Improved osteogenic activity and inhibited bacterial biofilm formation on andrographolide-loaded titania nanotubes

Delivery of local drugs with a titania nanotube is an attractive approach to combat implant-related infection. Our earlier study has confirmed that nanotubes loaded with gentamicin could significantly improve the antibacterial ability. On this basis, the used andrographolide in this paper has a high antibacterial activity, which cannot only avoid the evolution of antibiotic-resistant bacteria but also has simultaneously excellent biocompatibility with osteogenic cells.

Two mg of andrographolide was loaded into titania nanotubes, which were fabricated into different diameters (50 and 100 nm) and 200 nm length by the method of lyophilization and vacuum drying. We chose a standard strain, Staphylococcus epidermidis (American Type Culture Collection 35984), and two clinical isolates, S. aureus 376 and S. epidermidis 389 to research the bacterial adhesion at 6, 12 and 24 hours and biofilm formation at 48, and 72 hours on the andrographolide-loaded nanotubes (NT-A) using the diffusion plate method. Smooth titanium (smooth Ti) and nanotubes with no drug loading (NT) were also inclusive and analyzed. Furthermore, the Sprague-Dawley (SD) rats mesenchymal stem cells were used to assess the influence of nanotubular topographies on the osteogenic differentiation of mesenchymal stem cells.

Our results showed that NT-A could inhibit bacterial adhesion and biofilm formation on implant surfaces. NT-A and NT, especially those with 100 nm diameters, were found to significantly promoted cell attachment, proliferation, diffusion, and osteogenic differentiation when compared with smooth Ti, while the same diameter in NT-A and NT did not differ.

Titania nanotube modification and andrographolide loading can significantly improve the antibacterial ability and osteogenic activity of orthopedic implants. Nanotubes-based local delivery could be a promising strategy for combating implant-associated infection.