Inhibited bacterial biofilm formation and improved osteogenic activity on gentamicin-loaded titania nanotubes with various diameters

Abstract

Titania nanotubes loaded with antibiotics can deliver a high concentration of antibiotics locally at a specific site, thereby providing a promising strategy to prevent implant-associated infections. In this study we have fabricated titania nanotubes with various diameters (80, 120, 160, and 200 nm) and 200 nm length via electrochemical anodization. These nanotubes were loaded with 2 mg of gentamicin using a lyophilization method and vacuum drying. A standard strain, Staphylococcus epidermidis (American Type Culture Collection 35984), and two clinical isolates, S. aureus 376 and S. epidermidis 389, were selected to investigate the anti-infective ability of the gentamicin-loaded nanotubes (NT-G). Flat titanium (FlatTi) and nanotubes with no drug loading (NT) were also investigated and compared. We found that NT-G could significantly inhibit bacterial adhesion and biofilm formation compared to FlatTi or NT, and the NT-G with 160 nm and 200 nm diameters had stronger antibacterial activity because of the extended drug release time of NT-G with larger diameters. The NT also exhibited greater antibacterial ability than the FlatTi, while nanotubes with 80 nm or 120 nm diameters had better effects. Furthermore, human marrow derived mesenchymal stem cells were used to evaluate the effect of nanotubular topographies on the osteogenic differentiation of mesenchymal stem cells. Our results showed that NT-G and NT, especially those with 80 nm diameters, significantly promoted cell attachment, proliferation, spreading, and osteogenic differentiation when compared to FlatTi, and there was no significant difference between NT-G and NT with the same diameter. Therefore, nanotube modification and gentamicin loading can significantly improve the antibacterial ability and osteogenic activity of orthopedic implants.

Cytocompatibility with osteogenic cells and enhanced in vivo anti-infection potential of quaternized chitosan-loaded titania nanotubes

“… 12 Our previous in vitro and in vivo studies revealed that gentamicin-loaded nanotubes on titanium substrates exhibited evident antibacterial activity for the two bacterial strains mentioned above. 13 , 14 However, the resistance to β-lactamase, aminoglycoside, lincosamide, trimethoprim, macrolide, tetracycline, and sulfonamide antibiotics in S. aureus and S. epidermidis is widespread in current orthopedics surgery. 15 , 16 Therefore, implants with good antibacterial capability, especially under methicillin-resistant stapthylococci infection, is critical to the successful fixation and healing of bone fractures in current orthopedic surgery.…”

“…Although the in vitro antibacterial activity of HACC-loaded nanotubes with a diameter of 200 nm was reported to be better than those with a diameter of 160 nm, 24 the cytocompatibility had a negative correlation with the diameter of the nanotubes. 13 Therefore, we fabricated TNTs with 160 nm diameters on titanium plates and rods for the consideration of both the antibacterial capability and cytocompatibility in this study. Quaternized chitosan with a degree of substitution of 26% was loaded into these nanotubes to form an effective local antibiotic delivery system, and the in vitro cytocompatibility was assessed.…”

Microbiological and Cellular Evaluation of a Fluorine-Phosphorus-Doped Titanium Alloy, a Novel Antibacterial and Osteostimulatory Biomaterial with Potential Applications in Orthopedic Surgery

“…Titanium alloys, mainly Ti-6Al-4V, are commonly used in orthopedic surgery and traumatology due to their well-known physico-chemical properties and biocompatibility (16)(17)(18). To date, most of the methods used to manufacture nanotubular oxide layers with potential biomedical applications have been implemented in pure titanium (19)(20)(21)(22)(23)(24)(25)(26). Recently, we demonstrated that fluorine (F) doping during the anodizing process of Ti-6Al-4V decreases staphylococcal adherence by about 50% (27) and that F doping, together with the nanostructure resulting from the anodizing process, improves the osseointegrative properties by favoring matrix mineralization of osteoblastic cells (28).…”

Overview of Nanoparticle Coating of Dental Implants for Enhanced Osseointegration and Antimicrobial Purposes

“…They also tested the osteogenic differentiation ability of the prepared gentamicinloaded nanotubes using human marrow derived mesenchymal stem cells; their results revealed significantly promoted cell attachment, proliferation, spreading, and osteogenic differentiation when compared to titania. Then results also showed the efficiency of titania nanotubes loaded with antibiotics for local delivery to a specific site and presenting a promising strategy to prevent implantassociated infections (50).…”