V.V. Rozanov - Ph.D. (Phys.-Math.), Dr.Sc. (Biol.), Professor, Department of Accelerators Physics and Radiation Medicine of Physical Faculty, Lomonosov Moscow State University; Leading Research Scientist of Scientific Centre of Hydro-Physics Researches; Head of Laboratory of All-Russian Scientific Research Institute of Medical and Aromatic Plants. E-mail: vro-zanov@mail.ru I.V. Matveychuk - Dr.Sc. (Biol.), Professor, Head of Scientific and Educational-Methodic Centre of Bio-Medical Technolo-gies of All-Russian Scientific Research Institute of Medical and Aromatic Plants. E-mail: nizbmtvilar@gmail.com Yu.I. Denisov-Nikol-sky - Academician of RAS, Dr.Sc. (Med.), Professor, Chief Research Scientist of Scientific and Edu-cational-Methodic Centre of Bio-Medical Technologies of All-Russian Scientific Research Institute of Medical and Aromatic Plants. E-mail: nizbmtvilar@gmail.com Yu.Yu. Litvinov - Deputy Head of Scientific and Educational-Methodic Centre of Bio-Medical Technologies of All-Russian Scientific Research Institute of Medical and Aromatic Plants. E-mail: nizbmtvilar@gmail.com

The characteristics of the structural organization of natural composite - bone tissue of humans and animals (ox, pig) as the object of biotechnology research and development of interest to bioimplantology are discussed. Modern innovative methods of sample preparation, allowing to manufacture bone implants of different shapes, sizes, composite structure based biological and methodological factors are presented. In particular, an effective separation of bone tissue for manufacturing of standard cylindrical specimens with different orientations relative to the longitudinal axis of the bone is possible by using hollow cylindrical cutters with different lengths and diameters, cutting milling cutters up to 150 microns thick with a toothed cutting part or made using diamond deposition, as well as special assistive devices and adaptations. The resulting samples are very convenient to carry out mechanical tests according to standard conventional techniques. Another innovative solution proposed for sample preparation is the use of hydro-jet technology that can not only effectively cut bone fragments with different compositional structure, but also provide an opportunity to give them the desired shape while achieving high-quality machined surfaces. As a result, thanks to the author\'s development of high-tech methods of physical-mechanical separation and processing of bone fragments we have the opportunity to minimize damage of the sur-face layer of the implants and to ensure its compliance with the bioimplantology requirements. A detailed study have been performed to investigate the features of intraosseous spaces (IOS) system, which is formed at various stages of osteogenesis and is a multi-level volumetrical oriented system of the central, perforating (anastomosing) channels, gaps and tubules, interfibrillary and intercrystalline spaces . This complex spatial configuration allows the use of bone tissue as a depot for the creation of new pharmaceuticals, in which the bone plays the role of carrier for drugs targeted delivery into the surgical intervention zone. The advanced methods are proposed for sterilization of bone fragments in all stages of the process of their production, which ensures not only the safety of the patients, but also reliable protection of personnel as well as eliminate the harmful effects on the environment.

 

1. Denisov-Nikolskijj JU.I., Mironov S.P., Omeljanenko N.P., Matvejjchuk I.V. Aktualnye problemy teoreticheskojj i klinicheskojj osteoartrologii. M.:OAO «Tipografija «Novosti». 2005. 336 s.
2. Lavrishheva G.I., Onoprienko G.A. Morfologicheskie i klinicheskie aspekty reparativnojj regeneracii opornykh organov i tkanejj. M.: Medicina. 1996. 208 s.
3. Matvejjchuk I.V.,Rozanov V.V., Litvinov JU.JU., Andreeva T.M. Biotekhnologicheskie podkhody k optimizacii kachestva implantatov dlja kostnojj plastiki // Materialy 2-go Nacionalnogo Kongressa po regenerativnojj medicine. M.: MEDI. 2015. S. 106.
