Gentamicin-Loaded TiO2 Nanotubes as Improved Antimicrobial Surfaces for Orthopedic Implants

Abstract

Titanium oxide nanotube arrays are extremely promising materials for localized drug delivery in orthopedic implants due to their excellent properties and facile preparation. TiO 2 nanotubes can act as an effective drug reservoir to prevent bacterial colonization and implant infection and, at the same time, could promote tissue regeneration and effective osseointegration. Here, highly ordered TiO 2 nanotubes (NTs) were synthesized by electrochemical anodization of titanium foils and the process parameters were varied in order to obtain a large range of NT diameters to evaluate its influence. The effect of NTs' diameter on gentamicin loading/release and on osteosarcoma cell and bacterial adhesion was assessed. Anodization was confirmed as an easy and effective method to prepare highly ordered, open top nanotubes with predictable diameter as a function of imposed voltage. A lower amount of bacteria Staphylococcus Aureus adhesion was found on unloaded NTs surfaces at 24 h. When gentamicin was loaded, protracted release and antibacterial action was observed and bacteria adhesion was prevented on all NTs dimension. However, higher cell proliferation and a more favorable cell morphology was observed on smaller nanotubes, to support the indication toward a reduction in NTs diameter for the preparation of effective implant surfaces.

Anodic TiO2 Nanotubes: Tailoring Osteoinduction via Drug Delivery

“…For drug delivery on TiO 2 nanotubular bio-implants, so far a high number of investigations has mainly focused on antibacterial effect using (i) metal ions or nanoparticles (Ag [ 241 , 242 , 243 ], silver oxide - Ag 2 O [ 244 , 245 ], gold - Au [ 122 ], selenium - Se [ 239 ], Zn [ 246 ], zinc oxide - ZnO [ 247 ], Cu [ 248 ], Sr [ 249 , 250 ], tantalum (Ta) and Cu [ 124 ], Zn-Ag [ 251 ], Sr-Ag [ 250 ], or calcium and phosphorus - Ca-P [ 252 , 253 ]), (ii) drugs (vancomycin [ 36 ], gentamicin [ 254 ], metformin [ 255 ], alendronate [ 256 ], simvastatin [ 257 ]) or (iii) polymers (polyaniline [ 258 ], chitosan [ 210 , 238 ]) to provide a contamination/infection-reduced condition beneficial for osseointegration (see Figure 11 and Table 2 ).…”

“…For targeting antibacterial effect combined with an improved osteoinduction, the release mechanism and release rate of gentamicin [ 254 , 271 ], metformin [ 255 ], ibuprofen [ 37 ] from TiO 2 NTs have been extensively studied [ 127 , 229 , 236 ]. Further, a variety of combination sets of drugs and NT decorations has been designed and suggested to get the synergistic effects on antibacterial effect and improved osteoinduction.…”

“…Further, a variety of combination sets of drugs and NT decorations has been designed and suggested to get the synergistic effects on antibacterial effect and improved osteoinduction. Draghi et al [ 254 ] confirmed that loading gentamicin into the smaller diameter (31 nm) NTs resulted in a protracted release and antibacterial action together with improved cell adhesion and proliferation of an osteosarcoma cell line. Lai et al [ 257 ] tailored the release of simvastatin from chitosan/gelatin-coated TiO 2 NTs improving osteoblast differentiation and inhibition of osteoclastic differentiation (compared to free-drug bare NTs).…”

Trends in Managing Cardiac and Orthopaedic Device-Associated Infections by Using Therapeutic Biomaterials

“…Gentamicin-based coatings are the most studied owing to the well-established use of this antibiotic in the clinic for MSSA bone-related infections treatments [ 86 , 87 , 88 , 89 , 90 ]. Vancomycin, commonly used to treat MRSA infections, has also been incorporated into implant coatings.…”

Electrophoretic Deposition of Biocompatible and Bioactive Hydroxyapatite-Based Coatings on Titanium

“…The choice was made to employ a strategy that utilizes a carrier polymeric matrix e.g., chitosan to deliver in situ chosen antibiotic-gentamicin. Implementation of gentamicin sulfate, as an antimicrobial agent, attracted extreme interest in the biomaterials' field, due to gentamicin broad antibacterial spectrum of action [117][118][119][120][121][122][123]. With the aim to obtain antibacterial and biocompatible coatings on titanium, containing gentamicin as antimicrobial agents, EPD was employed [124][125][126][127].…”