Titania nanotubes (TNTs) fabricated on titanium orthopedic and dental implants have shown significant potential in "proof of concept" in vitro, ex vivo, and short-term in vivo studies. However, most studies do not focus on a clear direction for future research towards clinical translation, and there exists a knowledge gap in identifying key research challenges that must be addressed to progress to the clinical setting. This review focuses on such challenges with respect to anodized titanium implants modified with TNTs, including optimized fabrication on clinically utilized microrough surfaces, clinically relevant bioactivity assessments, and controlled/tailored local release of therapeutics. Further, long-term in vivo investigations in compromised animal models under loading conditions are needed. We also discuss and detail challenges and progress related to the mechanical stability of TNT-based implants, corrosion resistance/electrochemical stability, optimized cleaning/sterilization, packaging/aging, and nanotoxicity concerns. This extensive, clinical translation focused review of TNTs modified Ti implants aims to foster improved understanding of key research gaps and advances, informing future research in this domain.
Keywords: TiO2 nanotubes; anodization; clinical translation; implants; local therapy; titanium.