Understanding and optimizing the antibacterial functions of anodized nano-engineered titanium implants.

Nanoscale surface modification of titanium-based orthopaedic and dental implants is routinely applied to augment bioactivity, however, as is the case with other cells, bacterial adhesion is increased on nano-rough surfaces. Electrochemically anodized Ti implants with titania nanotubes (TNTs) have been proposed as an ideal implant surface with desirable bioactivity and local drug release functions to target various conditions. However, a comprehensive state of the art overview of why and how such TNTs-Ti implants acquire antibacterial functions, and an in-depth knowledge of how topography, chemistry and local elution of potent antibiotic agents influence such functions has not been reported. This review discusses and details the application of nano-engineered Ti implants modified with TNTs for maximum local antibacterial functions, deciphering the interdependence of various characteristics and the fine-tuning of different parameters to minimize cytotoxicity. An ideal implant surface should cater simultaneously to ossoeintegration (and soft-tissue integration for dental implants), immunomodulation and antibacterial functions. We also evaluate the effectiveness and challenges associated with such synergistic functions from modified TNTs-implants. Particular focus is placed on the metallic and semi-metallic modification of TNTs towards enabling bactericidal properties, which is often dose dependent. Additionally, there are concerns over the cytotoxicity of these therapies. In that light, research challenges in this domain and expectations from the next generation of customizable antibacterial TNTs implants towards clinical translation are critically evaluated. STATEMENT OF SIGNIFICANCE: One of the major causes of titanium orthopaedic/dental implant failure is bacterial colonization and infection, which results in complete implant failure and the need for revision surgery and re-implantation. Using advanced nanotechnology, controlled nanotopographies have been fabricated on Ti implants, for instance anodized nanotubes, which can accommodate and locally elute potent antibiotic agents. In this pioneering review, we shine light on the topographical, chemical and therapeutic aspects of antibacterial nanotubes towards achieving desirable tailored antibacterial efficacy without cytotoxicity concerns. This interdisciplinary review will appeal to researchers from the wider scientific community interested in biomaterials science, structure and function, and will provide an improved understanding of controlling bacterial infection around nano-engineered implants, aimed at bridging the gap between research and clinics.