Bricks, tiles, bathroom equipment and kitchenware, fancy items of porcelain and earthenware, terra cotta and majolica, piezoelectric and ferroelectric articles-such is the far-from -complete list of applications of ceramics. Another, and very important sphere of its application, deserving of special mention, is medicine. Today one often reads and hears about new uses of these remarkable materials in dentistry, maxillofacial surgery and orthopedics. But what is really surprising in this respect is that such alien material can be made "part and parcel" of the human body. In the article that follows Arkady Maltsev of our staff discusses the problem of what specialists call biocompatible materials, their origin and current applications, with two leading experts in the field-Academician Vladimir Shevchenko, Director of the RAS Institute of Chemistry of Silicates (named after I. Grebenshchikov), and Academician Pavel Sarkisov, Rector of the Russian Chemico-Technological University (named after Mendeleyev).
- The first steps towards broad medical uses of biocompatible materials were made in this and other countries rather recently. But how it all started?
Shevchenko: From the mid-1970s specialists in economically developed countries embarked upon a search for new materials which, they believed, could cause radical improvements in the development of dentistry and surgery. The basic element in this process was calcium hydroxyapatite Са 10 (PO 4 ) 6 (OH) 2 . Being what we call a structural analog of the mineral component of bone tissue, it has the same chemical composition and is biologically compatible. What is more, it can stimulate the regeneration of damaged bones, preventing their inflammation or rejection. Considerable allocations are provided in certain countries for the development of such materials on the basis of calcium, and the cost of these materials is very high. Thus one gram of hydroxyapatite costs from 10 to 100 US dollars depending on the grade of the product. In our
own country research in this field did not receive federal financial backing for quite a while, being conducted on what one could call a personal and sporadic basis which was reflected in delays with obtaining tangible results. There was a threat of our lagging behind with these innovations which are so important for medicine. And medical experts were eagerly awaiting them for rapid rehabilitation of invalids, for more effective methods of treatment of bone pathologies and significant improvements in dentistry and surgery.
- So what was done to improve the situation?
Sarkisov: Changes for the better took place in the late 1980s-early 1990s. Serious studies were initiated at that time into improved production technologies of calcium hydroxyapatite and its medical uses. The success was predetermined by a considerable backlog of scientific and technical achievements and the involvement of top-notch researchers from the academic institutes of General and Inorganic Chemistry (named after Kurnakov) and of the Physico-Chemical Problems of Ceramic Materials as well as of the Russian Chemico-Technological University (named after Mendeleyev) and other centers. But the achievement of our ultimate objective - the development and production of effective biocompatible materials-called for the pooling together of all of our intellectual and financial resources. With this aim in view a special R&D center, or structure, was established (POLISTOM), which pooled together the brains and experience of scientists and specialists in various fields-chemists, physicists, pharmacists, physiologists, technologists and medics-and this ensured tangible results. Within a relatively short span of time they developed the basics of the industrial synthesis of hydroxyapatite and other biocompatible calcium phosphates. Multi-component (composite) products were developed and comprehensive biochemical and medico-biological studies of all the new materials were conducted, followed by the launching of their commercial production. Involved on the project were experts from many institutes and medical centers including, in addition to the ones mentioned before, the Moscow Medical Academy (named after Sechenov), the Moscow State Medical Sto-
matological University, the Central Scientific Research Institute of Stomatology, etc. The quality of the new materials received top assessments and they were cleared for clinical uses. All the property rights involved have been protected by the appropriate patents. And one can add to the above that our "know-hows" differ from foreign analog by their relative simplicity and lower costs.
- And what is the price of this Russian product now?
Shevchenko: The price is not very high: one gram of the powder (brand name HYDROXYAPOL) produced by the POLIST Plant costs about one US dollar. Thus the prices are really incomparable.
- What else has been done in this country in this field?
Shevchenko: We have achieved world-level results in our fundamental and applied studies. Let me cite a few examples. Take, for instance, the processes of isomorphic replacement which has a key role to play in the vital processes in bone tissue. What we call a structural-thermochemical model has been developed by a team of experts headed by Dr. Vladimir Orlovsky at the RAS Institute of General and Inorganic Chemistry (named after Kurnakov). With the help of this model specialists have studied the energetics of the isomorphous replacement of hydroxyl (OH) with halogenes in the calcium channels of the structure of hydroxyapatite. This made it possible to formulate a hypothesis of the biological process occurring in human bone tissue with a synergetic (combined) participation of ions of hydroxyl, fluorine and carbonate ions.
