The current state and promising innovative directions to development methods for bioimplant sterilization

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We have analyzed the state-of-the-art methods for sterilization of bone implants. The problem of finding effective bioimplant sterilization methods is still far from its optimal solution and remains as urgent as before. The factors limiting further development of the main biomaterial sterilization methods include limitations related to each existing method and the use of technologies with sterilizing effect. Comparative analysis of the main techniques for bioimplant sterilization that are used in medical and biological areas (treatment with ethylene oxide, radiation, wet warmth, liquid media, and ozone) allows for a conclusion on the advantages of the radiation sterilization. However, the choice is challenged by the dilemma: higher radiation dose would increase the sterilization effect, but at the same time can lead to multiple morphological abnormalities in the tissues, deterioration of their mechanical characteristics, destruction of morphogenetic proteins and consequently to lower efficacy of the reparative bone formation. As a  result, the material can become unsuitable for clinical use. One of the real approaches to solve this problem is to use as low absorbed radiation dose as possible during irradiation of biomaterials, at least to 15 kGy. The developments made by the authors within the last years have shown that such a  result can be achieved by the use of combines sterilization techniques based on combines effects of a  number of physical and chemical factors on the biomaterial being sterilized. Mutual enhancement of the sterilizing effects of these factors creates prerequisites for their synergy, whereby the intensity of each factor can be reduced. This makes it possible to decrease the degree of harmful adverse events associated with each individual factor with higher total effect. The search for innovative solutions for the urgent problems of the bone bioimplant sterilization, for the development of the state-of-the-art health-sparing technologies can be successful only with unification of the efforts by specialists from related sciences. This would allow for creating of breakthrough technologies for sterilization and for optimization of this procedure with achievement of its high efficacy.

About the authors

V. V. Rozanov

Lomonosov Moscow State University; All-Russian Scientific Research Institute of Medicinal and Aromatic Plants

Author for correspondence.
ORCID iD: 0000-0002-3243-8782

Vladimir V. Rozanov - PhD (in Phys. and Math.), Doctor of Biol. Sci., Associate Professor, Leading Research Fellow of Scientific Centre of Hydro-physics Researches, Professor of the Chair of Accelerators Physics and Radiation Medicine, Faculty of Physics Lomonosov MSU; Head of Laboratory, Scientific and Educational-methodic Centre of Bio-medical Technologies All-Russian Scientific RIMAP, ResearcherID: E-5959-2017

1/2 Leninskie gory, Moscow, 119991, tel.: +7 (495) 939 13 44

Russian Federation

I. V. Matveychuk

All-Russian Scientific Research Institute of Medicinal and Aromatic Plants

ORCID iD: 0000-0001-6220-4429

Igor V. Matveychuk - Doctor of Biol. Sci., Professor, Head of Scientific and Educational-methodic Centre of Bio-medical Technologies; ResearcherID: AAE-8495-2019.

