**4. Counter-Indications**

There is inevitably some sort of interaction between the organic or inorganic materials and the biological environment when individual or composite biomaterials are put in contact with the tissues and fluids of the human body. The basic clinical research may decide that the materials should not cause any local or systemic adverse reactions. Recent studies exposed that nanosized materials can easily penetrate biological membranes of normal cells and enter vascular system to facilitate redistribution in different tissues. Nanomaterials, which by themselves are not very harmful, could become toxic if are ingested in higher concentration. The toxicity of metal based biomaterials to the liver is an important basis for the safety assessment of nanosized materials. Metal based nanoparticles release ions which may enter the cells and affect the functions of organelles, leading to liver injury. Various factors including amount, composition, pH, and fabrication techniques may decide the compatibility and cytotoxicity of biomaterials. The research is ongoing to improve the existing technologies which may produce highly compatible substitutes without producing adverse effects.
