| Dr. Stefan A. Esenwein1, Dr. Denise Bogdanski2, Prof. Michael Wilhelm3, Prof. Matthias Epple4, Dr. Jürgen Wittsiepe3, Prof. Gert Muhr1, Dr. Oleg Prymak4, Prof. Michael Pohl5 and Prof. Manfred Köller2, 1Traumatology and Orthopaedic Surgery, BG Trauma Center Bergmannsheil - Ruhr University of Bochum, Bürkle-de-la-Camp-Platz 1, Bochum, D-44789, Germany, 2Traumatology and Orthopaedic Surgery - Dept. of Research, BG Trauma Center Bergmannsheil - Ruhr University of Bochum, Bürkle-de-la-Camp-Platz 1, Bochum, D-44789, Germany, 3Department of Hygiene, Social and Environmental Medicine, Ruhr University of Bochum, Universitätsstraße 150, Gebäude MA, Bochum, D-44801, Germany, 4Institute of Anorganic Chemistry, University of Duisburg-Essen, Universitätsstraße 5-7, Essen, D-45117, Germany, 5Institute of Materials -Dept. of Materials Testing, Ruhr University of Bochum, Universitätsstraße 150, Geb. IA, Bochum, D-44801, Germany
Introduction: Nickel-titanium shape memory alloys (NiTi-SMA) are of biomedical interest due to an unusual range of pure elastic deformability (superelasticity) and the shape memory effect which allows this material to return to a predictable previously memorized shape after external changes in temperature. Before NiTi-SMAs can be used as long-term implants, their biocompatibility level must be assessed. In most cases medical implants are initially exposed to a blood-containing microenvironment. The early interaction of leukocytes with implant surfaces and the potential release of Ni ions represent important aspects of biocompatibility and early released mediators are intimately involved in this process.
Methods: Two different leukocyte fractions polymorphonuclear neutrophil leukocytes (PMN) and peripheral blood mononuclear cells (PBMC) were isolated from peripheral blood of healthy volunteers using discontinuous double Ficoll-gradients. Isolated cells were adjusted to 1x 106 cells /ml supplemented cell culture medium. Isolated PMN or PBMC (1 x 106 cells) were added to the NiTi disks placed in wells of 24-well cell culture plates and were incubated for 24h using cell culture conditions (37°C, 5 % CO2, humidified atmosphere). Cell free supernatants (conditioned supernatants) were analyzed for cytokine content (IL-1ra; IL-6, IL-8, TNF-a, GM-CSF, IFN-g) by ELISA-method. For Ni-release experiments NiTi samples were incubated in phosphate buffer for different periods (up to three weeks) at 37°C, partly, etched samples were included. Ni ion release was analyzed by atomic absorption spectrometry. In addition, cytokine release studies were performed in the presence of exogeneously added Ni ions (2.4 µg/l - 24 mg/l).
Results: In comparison to the control incubations without NiTi samples a significant, but low increase in the release of IL-1ra, IL-6 and IL-8 was observed in the presence of NiTi samples. The Ni ion release ranged from 60 µg/l (NiTi-sample) to 8 mg/l (etched NiTi sample). Leukocyte incubations in the presence of exogeneously added Ni ions up to 2.4 mg/l did not lead to a significant modulation in cytokine generation. An increase in cytokine release was only observed at extremely high Ni ion concentrations (24 mg/l).
Conclusions: Due to its low Ni ion release, non-etched NiTi shows a good biocompatibility. This results mainly from its stable and tight intermetallic bounded structure, its chemically stable and homogeneous TiO2 surface layer, and its corrosion resistance similar to other titanium alloys. The Ni ion release of the non-etched samples led to a low increase in cytokine production which showed no influence on cell activation. |