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Local delivery of antimicrobial peptides using self-organized TiO₂ nanotubes for implant-related infections Ma, Menghan

Abstract

Among the various complications that lead to the failure of orthopaedic implants, prosthetic-related infections have been reported as one of the major causes. Local delivery of antimicrobial agents through the implants surface is an ideal solution to the peri-implant infection problem. Due to the increasing resistance of pathogens to the current therapy utilizing antibiotics, developing novel antimicrobial agents has received much attention recently. Among the potential alternatives are the antimicrobial peptides (AMPs). Because of their broad-spectrum bactericidal ability, low toxicity and immunogenicity, as well as complex killing mechanisms, AMPs have much lower possibility of developing resistance than traditional antibiotics. In the past decade, fabrication of TiO₂ nanotubular structures by anodization method has attracted great interests because of its controllable, reproducible results as well as the simple process. In light of their high surface-to-volume ratio, controllable dimensions, excellent biocompatibility, adjustable wettability and other promising properties, TiO₂ nanotubes are considered as an ideal carrier for drugs. In the current study, self-organized, vertically-oriented TiO₂ nanotubes were successfully prepared by anodization method in both water based electrolytes (phosphoric acid based and ammonium sulphate based electrolytes) and organic based electrolytes (Glycerol based and Ethylene glycol based electrolytes). The nanotube coatings prepared in ethylene glycol based electrolytes, with ~80nm diameter and ~7 μm thickness, were selected for the drug delivery purpose. HHC-36, one of the most potent broad-spectrum AMPs with the sequence of (KRWWKWWRR) was loaded onto the titanium dioxide nanotubes via a simple vacuum assisted physical adsorption method. Antimicrobial activity test against Gram-positive bacteria (Staphylococcus aureus) demonstrated that this novel AMP-loaded nanotube surface significantly inhibited bacteria proliferation and effectively reduced bacterial adhesion on the surface. It was also found that the antimicrobial activities of the samples were highly dependent on the drug loading conditions. By changing the loading conditions, the bacteria killing rate after 4 hour incubation increased dramatically from 90% to 99.9%. In vitro study showed that the AMP-loaded nanotube samples are not cytotoxic for MG-63 osteoblast-like cells.

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