4. Denisov-Nikolskijj JU.I., Matvejjchuk I.V.,Rozanov V.V.Innovacionnye podkhody k strukturno-funkcionalnomu analizu kostnojj tkani dlja reshenija fundamentalnykh i prikladnykh zadach v bioimplantologii i biomaterialovedenii // Voprosy biologicheskojj, medicinskojj i farmacevticheskojj khimii. 2012. № 1.S. 223-228.
5. Matvejjchuk I.V.,Rozanov V.V.,Denisov-Nikol­skijj JU.I.Sravnitelnaja strukturno-funk­cionalnaja kharakteristika kostnykh allo- i ksenoimplantatov // Tekhnologii zhivykh sistem. 2013. T.10. № 8. S. 25-30.
6. Rozanov V.V.Vysokoehnergeticheskoe gidrodinamicheskoe vozdejjstvie na biologicheskie tkani - novaja perspektivnaja biomedicinskaja tekhnologija// Naukoemkie tekhnologii. 2003. № 6. S. 35-43.
7. Rozanov V.V., Denisov-Nikolskijj JU.I., Matvejjchuk I.V., Lozhkin O.V., EHjjkhenvald EH.V., Osipenkova T.K., Omeljanenko N.P., Seve- rin A.E. Gidrodinamicheskie tekhnologii v biologii i medicine // Tekhnologii zhivykh sistem. 2005. T. 2. № 4-5. S. 28.
8. Polimery medicinskogo naznachenija / Pod red. prof. Sehnoo Manabu. M.: Medicina. 1981. 248 s.
9. Matvejjchuk I.V. Izuchenie sistemy vnutrikostnykh prostranstv s pozicijj biomaterialovedenija i ego prikladnoe znachenie  Sb. nauchn. tr. NIC BMT VILAR «Biomedicinskie tekhnologii». M.1998. Vyp. 9. S. 54-58.
10. Bogonatov B.N., Gonchar-Zaikina N.G. Sistema  kostnykh kanalov kak osnova angioarkhitektoniki kostejj // Arkhiv AGEH. 1976. № 4. S. 53-61.
11. Denisov-Nikolskijj JU.I., Doktorov A.A. Prostranstvennaja organizacija lakunarno-kanal­cevojj sistemy v strukturakh plastinchatojj kosti // Arkhiv AGEH. 1987. № 8. S. 37-43.
12. Modjaev V.P., Utenkin A.A., Sveshnikova A.A., Karpova A.A. Kolichestvennye kharakteristiki struktury kompaktnogo veshhestva kosti // Arkhiv AGEH. 1973. T. 64. № 5. S. 69-72.
13. Omeljanenko N.P., Butyrin G.M. Kolichestvennyjj analiz mezhstrukturnogo prostranstva kompaktnogo veshhestva kosti cheloveka // Vestnik travmatologii i ortopedii im. N.N. Priorova. 1994. № 1. S. 51-54.
14. Lunkov A.E. Porometricheskie metodiki morfometrii kostnojj tkani. Saratov: Izd-vo Saratovskogo medicinskogo universiteta. 2015.120 s.
15. Lunkov A.E., Abrosimov G.N. Metod opredelenija sostava kostnojj tkani // Arkhiv AGEH. 1991. № 2. S. 88-91.
16. Panteleev V.I.,Rozanov V.V.,Matvejjchuk I.V.,Lekishvili M.V.,Sysoev N.N.,SHuteev S.A.,Alkov S.V., Andreeva T.M.Medicinskie ozonovye tekhnologii. Novye zadachi, vozmozhnosti, oborudovanie // Biomedicinskaja radioehlektronika. 2013. № 2. S. 3-11.
17. Patent №2526429 (RF). Sposob izgotovlenija kostnykh implantatov. / V.A. Bykov, V.V.Rozanov, I.V. Matvejjchuk,V.I. Panteleev, S.A.SHu­teev, JU.JU. Litvinov, A.I.Vorotnikov.
18. Rozanov V.V.,Matvejjchuk I.V.,Lekishvili M.V.,Litvinov JU.JU., Andreeva T.M.,Nikolaeva A.A.Innovacionnye podkhody k sterilizacii kostnykh implantatov // Tekhnologii zhivykh sistem. 2015. T.12. № 4. S. 59-61.
