Behavior of in vitro, in vivo and internal motion of micro/nano particles of titanium, titanium oxides and others

To clarify the effect of micro/nanosizing of materials onto biological organism, the particle size dependence of reaction of cells and tissue as investigated by both biochemical cell functional test and animal implantation test. Especially for nanoparticles the behavior of invasion and internal diffusion inside body was visualized using an XSAM (X-ray Scanning Analytical Microscope). The increase of specific surface area is usually counted as nanosizing effect which causes the enhancement of chemical reactivity and therefore toxicity of materials such as carcinogenicity found in 500 nm Ni particles for the long term implantation in the soft tissue of rat. Even biocompatible materials such as Ti and TiO2 shows stimulus with the decrease of particle size. They cause phagocytosis to cells and inflammation to tissue when the size of particles is below 3 mu m. For the size below 50 nm, they may invade into the internal body through the respiratory or digestive system and diffuse inside body. After compulsory exposure test of 30 nm TiO2 particles through the respiratory system, the Ti mapping by XSAM showed the internal diffusion inside the whole body. Nanoparticles injected from caudal vein diffused with time course to lung, liver and spleen. The uptake of 30 nm TiO2 particles through the digestive system and diffusion into these organs was also confirmed. These phenomena observed in biocompatible or bioinert materials are the nonspecific, physical particle and shape effects which occur independent of materials. Nanoparticles might be the objects whose existence has not been assumed by the living body defense system.