Gentamicin-Releasing Titania Nanotube Surfaces Inhibit Bacteria and Support Adipose-Derived Stem Cell Growth in Cocultures.

Abstract

Infection is the second leading cause of failure of orthopedic implants following incomplete osseointegration. Materials that increase the antimicrobial properties of surfaces while maintaining the ability for bone cells to attach and proliferate could reduce the failure rates of orthopedic implants. In this study, titania nanotubes (Nts) were modified with chitosan/heparin polyelectrolyte multilayers (PEMs) for gentamicin delivery. The antimicrobial activity of the surfaces was tested by coculturing bacteria with mammalian cells. Over 60% of gentamicin remained on the surface after an initial burst release on the first day. Antimicrobial activity of these surfaces was determined by exposure to Gram-positive Staphylococcus aureus (S. aureus) and Gram-negative Escherichia coli (E. coli) for up to 24 h. Gentamicin surfaces had less live E. coli and S. aureus by 6 h and less E. coli by 24 h compared to Nt surfaces. S. aureus and human adipose-derived stem cells (hADSCs) were cocultured on surfaces for up to 7 days to characterize the so-called "race to the surface" between bacteria and mammalian cells, which is hypothesized to ultimately determine the outcome of orthopedic implants. By day 7, there was no significant difference in bacteria between surfaces with gentamicin adsorbed on the surface and surfaces with gentamicin in solution. However, gentamicin delivered in solution is toxic to hADSCs. Alternatively, gentamicin presented from PEMs enhances the antimicrobial properties of the surfaces without inhibiting hADSC attachment and cell growth. Delivering gentamicin from the surfaces is therefore superior to delivering gentamicin in solution and represents a strategy that could improve the antimicrobial activity of orthopedic implants and reduce risk of failure due to infection, without reducing mammalian cell attachment.