Biocompatible antibiotic-coupled nickel-titanium nanoparticles as a potential coating material for biomedical devices.

ABSTRACT

The challenges facing metallic implants for reconstructive surgery include the leaching of toxic metal ions, a mismatch in elastic modulus between the implant and the treated tissue, and the risk of infection. These problems can be addressed by passivating the metal surface with an organic substrate and incorporating antibiotic molecules. Nitinol (NiTi), a nickel-titanium alloy, is used in devices for biomedical applications due to its shape memory and superelasticity. However, unmodified NiTi carries a risk of localized nickel toxicity and inadequately supports angiogenesis or neuroregeneration due to limited cell adhesion, poor biomineralization, and little antibacterial activity. To address these challenges, NiTi nanoparticles were modified using self-assembled phosphonic acid monolayers and functionalized with the antibiotics ceftriaxone and vancomycin via the formation of an amide. Surface modifications were monitored to confirm that phosphonic acid modifications were present on NiTi nanoparticles and 100% of the samples formed ordered films. Modifications were stable for more than a year. Elemental composition showed the presence of nickel, titanium, and phosphorus (1.9% for each sample) after surface modifications. Dynamic light scattering analysis suggested some agglomeration in solution. However, scanning electron microscopy coupled with energy-dispersive X-ray spectroscopy confirmed a particle size distribution of <100 nm, the even distribution of nanoparticles on coverslips, and elemental composition before and after cell culture. B35 neuroblastoma cells exhibited no inhibition of survival and extended neurites of approximately 100 µm in total length when cultured on coverslips coated with only poly-l-lysine or with phosphonic acid-modified NiTi, indicating high biocompatibility. The ability to support neural cell growth and differentiation makes modified NiTi nanoparticles a promising coating for surfaces in metallic bone and nerve implants. NiTi nanoparticles functionalized with ceftriaxone inhibited Escherichia coli and Serratia marcescens (SM6) at doses of 375 and 750 µg whereas the growth of Bacillus subtilis was inhibited by a dose of only 37.5 µg. NiTi-vancomycin was effective against B. subtilis at all doses even after mammalian cell culture. These are common bacteria associated with infected implants, further supporting the potential use of functionalized NiTi in coating reconstructive implants.