V.B. Akopyan1, V.N. Gorshenev2, E.S. Budoragin3, M.V. Bambura4, M.A. Dragun5

1,5 Bauman Moscow State Technical University (Moscow, Russia)

2 Institute of Biochemical Physics n. a. N.M. Emanuel of RAS (Moscow, Russia)

3 State Military Clinical Hospital n.a. N.N. Burdenko (Moscow, Russia)

4 Federal Institute of Industrial Property (FIIP) (Moscow, Russia)

Introduction reflects the great interest of practical restorative medicine in artificial structures that mimic the structure and properties of natural bone tissue that are made from biocompatible composite materials suitable for restoring the integrity of bone elements of the musculoskeletal system. The Introduction also contains the physicochemical foundations and approaches to a new ultrasonic technologies providing accelerated production of a biocompatible composite material, precisely hydroxyapatite particles in a collagen matrix.

Experimental part contains a description of methods and equipmets for accelerated production of a hydroxyapatite suspension in the field of a hydroacoustic emitter, which ensures that the cavitation threshold at room temperature is exceeded, at which intense acoustic vortex microflows provide a decrease in diffusion restrictions, accelerating the interaction between reacting components. The reaction is carried out with the simultaneous supply of an aqueous solution of calcium monophosphate hydrate and a suspension of calcium hydroxide. The resulting finished product is separated using an ultrasonic self-cleaning filter, where the same, by nature, microflows allow the implementation of a continuous accelerated separation of synthesized particles in an ultrasonic self-cleaning filter of the installation, where, after separation, the precipitate is also subjected to cleaning. The resulting particles of hydroxyapatite mixed with the solution collagen and homogenized in an ultrasonic field at frequency of 22 kHz and an energy density in the reaction volume from 1 to 10 W / cm3.

Obtained homogenate can be easily used to create various implant designs with predetermined sizes and shapes and after freezedrying was transformed in biocompatible composite with a porous structure. To control biocompatibility, samples of this composite in form of thin plate was sewed under the skin into the scruff of white lab rats.

A suspension of hydroxyapatite mechanically combined with the collagen during 30 s homogenization by ultrasound at frequency of 22 kHz and at energy density of 3 W / cm3, form a complex that is freeze-dried, after which it can be used to form the biocomposite body with porous structure and with given dimensions and shapes. Subcutaneous implantation of plates of a calcium-phosphate biocomposite with a biodegradable polymer collagen, into the scruff of a laboratory white mouse showed its good biocompatibility with tissues of a living organism, without causing either immediate or delayed adverse events in them. 

Akopyan V.B., Gorshenev V.N., Budoragin E.S., Bambura M.V., Dragun M.A. Synthesis of biocompatible calcium-phosphate compositions in ultrasound field. Biomedicine Radioengineering. 2021. V. 24. № 5. P. 59–79. DOI: 10.18127/j15604136-202105-07 (in Russian)

1. Ulery B.D., Nair L.S., Laurencin C.T. Biomedical applications of biodegradable polymers. Journal of polymer science Part B: polymer physics. 2011. V. 49. № 12. P. 832–864.
2. Patent № 2482880 (RF). Sposob polucheniya poristogo kostnogo biokompozita. V.N. Gor-shenyov, A.T. Teleshev, Yu.A. Ershov, G.Z. Kaziev, V.V. Kolesov, E.D. Sklyanchuk. 2012 (in Russian).
3. Patent № 2631594 (RF). Sposob polucheniya gidroksiapatit-kollagenovoj kompozicii. V.N. Gorshenyov, A.T. Teleshev, V.V. Kolesov, V.B. Akopyan, M.V. Bambura, E.S. Budoragin. 2017 (in Russian).
4. Patent № 1131553 (SU). Gidrodinamicheskij preobrazovatel'. V.G. Ponomaryov, V.F. Smirnov, R.G. Saruhanov, N.L. Smirnova. 1983 (in Russian).
5. Akopyan V.B., Ruhman A. A., Alenichev V.V., Gavrilov V. A. Intensifikaciya processov fil'-trovaniya. V kn. «Ul'trazvukovye tekhnologicheskie processy» Severodvinsk. 2000. S. 28–31 (in Russian).
6. Patent № 2342188 (RF) Sposob polucheniya emul'sij i suspenzij. V.B. Akopyan, A.A. Ruhman, E.R. Davidov, E.M. Mordvinova. 2007 (in Russian).
7. Margulis M.A., Akopyan V.B. Eksperimental'noe issledovanie zavisimosti skorosti zvuko-himicheskih reakcij i potoka sonolyuminescencii ot intensivnosti ul'trazvuka. Zhurnal fizi-cheskoj himii. 1978. T. 52. № 3. S. 601–605 (in Russian).
8. Patent № 2386111 (RF) Sposob ocenki raspredeleniya energii v ul'trazvukovom pole / V.B. Akopyan, A.A. Ruhman, N.E. Binyaev, B.I. Leonov, M.V. Bambura. 2008 (in Russian).
9. Akopyan V.B., Ershov Yu.A., Shchukin S.I. Osnovy vzaimodejstviya ul'trazvuka s biologicheski-mi ob"ektami. M.: YURAJT. 2020. 223 s. (in Russian).
10. Pat. № 2626355 (RF). Sposob smeshivaniya zhidkih sred. V.N. Gorshenyov, A.T. Teleshev, V.V. Kolesov, V.B. Akopyan, M.V. Bambura, M.L. Bogomolova, R.G. Saruhanov. 2017 (in Russian).