The biological activity of a tissue in contact with a foreign body depends both on the tissue and on the foreign body's chemistry, surface, shape and size. It is, therefore, rather inaccurate to define a material “biocompatible”, since, in the vast majority of cases, such definition takes into account its chemistry and, to a lesser extent, its surface, but very seldom the shape that particular material takes when it is transformed into an implantable device or, in any case, into something that comes in contact with a living tissue, and even more rarely its size. In order to be biocompatible, a foreign body that is put in touch with a biological tissue must induce a specific protein adsorption from the extracellular matrix. There are many cellular processes, which are triggered by the type of protein adsorbed, by its conformation and by its biological activity. If the presence of a certain protein is requested to guarantee a proper interaction of the foreign body, generally, but not exclusively, an implantable medical device, with the biological environment, it may be possible to manipulate the implant surface in order to induce in advance that situation. The so-called “biomimetic” surfaces base their activity in the human body upon this concept. The ability to design such a system is greatly supported by biotechnologies and nanotechnologies. Medical applications of nanotechnologies are already available, for instance in dentistry, by the creation of nanocomposites for dental restorations.

At present, dental restorations employ amalgams, composites, or gold or ceramic inlays, but there is an urgent necessity to have more resistant materials, especially for posterior teeth where the mastication load is particularly high, capable of replacing the amalgam, long suspected to be toxic. Some dental materials employing nanoparticles, for instance of zirconia, are already available on the market, but other, more sophisticated, materials are being developed. Other emerging applications are those in the drug-delivery field and gene therapy. Those are made possible by the versatility of nanotechnologies and, particularly, by the extremely reduced size of those devices, similar to that of their targets. One of the most promising applications of nanoparticles is their use in pharmaceuticals as a drug-releasing support for neural diseases, capable of negotiating the blood-brain barrier. Nanosized materials can be the substrate where viruses or DNA molecules can be encapsulated or sorted.

The interaction of these biomolecules with the nanoparticle, nanotube or nanosized surface can serve to detect specific proteins or viruses and can guarantee the vehiculation of the molecules to the specific target. Nanospheres are already employed in humans, though only experimentally, in the diagnostic field. In fact, it was observed that highly lymphotrophic super-paramagnetic nanoparticles (monocrystalline iron oxide) can easily gain access to lymph-nodes by means of interstitial-lymphatic transport in patients suffering from prostate cancer. Their presence in lymph nodes can be detected by MRI (Magnetic Resonance Imaging) and their concentration can indicate a metastasis. But the possibility to interact with the smallest components of the human body is not much known and makes nanoparticles potentially dangerous, while verifying the results of this interaction is an awkward matter. It has already been demonstrated that those materials interact in different ways with the endothelium, macrophages and gut and liver epithelial cells. It was also discovered that metals are more dangerous than plastics for the survival activity of the cells. The production of the inflammatory and defence mediators depends on the particle chemistry. In-vitro tests suggest that some new phenomena can occur when the nanoscale range of interaction is investigated. From the clinical point of view, it has been known for a long time that inhaled particles can induce diseases like, for instance, asbestosis and silicosis. Another well-known clinical phenomenon is that a number of implantable medical devices wear in-vivo, thus creating debris of micro and nanosized particulate matter: an example of that is the wear of hip-joint prostheses and of dental restorations. The possibility that inorganic, chemically inert, microscopic debris can induce granulomatoses even in regions beyond the implant site is familiar to orthopaedic surgeons who must remove worn hip-joint prostheses because the debris their erosion produce brings about the local formation of granulomatous tissue and a bone degeneration with the ensuing loosening of the device.

The data we gathered induced us to think that a pathology can be started by the presence of inorganic particles that cannot be metabolised or, in any case, disposed of, and these findings have us strongly suspect that the size of the particles, their local concentration and their velocity to reach the critical concentration can have an influence on the type of pathology. As a consequence, the concept of biocompatibility should be revised, keeping into account the fact that a material, which is certainly accepted in bulk form, may be no longer biocompatible when its size is reduced below a certain “critical” threshold. Probably, also the different chemistry of the particles (either ceramic or metal or plastic materials) can influence the relationship between the cells and the material's surface, which can lead to a different cellular reaction and, as the next step, to a clinical expression, although no literature has ever considered this so far.