Biochemical and Pathological Responses of Cells and Tissue to Micro- and Nanoparticles from Titanium and other Materials

Biocompatible titanium (Ti) causes inflammation when in the form of abraded fine particles, whereas asbestos, which is a type of clay mineral, induces mesothe-lioma after long-term, high-level exposure. In addition to these materials' properties, such as toxicity or biocompatibility, these phenomena may be seen to occur as a result of the "particle effect". The cytotoxicity of fine particles of Ti, Fe, Ni and TiO2 was investigated in vitro using human neutrophils as probe cells, and also with the tissue reaction in-vivo implantation test. Biochemical functional analyses of cell survival rate, lactate dehydrogenase (LDH) activities, superoxide anion, cytokines and the microscopic observation of cellular morphology showed that the stimulatory effects on neutrophils and inflammation in soft tissue became more prominent as the particle size became smaller (<100 m̈m). Moreover, such effects were especially pronounced for particles <10 m̈m (about cell size), when phagocytosis was induced. Inductively coupled plasma elemental analysis showed dissolution from Ti particles to be negligible. Results with Fe were quantitatively similar to those with Ti, despite Fe being soluble. Taken together, these results indicated that the stimulus produced is based, non-specifically, on the physical size and shape effect of particles, and is more pronounced on the micro/nano scale. This is different from the material-dependent, chemical toxicity effects that are caused by ionic dissolution and normally dominant in bulk materials.