Determining the relative importance of titania nanotubes characteristics on bone implant surface performance: A quality by design study with a fuzzy approach.

TiO2 nanotubes (TNTs) are a promising bone/dental implant surface modification strategy with enhanced bioactivity and local therapeutic functions. However, inconsistencies related to the understanding of the influence of various TNTs characteristics on Ti implant functions, and the multi-factorial inter-dependence of such characteristics, requires an in-depth Quality by Design (QbD) analysis towards optimizing TNTs-modified implants. To this end, an extensive systematic literature search was undertaken to identify the various TNTs characteristics that may influence implant performance. Subsequently, in order to facilitate a QbD analysis, an expert questionnaire survey was carried out to determine the perceived contribution of various TNTs characteristics on an implant's biological, physicochemical, and mechanical performance. To achieve this goal, the Quality Function Deployment method was employed using symmetrical triangular fuzzy numbers to translate qualitative expert opinion into meaningful quantitative information. The results show that pore diameter, inter-nanotube distance and wall thickness are the TNTs characteristics with the most influential effects on the overall implant performance. This pioneering study evaluates perceived importance of various parameters contributing to TNTs functionality, and represents a step forward in the implementation of QbD strategies towards optimizing nano-engineered Ti implants.