19. Matvejjchuk I.V.,Rozanov V.V.,Panteleev V.I.,Agalakova L.M.,Kirilova I.A.Innovacionnye podkhody k sovershenstvovaniju processa sterilizacii dlja reshenija zadach bioimplantologii // Voprosy biologicheskojj, medicinskojj i farmacevticheskojj khimii. 2013. № 11. S. 92-98.
20. Sibeldina L.A. Sterilizacija ozonom // Medicina i zdorove. 2007. № 11(19). S. 24-25.
21. Savelev V.I. Opyt zagotovki i primenenija demineralizovannykh kostnykh transplantatov// V kn.: Transplantacija demineralizovannojj kostnojj tkani pri patologii oporno-dvigatelnojj sistemy. L., 1990. S. 4-22.
22. Kakiuchi M., Ono K. Defatted, gas-sterilised cortical bone allografts for posterior lumbar interbody vertebral fusion // Int. Orthopaed. 1998.  V. 22. № 2.P. 69-76.
23. Jackson D.W., Windler G., Simon T.M. Intra­articular reaction associated with the use of freeze-dried, ethylene oxide-sterilized bone-patellar tendon-bone allografts in the reconstruction of the anterior cruciate ligament // Am. J. Sports Med. 1990. V.18. №1. P. 1-10.
24. Tshamala M., Cox E., De Cock H., et al. Antigenicity of cortical bone allografts in dogs and effect of ethylene oxide-sterilization // Vet Immunol. Immu­nopathol. 1999. V. 69. № 1. P. 47-59.
25. Thorén K., Aspenberg P. Ethylene oxide steri­lization impairs allograft incorporation in a con­duction chamber // Clin. Orthop. 1995. № 318. P. 259-264.
26. Russell J.L., Block J.E. Clinical utility of demineralized bone matrix for osseous defects, arthodesis, and reconstruction: impact of proc­essing techniques and study methogology // Orthopedics. 1999. V. 22. № 5. P. 524-531.
27. Danielson N.E. The use of ethylene oxide in the hospital setting // Sterilization of medical products. Johnson&Johnson. 1991. P. 194-2.
28. Ratent № 5 (USA). Method of sterilization of bone tussue / J.P. Dalmasso, T.J.Mielnik.
29. SHevcov V.I., Desjatnichenko K.S., Ustjuzhanina O.B., Djachkov A.N., Larionov A.A., Luneva S.N., Grebneva O.L., Izotova S.P., Makhnina N.K., Alieva S.I., Fadeeva O.N. Konstruirovanie i ehksperimentalnaja aprobacija farmpreparatov iz zrelojj kostnojj tkani // Genijj ortopedii. 1996. № 4. S. 6-12.
30. Rebrova G.A., Denisov-Nikolskijj JU.I., Vasilevskijj V.K., Doktorov A.A., Matvejjchuk I.V., Sinkova M.M. Primenenie kollagensoderzhashhikh biopolimerov v kachestve nositelejj lekarstvennykh preparatov // Biomedicinskie tekhnologii  Sb. nauchn. tr. NIC BMT VILAR. M. 1996. Vyp. 3. S. 48-57.
31. Sosina I.N. Fizioterapevticheskijj spravochnik. Kiev. 1967. S. 5-30.
32. Patent № 606584 (RU). Sposob nasyshhenija  kostnykh transplantatov medikamentami. / V.M. Krivenko, P.A. Skripnjuk, I.V. SHumada.
33. Patent  №235035733 (RF). Sposob fiksacii lekarstvennykh sredstv na nositele. / I.A. Kirilova.
34. Lekishvili M.V.,Skljanchuk E.D., Akatov V.S., Ochkurenko A.A.,Gurev V.V., Rozanov V.V.,Matvejjchuk I.V.,CHekanov A.V., Rjabov A.JU., Fadeeva I.S., JUrasova JU.B.Kooperacija nauchnykh centrov s celju razrabotki novykh kostno-plas­ticheskikh materialov dlja travmatologii i ortopedii // Tekhnologii zhivykh sistem. 2015. T. 12. № 4. S. 52-54.