Anodic Growth and Biomedical Applications of TiO₂ Nanotubes

Over the past decades, self-assembled, vertically-aligned nanotubes have been generated on metallic substrates via anodization, which attracted significant scientific interest for a broad range of applications. These nano-tubular structures integrate highly controllable geometry at the nano-scale with fascinating chemical and biological properties. In this review, we first discussed mechanistic aspects of nanotube growth primarily on titanium (Ti) substrates by controlled anodization, a relatively inexpensive and scalable electrochemical process. We thoroughly reviewed electrochemical conditions that led to formation of self-assembled, vertically-aligned nano-tubular layers as they apply primarily to Ti substrates; we also reviewed anodization conditions that have led to formation of nanotubes on zirconium and various Ti alloys. We discussed how to adjust a set of anodization parameters to fine-tune the geometry of vertically oriented titania (TiO₂) nanotubes, such as nanotube diameter, wall thickness, and length. We critically analyzed the key anodization parameters in the literature, including applied voltage, anodization duration, voltage ramp, electrolyte composition and concentration, electrolyte pH, electrolyte temperature, and electrolyte fluoride and water concentrations. Lastly, we discussed the promising properties of anodically grown TiO₂ nano-tubular arrays for a wide range of biomedical applications, including directing cell bioactivity, anti-bacterial efficacy, modulating deposition of hydroxyapatite, drug delivery, biosensors, and orthopedic implants (in vivo). We highlighted ongoing in vitro and in vivo studies on the effects of nanotube geometry and aspect ratio on their hydrophilicity and interactions with biological entities at the protein, cellular and tissue level.