1 Antibacterial Nanostructured Ti Coatings by 2 Magnetron Sputtering : from Laboratory Scales to 3 Industrial Reactors 4

Based on an already tested laboratory procedure, a new magnetron sputtering 20 methodology to simultaneously coat two-sides of large area implants (up to ~15 cm2) with Ti 21 nanocolumns in industrial reactors has been developed. By analyzing the required growth 22 conditions in a laboratory setup, a new geometry and methodology have been proposed and tested 23 in a semi-industrial scale reactor. A bone plate (Depuy Synthes) and a pseudo-rectangular bone 24 plate extracted from a patient have been coated following the new methodology, obtaining that 25 their osteoblast proliferation efficiency and antibacterial functionality were equivalent to the 26 coatings grown in the laboratory reactor on small areas. In particular, two kinds of experiments 27 have been performed: analysis of bacterial adhesion and biofilm formation, and 28 osteoblasts-bacteria competitive in vitro growth scenarios. In all these cases, the coatings show an 29 opposite behavior towards osteoblast and bacterial proliferation, demonstrating that the proposed 30 methodology represents a valid approach for industrial production and practical application of 31 nanostructured titanium coatings. 32