being incorporated in drafts of ASTM standards. Undifferentiated hMSCs will be cultured in the absence/presence of osteogenic supplements to identify the ability of defined TiO2 nanoparticle surface characteristics to affect the differentiation of the cells to bone forming cells (osteoblasts), analysed using key markers of osteogenic differentiation.