Abstract

Titanium oxide nanotube arrays are extremely promising materials for localized drug delivery in orthopaedic implants because of their excellent properties and facile preparation. TiO2 nanotubes act as an effective drug reservoir for localized drug delivery and promote faster tissue regeneration, effective osseointegration while, at the same time, preventing bacterial adhesion and implant infection. Here, highly ordered TiO2 nanotubes (NTs) were synthesized by electrochemical anodization of Ti sheets and the process voltage was varied to obtain surfaces with different NTs diameters. The effect of NTs dimension on cell and bacterial adhesion and on gentamicin loading and release was assessed. Anodization was confirmed an easy and effective method to prepare highly ordered, open top nanotubes with predictable diameter as a function of imposed voltage. A lower number of bacteria Staphylococcus Aureus adhesion was found to be reduced on NTs surfaces and on smaller nanotubes in particular. When gentamicin was loaded, protracted release and antibacterial action was observed and bacteria were not observed, either in planktonic or adhered. Moreover, higher cell proliferation and a more favourable cell morphology were observed on smaller nanotubes, to further support the indication toward a reduction in NTs diameter for the preparation of effective implant surfaces.

Highlights

  • TiO2 nanotubes were first described in the nineties as having a “columnar honeycomb-like lattice,” observed upon addition of fluoride ionic species to the electrolyte in the anodization of Ti and Ti6Al4V (Zwilling and Darque-Ceretti, 1997)

  • If the length of nanotubes is considered, a reduction in nanotube depth is observed at lower voltages

  • The protocol for NTs preparation optimized in this work appeared extremely effective

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Summary

Introduction

One of the main challenges in the orthopedic field is the development of implant surfaces that combine a fast and durable fixation with an effective limitation of bacterial adhesion, to prevent implant failure and the incidence of implant-associated osteomyelitis.Among the large variety of methods aimed at improving the interfacial properties of titanium implants (Giavaresi et al, 2008; De Nardo et al, 2012; LeGeros et al, 2016; Jäger et al, 2017; Zhao et al, 2018; Stewart et al, 2019), the generation of TiO2 nanotubes (NTs) by anodization has recently attracted considerable attention with the objective to evolve from osteoconductive to osteoinductive implant performance (Farid, 2019).TiO2 nanotubes were first described in the nineties as having a “columnar honeycomb-like lattice,” observed upon addition of fluoride ionic species to the electrolyte in the anodization of Ti and Ti6Al4V (Zwilling and Darque-Ceretti, 1997). Titania nanotubes have gained interest as bone contact surfaces mainly for two characteristic properties: a unique topography, to support early osteoblast adhesion and proliferation (Iwata et al, 2017) and the possibility to Gentamicin Loaded TiO2 Nanotubes incorporate different classes of biologically-active molecules (either with osteogenic or antimicrobic activity) (Liu et al, 2016; Tao et al, 2019; Ion et al, 2020). In vitro experiments on nanotube surfaces have shown improved cell adhesion, proliferation, and differentiation, as well as enhanced bone-forming abilities (Xia et al, 2012). In vivo experiments with screw- and disk-shaped implants have shown that nanotubes’ surfaces increase direct bone/cell contact and improve osseointegration strength compared to their blasted counterpart (Bjursten et al, 2010; Sul, 2010; Li et al, 2019)

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