Biotechnological aspects of the working-out and manufacturing of living bone equivalent

Authors

DOI:

https://doi.org/10.15674/0030-59872023487-92

Keywords:

Regenerative medicine, bone defects, living bone equivalent, human cell-based medicinal products, multipotent mesenchymal stromal/stem cells

Abstract

Objective. To handle biotechnological aspects in manufacturing processes of three-dimensional living bone equivalent for restoration of critical sized bone defects for innovative treatment of combat-related casualties. Methods. To fabricate living bone equivalent we used devitalized xenogeneic bone scaffolds (DBM chips) and autologous fibrin hydrogel seeded with autologous cultured bone marrow-derived multipotent mesenchymal stem/stromal cells (BM-MSCs). Quality/identity control of cell cultures was assured by donor and cell culture infection screening (IFA, PCR), flow cytometry (cell phenotype), karyotyping (GTG banding), functional assays (CFU assay, multilineage differentiation assay). Results. The BM-MSC cultures had a normal karyotype and appropriate phenotype, multilinear differentiation potential and functional properties, appropriate CFU frequency and hadn’t any signs of cell senescence. The FDA/PI combined staining showed the demineralized bone chips’ regular seeding with viable cells. Conclusions. An actual regenerative medicine approach to organ-saving transplantation of the three-dimensional living bone equivalent for combat-related casualties requires further preclinical and clinical approbation for thorough studies on the bone integrity restoration, forming new bone tissue in a site of bone defect, and duration of rehabilitation period compared to the gold standard of the conventional bone defect cure.

Author Biographies

Dmytro Zubov, SI «Institute of Traumatology and Orthopaedics of the NAMS of Ukraine», Kyiv

SI «NSC «M. D. Strazhesko Institute for Cardiology, Clinical & Regenerative Medicine NAMS of Ukraine», Kyiv
«Medical & Diagnostic Centre «Profimed» LLC, ADONIS Medical Group of Companies, Kyiv. Ukraine

PhD in Biol. Sci.

Iurii Poliachenko, SI «Institute of Traumatology and Orthopaedics of the NAMS of Ukraine», Kyiv

MD, Dr. Sci. in Medicine, Prof.

Oleksandr Kostrub, SI «Institute of Traumatology and Orthopaedics of the NAMS of Ukraine», Kyiv

MD, Dr. Sci. in Medicine, Prof.

Roman Blonskyi, SI «Institute of Traumatology and Orthopaedics of the NAMS of Ukraine», Kyiv

MD, Dr. Sci. in Medicine

Oleksandr Magomedov, SI «Institute of Traumatology and Orthopaedics of the NAMS of Ukraine», Kyiv

MD, Dr. Sci. in Medicine, Prof.

Oleksii Dolgopolov, SI «Institute of Traumatology and Orthopaedics of the NAMS of Ukraine», Kyiv

MD, Dr. Sci. in Medicine

Ivan Zasadnyuk, SI «Institute of Traumatology and Orthopaedics of the NAMS of Ukraine», Kyiv

