CHANGES IN MARKERS OF BONE TISSUE REMODELING AND THE INFLAMMATORY PROCESS IN THE BLOOD SERUM OF WHITE RATS IN CASE OF DEFECT FILLING OF THE FEMUR WITH IMPLANTS BASED ON POLYLACTIDE AND TRICALCIUMPHOSPHATE WITH MESENCHYMAL STEM CELLS

Authors

  • Nazar Gontar Educational and Scientific Institute of Postgraduate Education of Kharkiv National Medical University. Ukraine, Ukraine

DOI:

https://doi.org/10.15674/0030-59872023233-42

Keywords:

Defect, modeling, regeneration, xenoimplant, polylactide, tricalcium phosphate, mesenchymal stem cell, biochemistry, connective tissue

Abstract

Objective. Based on the analysis of markers of inflammation and metabolism of bone tissue in the blood serum of laboratory rats, to evaluate the course of bone remodeling after filling the defect in the distal metaphysis of the femur with 3D-printed implants based on polylactide and tricalcium phosphate (3D-I) alone or in combination with mesenchymal stromal cells (MSCs). Methods. 53 white rats were used, which were divided into groups: intact (5 animals) — the operation was not performed; Control (15) — 3D-I; Experiment I (15) — 3D-I + cultured alloMSCs; Experiment II (15) — 3D-I + introduction of alloMSCs into the area of surgical intervention 7 days after implantation. The following were studied: the content of glycoproteins (GP), interleukin-6 (IL-6), osteocalcin, chondroitin sulfates (CS), total protein, calcium, alkaline (AlP) and acid phosphatase (AP) activity, and their ratio, mineralization indices were calculated. Results. Compared with intact animals, higher indicators were determined in the rats of the Control group: the content of GP by 39.73; 32.88; 23.29 %; CS — 250.00; 222.09 and 196.51 %, AlP activity — 81.67, 51.03, 39.36 %, on the 15th, 30th, and 90th days of the experiment; IL-6 — 44.89; 60.06 % on the 15th and 30th days. In the rats of the Experiment I g roup: the content of GP — by 82.19; 65.75, 57.53 %, IL-6 — 72.14; 96.59; 79.88 %, CS — 306.98; 276.74; 253.49 %; AlP activity — 63.73; 129.70; 51.28 %, on the 15th, 30th and 90th days of the experiment. In the Experiment II group: on the 15th, 30th and 90th days, the content of GP was higher by 27.40; 26.03; 129.18 %; CS — by 175.58; 137.21 and 115.12 %; AlP activity — 192.99; 178.02, 76.31 %; on the 15th and 30th days: IL-6 — by 37.46; 20.74 %. Conclusions. In the case of filling the defect with 3D-printed implants, biochemical signs of moderate inflammation were determined; 3D-printed implants together with MSCs — pronounced inflammation, slowing of bone formation, formation of connective tissue; 3D-printed implants with postoperative injection of MSCs — moderate inflammation and optimal conditions for healing the defect with bone tissue.

Author Biography

Nazar Gontar, Educational and Scientific Institute of Postgraduate Education of Kharkiv National Medical University. Ukraine

