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 adiposederived 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.

Effect of Different Local Antibiotic Regimens on Prevention of Postoperative Infection in Clean Surgical Wounds: A Systematic Review and Network Meta-analysis

“…Topical gentamicin has several advantages: it does not damage renal function and has a low risk of drug-resistant pathogens, it kills bacteria by inhibiting protein synthesis, and it destroys the stability of the bacterial bilayer membrane 24 . Wigmosta et al 42 discovered that delivering gentamicin from the surface is superior to delivering gentamicin in a solution, which could improve the antimicrobial activity of orthopedic implants and lower the risk of infection-induced failure without reducing mammalian cell attachment. Further, gentamicin and curcumin-loaded lipid-polymer hybrid nanoparticles have excellent antibacterial properties and are promising antibacterial agents for the treatment of chronic infections and intracellular bacteria 43 .…”

In vitro testing and efficacy of poly‐lactic acid coating incorporating antibiotic loaded coralline bioceramic on Ti6Al4V implant against Staphylococcus aureus

“…Drug delivery coating systems can provide direct delivery of pharmaceuticals at the targeted bone‐implant interface. In particular, polymeric matrix‐based drug delivery coating systems have been designed to provide solutions for implant related infections (Inzana et al., 2016; Pan et al., 2018), osteomyelitis treatments and also for the inhibition of bacterial biofilm formation on the implant surface (Wigmosta et al., 2021).…”

“…Long term, high‐dose Gm therapy has been associated with bacterial antibiotic resistance (Ben‐Nissan et al., 2013; Ribeiro et al., 2012). Additionally, it has been reported that various antibiotics including gentamycin, rifampicin, penicillin, and streptomycin cause dose‐dependent negative effects on the biological properties and regenerative potential of human ADSCs including growth, proliferation, and differentiation (Rady et al., 2020; Skubis et al., 2017; Wigmosta et al., 2021). To avoid negative effects on ADSC, the antibiotics should be applied at adequate concentration for a sufficient time (Lotfi et al., 2020).…”