Tailoring the immuno-responsiveness of anodized nano-engineered titanium implants

Owing to its biocompatibility and corrosion resistance, titanium is one of the most commonly used implantable biomaterials. Numerous in vitro and in vivo investigations have established that titanium surfaces with a nanoscale topography outperform conventional smooth or micro-rough surfaces in terms of achieving desirable bonding with bone (i.e. enhanced bioactivity). Among these nanoscale topographical modifications, ordered nanostructures fabricated via electrochemical anodization, especially titania nanotubes (TNTs), are particularly attractive. This is due to their ability to augment bioactivity, deliver drugs and the potential for easy/cost-effective translation into the current implant market. However, the potential of TNT-modified implants to modulate the host immune-inflammatory response, which is critical for achieving timely osseointegration, remains relatively unexplored. Such immunomodulatory effects may be achieved by modifying the physical and chemical properties of the TNTs. Furthermore, therapeutic/bioactive enhancements performed on these nano-engineered implants (such as antibacterial or osteogenic functions) are likely to illicit an immune response which needs to be appropriately controlled. The lack of sufficient in-depth studies with respect to immune cell responses to TNTs has created research gaps that must be addressed in order to facilitate the design of the next generation of immuno-modulatory titanium implants. This review article focuses on the chemical, topographical and mechanical features of TNT-modified implants that can be manipulated in order to achieve immuno-modulation, as well as providing an insight into how modulating the immune response can augment implant performance.