Another major problem consists in understanding the interaction between the mineral (hydroxyapatite) and organic (collagen, polysaccharides) constituents of bone tissue, since it represents a composite material with a complex array of the aforesaid components. In this connection preparations like KOLAPOL, GAPKOL and PARODONKOL represent a significant step forward in the sphere of bone regeneration.
The human body possesses cortical (high-density) and spongy (highly porous) bone tissues. Our specialists proposed a technique of producing dense and porous ceramics on the basis of hydroxyapatite and intended for implantations respectively into cortical and spongy bones. A team headed by Dr. Sergei Barinov developed an original method of manufacture of ceramics with sub- micropores and pores measuring several hundreds of micrometers. The former are necessary for improving the adsorption of blood proteins proceeding the adhesion and the multiplication of osteogenic cells, and the latter serve as channels for "biological flows" which are necessary for the adhesion of an implant to the live bone tissue.
One version of such ceramic products are high-porosity granules developed by our specialists. They can be used for what we call localized (targeted) and prolonged transport of medicinal preparations directly into the organ submitted to therapy. This method of drugs administration offers important advantages as compared with peroral or intravenous methods, especially when blood flow is upset because of traumas of blood vessels.
Sarkisov: An important class of bioactive products are glasses and glassy-crystalline materials containing calcium phosphates. Studies conducted at our university have revealed the principles of controlling the bioactivity of these materials, specified the role of their structure, chemical properties and surface phenomena in the processes of biointegration with living tissues. Dense and porous materials developed by our experts, including those with differentiated porosity (external and internal) and regulated resorbtion capacity in the body can be used both as "monoliths" and as coatings of titanium implants. The metal sustains the main mechanical stress, or load, and the coating ensures the biocompatibility of the whole structure. Recently there appeared glassy-crystalline fillers for dental filling materials.
- In the treatment of certain disorders today composite materials are in high demand. What is the reason for that?
Sarkisov: This is, first of all, because they have been developed on the basis of hydroxyapatite with collagen. The latter plays an active binding role, making it possible to manufacture articles in the form of porous plates, sponges, films, membranes and granules. Their properties vary within a broad range. Say, sponges with hydroxyapatite contents of up to 25 percent can be used to stop hemorrhages even in cases of hemophilia. Articles with a higher levels of hydroxyapatite are used in traumatology and dentistry as an osteoplastic composite for stimulating bone tissue formation in cases of its defects or lesions.
Materials available for therapies of infected bone lesions include antibacterial preparations - LIN- COMYCIN and METRONIDA-ZOL or their combinations. Being gradually released during resorption, they suppress microbial activity while at the same time accelerating bone tissue regeneration. Used in dentistry now are special PARADANKOL membranes for treatment of paradontosis. The "menu" of currently available composite materials includes 18 items.
Shevchenko: And let me stress once again that all of the aforesaid innovations are the fruits of tremendous efforts of our scientists, such as the Corresponding Member of the Russian Academy of Medical Sciences, Valery Leontyev. On the basis of a thorough biochemical analysis of saliva, dental and bone tissues he explained for the first time the processes of their regeneration and mineralization, identified the key role of hydroxiapatite in the vital functions of the human organism. A tremendous contribution to the "birth" of this chemical compound was provided by Dr. V. Orlovsky. Dr. L. Istranov and Candidate of Technical Sciences, S. Kurdyumov, suggested the concept of developing composite materials on the basis of phosphates of calcium and collagen, and Dr. A. Volozhinin studied their interaction with body cells and tissues. Both of them headed big teams of researchers conducting priority studies of world importance. But the really main thing is that thanks to the combined efforts of researchers and production specialists we now have at our disposal powders, granules, spongy and composite materials which are no inferior, and often better than their foreign analogs. Using them our medical specialists now perform tens of thousands of operations a year in more than 150 cities of Russia.