2 Krasina ul., Moscow, 123056, Tel.: +7 (499) 254 46 49

Russian Federation


  1. Nemzek JA, Arnoczky SP, Swenson CL. Retroviral transmission in bone allotransplantation. The effects of tissue processing. Clin Orthop Relat Res. 1996;(324):275–82.
  2. Marthy S, Richter M. Human immunodeficiency virus activity in rib allografts. J Oral Maxillofac Surg. 1998;56(4):474–6. doi: 10.1016/s0278-2391(98)90716-9.
  3. Martinez OV, Buck BE, Hernandez M, Malinin T. Blood and marrow cultures as indicators of bone contamination in cadaver donors. Clin Orthop Relat Res. 2003;(409):317–24. doi: 10.1097/01.blo.0000053343.97749.21.
  4. Singh R, Singh D, Singh A. Radiation sterilization of tissue allografts: A review. World J Radiol. 2016;8(4):355–69. doi: 10.4329/wjr.v8.i4.355.
  5. Пантелеев ВИ, Розанов ВВ, Матвейчук ИВ, Лекишвили МВ, Сысоев НН, Шутеев СА, Альков СВ, Андреева ТМ. Медицинские озоновые технологии. Новые задачи, возможности, оборудование. Биомедицинская радиоэлектроника. 2013;(2):3–11.
  6. Матвейчук ИВ, Розанов ВВ, Пантелеев ВИ, Агалакова ЛМ, Кирилова ИА. Инновационные подходы к совершенствованию процесса стерилизации для решения задач биоимплантологии. Вопросы биологической, медицинской и фармацевтической химии. 2013;(11):92–8.
  7. Алимов АС, Близнюк УА, Борщеговская ПЮ, Варзарь СМ, Еланский СН, Ишханов БС, Литвинов ЮЮ, Матвейчук ИВ, Николаева АА, Розанов ВВ, Студеникин ФР, Черняев АП, Шведунов ВИ, Юров ДС. Применение пучков ускоренных электронов для радиационной обработки продуктов питания и биоматериалов. Известия Российской академии наук. Серия физическая. 2017;81(6):819–23.
  8. Розанов ВВ, Матвейчук ИВ, Лекишвили МВ, Литвинов ЮЮ, Андреева ТМ, Николаева АА. Инновационные подходы к стерилизации костных имплантатов. Технологии живых систем. 2015;12(4):74–6.
  9. Aho AJ, Hirn M, Aro HT, Heikkilä JT, Meurman O. Bone bank service in Finland. Experience of bacteriologic, serologic and clinical results of the Turku Bone Bank 1972-1995. Acta Orthop Scand. 1998;69(6):559–65. doi: 10.3109/17453679808999255.
  10. Czapliński J. Sterilisation with ethylene oxide – economics and safety. Forum Zakażeń. 2014;5(4):235–7. doi:
  11. Kearney JN, Bojar R, Holland KT. Ethylene oxide sterilisation of allogenic bone implants. Clin Mater. 1993;12(3):129–35. doi: 10.1016/0267-6605(93)90063-d.
  12. Kakiuchi M, Ono K. Preparation of bank bone using defatting, freeze-drying and sterilisation with ethylene oxide gas. Part 2. Clinical evaluation of its efficacy and safety. Int Orthop. 1996;20(3):147–52. doi: 10.1007/s002640050052.
  13. Kakiuchi M, Ono K, Nishimura A, Shiokawa H. Preparation of bank bone using defatting, freeze-drying and sterilisation with ethylene oxide gas. Part 1. Experimental evaluation of its efficacy and safety. Int Orthop. 1996;20(3): 142–6. doi: 10.1007/s002640050051.
  14. Arizono T, Iwamoto Y, Okuyama K, Sugioka Y. Ethylene oxide sterilization of bone grafts. Residual gas concentration and fibroblast toxicity. Acta Orthop Scand. 1994;65(6):640–2. doi: 10.3109/17453679408994621.
  15. Muscarella LF. Use of ethylene-oxide gas sterilisation to terminate multidrug-resistant bacterial outbreaks linked to duodenoscopes. BMJ Open Gastroenterol. 2019;6(1):e000282. doi: 10.1136/bmjgast-2019-000282.
  16. Tshamala M, Cox E, De Cock H, Goddeeris BM, Mattheeuws D. Antigenicity of cortical bone allografts in dogs and effect of ethylene oxide-sterilization. Vet Immunol Immunopathol. 1999;69(1):47–59. doi: 10.1016/s0165-2427(99)00042-2.
  17. Russell JL, Block JE. Clinical utility of demineralized bone matrix for osseous defects, arthrodesis, and reconstruction: impact of processing techniques and study methodology. Orthopedics. 1999;22(5):524–31.
  18. Dziedzic-Goclawska A. The effect of radiation sterilization on connective tissue allografts. Proceedings of 2nd World Congress on Tissue Banking “Allograft against disability”. Warsaw; 1999. p. 48.
  19. Tallentire A. The spectrum of microbial radiation sensitivity. Radiation Physics and Chemistry. 1977;15(1):83–9. doi: 10.1016/0146-5724(80)90101-6.
