Professor and Chair George Mason University, United States
Introduction: Bacterial infections are a primary challenge associated with titanium-based biomedical implants. Bacterial adhesion kickstarts infections on titanium implants and develops complex, multi-species biofilms coating the implant surfaces. These biofilms pose a significant challenge due to their heightened resistance against antibiotics, making them extremely difficult to eliminate. The intricate microbial makeup and three-dimensional structure of biofilms contribute to their tolerance of antibiotics. Consequently, severe inflammatory responses can arise, potentially leading to implant failure and complications. While titanium nanotube (TiNT) surfaces improve biocompatibility, preventing bacterial adhesion and biofilm formation remains challenging. This study presents a novel approach to combat implant-associated infections by functionalizing TiNTs with self-assembling peptides. The objective was to develop antibacterial surfaces by covalently conjugating the self-assembling dipeptide N-fluorenylmethyloxycarbonyl-diphenylalanine (Fmoc-FF) onto TiNT surfaces, leveraging the synergistic effects of nano topography and inherent antibacterial properties of Fmoc-FF peptides. This functionalization aimed to impart antibacterial properties to the surface while retaining the beneficial nanotube topography, enhancing bioactivity.
Materials and
Methods: Fmoc-FF peptides were covalently conjugated onto TiNT surfaces using established protocols. Surface characterization techniques, including X-ray photoelectron spectroscopy (XPS), Fourier-transform infrared spectroscopy (FT-IR), energy-dispersive X-ray spectroscopy (EDS), and scanning electron microscopy (SEM), were employed to confirm successful functionalization. Antibacterial evaluation was conducted against Gram-positive Staphylococcus aureus and Gram-negative Pseudomonas aeruginosa strains. Bacterial adhesion and biofilm formation assays were performed to assess the antibacterial efficacy of the Fmoc-FF-conjugated TiNT surfaces compared to unmodified TiNTs.
Results, Conclusions, and Discussions: Surface characterization techniques confirmed the successful conjugation of Fmoc-FF onto TiNT surfaces, with new peaks corresponding to nitrogen, silicon, and various functional groups observed on the Fmoc-FF-TiNT surfaces. Remarkably, the antibacterial evaluation revealed that the Fmoc-FF-conjugated TiNT surfaces significantly inhibited bacterial adhesion and biofilm formation against both S. aureus and P. aeruginosa compared to unmodified TiNTs. This enhanced antibacterial efficacy is attributed to the synergistic effects of the nanotube topography and the inherent antibacterial properties of the self-assembling Fmoc-FF dipeptide. The findings of this study highlight the potential of Fmoc-FF-conjugated TiNT surfaces for developing advanced antibacterial coatings for a wide range of biomedical implants, such as orthopedic and dental implants. This innovative approach can improve these life-changing medical devices' long-term performance and success by preventing implant-associated infections and biofilm formation. Furthermore, the versatility of self-assembling peptides like Fmoc-FF presents exciting opportunities for exploring their applications in other biomedical fields. The Fmoc-FF peptides, in conjugation with TiNTs, can inhibit biofilm formation, eradicate pre-existing biofilms, and kill bacteria through multiple mechanisms, including membrane disruption, oxidative stress, and interference with cellular processes.
