Hybrid Implants Based on Calcium-Magnesium Silicate Ceramic Diopside as a Carrier of Recombinant BMP-2 and Demineralized Bone Matrix as a Scaffold: Ectopic Osteogenesis in Intramuscular Implantation in Mice

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Anna S. Karyagina^1,2,3,a*, Polina A. Orlova¹, Anna V. Zhulina¹, Mikhail S. Krivozubov¹, Tatyana M. Grunina^1,3, Natalia V. Strukova¹, Kirill E. Nikitin¹, Vasily N. Manskikh^1,2, Fedor S. Senatov^1,4, and Alexander V. Gromov^1,b*

¹Gamaleya National Research Center of Epidemiology and Microbiology, Ministry of Healthcare of the Russian Federation, 123098 Moscow, Russia

²Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, 119992 Moscow, Russia

³All-Russia Research Institute of Agricultural Biotechnology, 127550 Moscow, Russia

⁴National University of Science and Technology “MISIS”, 119049 Moscow, Russia

^* To whom correspondence should be addressed.

Received June 14, 2023; Revised July 5, 2023; Accepted July 6, 2023

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High efficiency of hybrid implants based on calcium-magnesium silicate ceramic, diopside, as a carrier of recombinant BMP-2 and xenogenic demineralized bone matrix (DBM) as a scaffold for bone tissue regeneration was demonstrated previously using the model of critical size cranial defects in mice. In order to investigate the possibility of using these implants for growing autologous bone tissue using in vivo bioreactor principle in the patient’s own body, effectiveness of ectopic osteogenesis induced by them in intramuscular implantation in mice was studied. At the dose of 7 μg of BMP-2 per implant, dense agglomeration of cells, probably skeletal muscle satellite precursor cells, was observed one week after implantation with areas of intense chondrogenesis, initial stage of indirect osteogenesis, around the implants. After 12 weeks, a dense bone capsule of trabecular structure was formed covered with periosteum and mature bone marrow located in the spaces between the trabeculae. The capsule volume was about 8-10 times the volume of the original implant. There were practically no signs of inflammation and foreign body reaction. Microcomputed tomography data showed significant increase of the relative bone volume, number of trabeculae, and bone tissue density in the group of mice with BMP-2-containing implant in comparison with the group without BMP-2. Considering that DBM can be obtained in practically unlimited quantities with required size and shape, and that BMP-2 is obtained by synthesis in E. coli cells and is relatively inexpensive, further development of the in vivo bioreactor model based on the hybrid implants constructed from BMP-2, diopside, and xenogenic DBM seems promising.

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KEY WORDS: diopside, calcium-magnesium silicate ceramics, implant, BMP-2, demineralized bone matrix, ectopic osteogenesis

DOI: 10.1134/S0006297923080060

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