Effects of Nitinol Surface Treatments and Ethylene Oxide Sterilization on Human Lymphocyte Proliferation

Surface treatment and sterilization are those critical protocols in the manufacturing of implant devices that can eventually predetermine the outcome of implantation. Biological performance of well characterized Nitinol surfaces (mechanically polished, chemically etched, aged in boiling water, heat treated, and electropolished) was evaluated using human peripheral blood lymphocyte proliferation test. To assess the effect of sterilization, two types of sterilization were used, UV and ethylene oxide. Incubation of PBL with Nitinol samples demonstrated 1532% higher proliferation compared to controls (cells + Con A, no metals). In the case of UV sterilized samples, higher Ni surface concentrations resulting in higher Ni release caused statistically more significant stimulation. This stimulation was similar to the observed in the case of ethylene oxide sterilized samples, which, however, induced zero Ni concentration in medium. The control Ti samples also caused a 15% higher proliferation in all individuals compared to stimulation with ConA alone. Pure nickel induced significant suppression that varied from individual to individual in the range 40 to ~100 %. Distinct stimulatory and suppressive effects exerted by Ni-containing samples on lymphocytes, cells of immune system fall in the category of the U-shaped dose response to toxic substances. A 15-32% increase in proliferation of ConA stimulated PBL by very low metal ion concentrations induced in biological solutions as well as by EtO sterilized samples is interpreted as an enhanced immune response. The results obtained using lymphocyte stimulation are discussed together with the results of an earlier study on carcinogenic potential of Nitinol alloys in rats (A. Starokha. New technologies in the treatment of rhinosinusitis utilizing superelastic shape memory implants, D.Sc. Thesis, Sankt-Petersburg, 1998).