Nanotube Generation on Titanium Kirschner Wire and Electrophoretic Deposition of Gentamicin and Chitosan

Periprosthetic joint infection (PJI) occurs in around 1-2% of primary total hip and knee arthroplasties, but rates of PJI can be greater than 20% in individuals with a combination of demographic, surgical, and/or comorbidity risk factors. Development of PJI can lead to devastating complications including requirement of multiple operations, poor outcomes and morbidity, and mortality. Systemic antimicrobials are routinely utilized as a preventative measure and treatment for PJI. However, systemic drug treatments can provide low bioavailability of antimicrobial drugs around the implant and can fail to prevent or eradicate the infection. Therefore, the development of localized drug delivery systems is of great clinical signifcance. Titanium (Ti) is known to form a nanotubular oxide layer under electric potential; this layer can be exploited as pockets for localized drug delivery. The aim of the present work was to use electrophoretic deposition (EPD) as drug loading and coating of nantoubes (NT) on a mouse femural nail to establish a local application of antibiotic capable of prolonged antimicrobial drug delivery. The NTs were created on Ti wire with two-step anodization process and were characterized by a 100 nm diameter and 7 µm length. This process allowed a highly ordered nanotube morphology maintaining a high diameter but with lower variability with respect to the other methods tested. EPD resulted in a higher amount of gentamicin deposited with all parameters tested as compared to the air-dry method, up to 10x higher values were obtained. The amount of antibiotic with EPD was controllable by adjusting the two parameters of the deposition, increasing voltage and duration led to more drug loaded. The application of a crosslinked chitosan layer allowed logarithmic release kinetics for up to 3 days. Gentamicin-loaded Ti wires signifcantly inhibited S. aureus growth in liquid culture and resulted in a larger elliptical inhibition zone (4.5 cm x 3.5 cm) compared to anodized but unloaded wires. Toxicity analysis resulted in 93% viability in osteoblast cultures. Antibiotic loaded Ti nanotubes created on Ti surface might represent a powerful tool for prevention of PJI; we plan to test this technology next in a murine PJI model.