  20. Schmidt T, Hoburg A, Broziat C, Smith MD, Gohs U, Pruss A, Scheffler S. Sterilization with electron beam irradiation influences the biomechanical properties and the early remodeling of tendon allografts for reconstruction of the anterior cruciate ligament (ACL). Cell Tissue Bank. 2012;13(3):387–400. doi: 10.1007/s10561-011-9289-6.
  21. Розанов ВВ, Матвейчук ИВ, Черняев АП, Николаева НА. Изменения морфомеханических характеристик костных имплантатов при радиационной стерилизации. Известия Российской академии наук. Серия физическая. 2019;83(10):1435–40. doi: 10.1134/S0367676519040203.
  22. Осипенкова-Вичтомова ТК. Судебно-медицинская экспертиза костей. М.: Бином; 2017. 272 с.
  23. Шангина ОР, Нигматуллин РТ. Влияние радиационной стерилизации на структуру и свойства биоматериалов. Морфология. 2006;129(3):44–7.
  24. Nguyen H, Cassady AI, Bennett MB, Gineyts E, Wu A, Morgan DA, Forwood MR. Reducing the radiation sterilization dose improves mechanical and biological quality while retaining sterility assurance levels of bone allografts. Bone. 2013;57(1):194–200. doi: 10.1016/j.bone.2013.07.036.
  25. Akkus O, Belaney RM. Sterilization by gamma radiation impairs the tensile fatigue life of cortical bone by two orders of magnitude. J Orthop Res. 2005;23(5):1054–8. doi: 10.1016/j.orthres.2005.03.003.
  26. Nguyen H, Morgan DA, Forwood MR. Validation of 11 kGy as a radiation sterilization dose for frozen bone allografts. J Arthroplasty. 2011;26(2):303–8. doi: 10.1016/j.arth.2010.03.032.
  27. Draenert GF, Delius M. The mechanically stable steam sterilization of bone grafts. Biomaterials. 2007;28(8):1531–8. doi: 10.1016/j.biomaterials.2006.11.029.
  28. Le Huec JC. Experimental study of the thermic effect on bone at 60 degrees C, as applied to bone allograft. Chirurgie. 1992;118(6–7):397– 404. French.
  29. Kühne JH, Refior HJ, Jansson V, DeToma G, Liepold KP, Verpoorten U. Initial clinical results with heat-treated homologous bone transplants. Z Orthop Ihre Grenzgeb. 1994;132(2): 102–11. German. doi: 10.1055/s-2008-1039827.
  30. Rauh J, Despang F, Baas J, Liebers C, Pruss A, Gelinsky M, Günther KP, Stiehler M. Comparative biomechanical and microstructural analysis of native versus peracetic acid-ethanol treated cancellous bone graft. Biomed Res Int. 2014;2014:784702. doi: 10.1155/2014/784702.
  31. Сибельдина ЛА. Стерилизация озоном. Медицина и здоровье. 2007;11(19):24–5.
  32. Сибельдина ЛА. Дезинфектанты: защита или угроза? Медицина и здоровье. 2009;9(41): 28–9.
  33. Быков ВА, Розанов ВВ, Матвейчук ИВ, Пантелеев ВИ, Шутеев СА, Литвинов ЮЮ, Воротников АИ, авторы; ГНУ ВИЛАР Россельхозакадемии, патентообладатель. Способ изготовления костных имплантов. Пат. 2526429 Рос. Федерация. Опубл. 20.08.2014.
  34. Пантелеев ИВ, Розанов ВВ, Матвейчук ИВ, Бахтин НА, Журнаков ЕА, Сидельников НИ, авторы; ФГБНУ ВИЛАР, патентообладатель. Установка для стерилизации биоматериалов. Пат. 180532 Рос. Федерация. Опубл. 15.06.2018.
  35. Nather A, Chew JLL, Aziz Z. Types of Terminal Sterilization of Tissue Grafts. In: Nather A, Yusof N, Hilmy N. Radiation in Tissue Banking. World Scientific; 2007. p. 3–9. doi: 10.1142/9789812708649_0001.
  36. Dalmasso JP, Mielnik TJ, inventors; Steris Corp, assignee. Method of sterilization of bone tissue. United States patent 5788941A. 1998 Apr 8.
  37. Савельев ВИ, Булатов АА, Рыков ЮА, авторы; ФГУ «РНИИТО им. Р.Р. Вредена Росмедтехнологи», патентообладатель. Комбинированный способ стерилизации костных трансплантатов. Пат. 2356224 Рос. Федерация. Опубл. 27.05.2009.
  38. Эйдус ЛХ. Мембранный механизм биологического действия малых доз. М.; 2001.
  39. Матвейчук ИВ, Розанов ВВ, Гордонова ИК, Никитина ЗК, Сидельников НИ, Литвинов ЮЮ, Николаева АА, Черняев АП, Пантелеев ИВ, авторы; ФГБНУ ВИЛАР, патентообладатель. Комбинированный способ стерилизации костных имплантатов. Пат. 2630464 Рос. Федерация. Опубл. 08.09.2017.

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Copyright (c) 2019 Rozanov V.V., Matveychuk I.V.

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