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

Abstract

Infection is one of the major causes of failure of orthopedic implants. Our previous study demonstrated that nanotube modification of the implant surface, together with nanotubes loaded with quaternized chitosan (hydroxypropyltrimethyl ammonium chloride chitosan, HACC), could effectively inhibit bacterial adherence and biofilm formation in vitro. Therefore, the aim of this study was to further investigate the in vitro cytocompatibility with osteogenic cells and the in vivo anti-infection activity of titanium implants with HACC-loaded nanotubes (NT-H). The titanium implant (Ti), nanotubes without polymer loading (NT), and nanotubes loaded with chitosan (NT-C) were fabricated and served as controls. Firstly, we evaluated the cytocompatibility of these specimens with human bone marrow-derived mesenchymal stem cells in vitro. The observation of cell attachment, proliferation, spreading, and viability in vitro showed that NT-H has improved osteogenic activity compared with Ti and NT-C. A prophylaxis rat model with implantation in the femoral medullary cavity and inoculation with methicillin-resistant Staphylococcus aureus was established and evaluated by radiographical, microbiological, and histopathological assessments. Our in vivo study demonstrated that NT-H coatings exhibited significant anti-infection capability compared with the Ti and NT-C groups. In conclusion, HACC-loaded nanotubes fabricated on a titanium substrate show good compatibility with osteogenic cells and enhanced anti-infection ability in vivo, providing a good foundation for clinical application to combat orthopedic implant-associated infections.

Bone implants: Staving off infection

A new weapon using ultrasmall tubes loaded with a broad spectrum antibacterial agent is now available against implant-associated infections. Metal rods inserted into the bone cavity speed up recovery from tibia and femur bone fractures. However, bacterial adhesion and buildup on implant surfaces may induce infection, especially in the treatment of open fractures, causing implant failure. To prevent infection, Tingting Tang and coworkers from Shanghai Jiao Tong University, China, have developed titanium nanotube arrays loaded with the antimicrobial agent quaternarized chitosan. They generated the nanotubes by electrochemically modifying the implant surface before adding the chitosan derivative. The arrays promoted bone cell attachment, proliferation, and growth to a greater extent than unmodified titanium in human cells. Moreover, they exhibited enhanced anti-infection activity when implanted in rat models inoculated with methicillin-resistant Staphylococcus aureus bacteria.

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