MD, PhD in Medicine

References

  1. Marx, R. E., Carlson, E. R., Eichstaedt, R. M., Schimmele, S. R., Strauss,J. E., & Georgeff, K. R. (1998). Platelet-rich plasma: Growth factor enhancement for bone grafts. Oral Surgery, Oral Medicine, Oral Pathology, Oral Radiology, and Endodontology, 85 (6), 638–646. https://doi.org/10.1016/s1079-2104(98)90029-4
  2. Urist, M. R. (1965). Bone: formation by autoinduction. Science, 150 (3698), 893–899. https://doi.org/10.1126/science.150.3698.893
  3. Johnson, E. E., Urist, M. R., & Finerman, G. A. (1988). Bone morphogenetic protein augmentation grafting of resistant femoral nonunions. A preliminary report. Clinical orthopaedics and related research, (230), 257–265.
  4. Phemister, D. B. (1947). Treatment of ununited fractures by onlay bone grafts without screw or tie fixation and without breaking down of the fibrous union. J Bone Joint Surg Am., 29 (4), 946–960.
  5. Burwell, R. G. (1964). Studies in the transplantation of bone. VII. The fresh composite homograft-autograft of cancellous bone: an analysis of factors leading to osteogenesis in marrow transplants and in marrow-containing bone grafts. J Bone Joint Surg Br., 46 (1), 110–140.
  6. Connolly, J. F. (1998). Clinical use of marrow osteoprogenitor cells to stimulate osteogenesis. Clinical orthopaedics and related research (1976-2007), 355, S257–S266. https://doi.org/10.1097/00003086-199810001-00026
  7. Muschler, G. F., Nitto, H., Matsukura, Y., Boehm, C., Valdevit, A., Kambic, H., Davros, W., Powell, K., & Easley, K. (2003). Spine fusion using cell matrix composites enriched in bone marrow-derived cells. Clinical orthopaedics and related research, (407), 102–118. https://doi.org/10.1097/00003086-200302000-00018
  8. Muschler, G. F., Matsukura, Y., Nitto, H., Boehm, C.A., Valdevit,A.D., Kambic, H. E., Davros, W. J., Easley, K. A. & Powell,K.A. (2005). Selective retention of bone marrow-derived cells to enhance spinal fusion. Clinical orthopaedics and related research, (432), 242–251. https://doi.org/10.1097/01.blo.0000149812.32857.8b
  9. Jaiswal, N., Haynesworth, S. E., Caplan, A. I., & Bruder, S. P. (1997). Osteogenic differentiation of purified, culture expanded human mesenchymal stem cells in vitro. Journal of cellular biochemistry, 64 (2), 295–312.
  10. Muschler, G. F., Boehm, C., & Easley, K. (1997). Aspiration to obtain osteoblast progenitor cells from human bone marrow: the influence of aspiration volume. JBJS, 79 (11), 1699–1709. https://doi.org/10.2106/00004623-199711000-00012
  11. Chatterjea, A., Meijer, G., Van Blitterswijk, C., & De Boer, J. (2010). Clinical application of human mesenchymal stromal cells for bone tissue engineering. Stem Cells Int., 11, 215625. https://doi.org/10.4061/2010/215625 215625.
  12. Dominici, M. L. B. K., Le Blanc, K., Mueller, I., Slaper-Cortenbach, I., Marini, F. C., Krause, D. S., Deans, R. J., Keating, A., Prockop, D. J., & Horwitz, E. M. (2006). Minimal criteria for defining multipotent mesenchymal stromal cells. The International Society for Cellular Therapy position statement. Cytotherapy, 8 (4), 315–317. https://doi.org/10.1080/14653240600855905
  13. Fleming, M. E., Bharmal, H., & Valerio, I. (2014). Regenerative medicine applications in combat casualty care. Regenerative medicine, 9 (2), 179–190. https://doi.org/10.2217/rme.13.96
  14. Cowan, C. M., Shi, Y. Y., Aalami, O. O., Chou, Y. F., Mari, C., Thomas, R., Quarto, N., Contag, C. H., Wu, B., & Longaker, M. T. (2004). Adipose-derived adult stromal cells heal critical-size mouse calvarial defects. Nature biotechnology, 22 (5), 560–567. https://doi.org/10.1038/nbt958
  15. Betz, O., Vrahas, M., Baltzer, A., Lieberman, J. R., Robbins, P. D., & Evans, C.H. (2005). Gene transfer approaches to enhancing bone healing. In: Lieberman, J. R., Friedlaender, G. E. (eds) Bone Regeneration and Repair. Totowa, NJ: Humana Press, 157–168. https://doi.org/10.1385/1-59259-863-3:157
  16. Sallent, I., Capella-Monsonís, H., Procter, P., Bozo, I. Y., Deev, R. V., Zubov, D., Vasyliev, R., Perale, G., Pertici, G., Baker, J. & Zeugolis, D. I. (2020). The few who made it:
  17. commercially and clinically successful innovative bone grafts. Frontiers in bioengineering and biotechnology, 8, 952. https://doi.org/10.3389/fbioe.2020.00952
  18. Vasyliev, R. G., Oksymets, V. M., Rodnichenko, A. E., Zlatska, A. V., Gubar, O. S., Gordiienko, I. M., & Zubov, D. O. (2017). Tissue-engineered bone for treatment of combat related limb injuries. Experimental Oncology, 39 (3), 194–196.
  19. Freshney, R. I. (2015). Culture of animal cells: a manual of basic technique and specialized applications. John Wiley & Sons.
  20. Prockop, D. J., Phinney, D. G., & Bunnell, B. A. (2008). Mesenchymal stem cells: methods and protocols. Totowa, NJ: Humana Press.
  21. Davis, G. E., & Senger, D. R. (2005). Endothelial extracellular matrix: biosynthesis, remodeling, and functions during vascular morphogenesis and neovessel stabilization. Circulation research, 97 (11), 1093–1107. https://doi.org/10.1161/01.RES.0000191547.64391.e3
  22. EMEA/CHMP/410869/2006. EMEA/CHMP Guideline on Human Cell-Based Medicinal Products. Retrieved from https://www.ema.europa.eu/en/documents/scientific-guideline/guideline-human-cell-based-medicinal-products_en.pdf
  23. 21CFR1271. Code of Federal Regulations. Title 21 Food and drugs. Chapt. I – Food and Drug Administration: Department of Health and Human Services. Subchapt. L – Regulations under certain other acts administered by the Food and Drug Administration. Part 1271 – Human cells, tissues, and cellular and tissue-based products: Subpart D – Current Good Tissue Practice. – [up to date as of 11/16/2023, last amended 11/11/2023]. Retrieved from https://www.ecfr.gov/current/title-21/chapter-I/subchapter-L/part1271/subpart-D

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How to Cite

Zubov, D. ., Poliachenko, I. ., Kostrub, O. ., Blonskyi, R. ., Magomedov, O. ., Dolgopolov, O. ., & Zasadnyuk, I. . (2024). Biotechnological aspects of the working-out and manufacturing of living bone equivalent. ORTHOPAEDICS TRAUMATOLOGY and PROSTHETICS, (4), 87–92. https://doi.org/10.15674/0030-59872023487-92

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SHARING OF EXPERIENCE