MD

References

  1. Lin, H., Sohn, J., Shen, H., Langhans, M. T., & Tuan, R. S. (2019). Bone marrow mesenchymal stem cells: Aging and tissue engineering applications to enhance bone healing. Biomaterials, 203, 96–110. https://doi.org/10.1016/j.biomaterials.2018.06.026
  2. Pollock, F. H., Maurer, J. P., Sop, A., Callegai, J., Broce, M., Kali, M., & Spindel, J. F. (2020). Humeral Shaft Fracture Healing Rates in Older Patients. Orthopedics, 43(3), 168–172. https://doi.org/10.3928/01477447-20200213-03
  3. Dedhia, N., Ranson, R. A., Rettig, S. A., Konda, S. R., & Egol, K. A. (2023). Nonunion of conservatively treated humeral shaft fractures is not associated with anatomic location and fracture pattern. Archives of orthopaedic and trauma surgery, 143(4), 1849–1853. https://doi.org/10.1007/s00402-022-04388-3
  4. Korzh, M, Vorontsov, P., Ashukina, N, & Maltseva, V. (2021). Age-related features of bone regeneration (literature review). Orthopaedics, Traumatology and Prosthetics, (3), 92–100. https://doi.org/10.15674/0030-59872021392-100
  5. Ambrosi, T. H., Marecic, O., McArdle, A., Sinha, R., Gulati, G. S., Tong, X., Wang, Y., Steininger, H. M., Hoover, M. Y., Koepke, L. S., Murphy, M. P., Sokol, J., Seo, E. Y.,
  6. Tevlin, R., Lopez, M., Brewer, R. E., Mascharak, S., Lu, L., Ajanaku, O., Conley, S. D., … Chan, C. K. F. (2021). Aged skeletal stem cells generate an inflammatory degenerative niche. Nature, 597(7875), 256–262. https://doi.org/10.1038/s41586-021-03795-7
  7. Baldwin, P., Li, D. J., Auston, D. A., Mir, H. S., Yoon, R. S., & Koval, K. J. (2019). Autograft, Allograft, and Bone Graft Substitutes: Clinical Evidence and Indications for Use in the Setting of Orthopaedic Trauma Surgery. Journal of orthopaedic trauma, 33(4), 203–213. https://doi.org/10.1097/BOT.0000000000001420
  8. Brunello, G., Panda, S., Schiavon, L., Sivolella, S., Biasetto, L., & Del Fabbro, M. (2020). The Impact of Bioceramic Scaffolds on Bone Regeneration in Preclinical In Vivo Studies: A Systematic Review. Materials (Basel, Switzerland), 13(7), 1500. https://doi.org/10.3390/ma13071500
  9. Yishan Chen, Junxin Lin, Yeke Yu, & Xiaotian Du (2020). Role of mesenchymal stem cells in bone fracture repair and regeneration. In Ahmed H. K. El-Hashash (Eds.), Mesenchymal Stem Cells in Human Health and Diseases (pp.127‒143). Academic Press. https://doi.org/10.1016/B978-0-12-819713-4.00007-4
  10. On protection of animals from cruel treatment: Law of Ukraine №3447-IV of February 21, 2006. The Verkhovna Rada of Ukraine. (In Ukrainian). URL: http://zakon.rada.gov.ua/cgi-bin/laws/main.cgi?nreg=3447-15
  11. European Convention for the protection of vertebrate animals used for research and other scientific purposes. Strasbourg, 18 March 1986: official translation. Verkhovna Rada of Ukraine. (In Ukrainian). URL: http://zakon.rada.gov.ua/cgi-bin/laws/main.cgi?nreg=994_137. 21
  12. DIRECTIVE 2010/63/EU OF THE EUROPEAN PARLIAMENT AND OF THE COUNCIL of 22 September 2010 on the protection of animals used for scientific purposes (Text with EEA relevance). Official Journal of the European Union, 2010, 276/33 – 276/79. https://eur-lex.europa.eu/LexUriServ/
  13. LexUriServ.do?uri=OJ:L:2010:276:0033:0079:en:PDF
  14. Ashukinа, N. O., Vorontsov, P. M., Maltseva, V. Ye., Danуshchuk, Z. M., Nikolchenko, O. A., Samoylova, K. M., & Husak V. S. (2022). Morphology of the repair of critical size bone defects which filling allogeneic bone implants in combination with mesenchymal stem cells depending on the recipient age in the experiment. Orthopaedics, Traumatology and Prosthetics, (3‒4), 80‒90. http://dx.doi.org/10.15674/0030-598720223-480-90
  15. Poser, L., Matthys, R., Schawalder, P., Pearce, S., Alini, M., & Zeiter, S. (2014). A standardized critical size defect model in normal and osteoporotic rats to evaluate bone tissue engineered constructs. BioMed research international, 2014, 348635. https://doi.org/10.1155/2014/348635
  16. Tao, Z. S., Wu, X. J., Zhou, W. S., Wu, X. J., Liao, W., Yang, M., Xu, H. G., & Yang, L. (2019). Local administration of aspirin with β-tricalcium phosphate/poly-lactic-co-glycolic acid(β-TCP/PLGA) could enhance osteoporotic bone regeneration. Journal of bone and mineral metabolism, 37(6), 1026–1035. https://doi.org/10.1007/s00774-019-01008-w
  17. Kamyshnikov, V. S. (2003). Clinical and biochemical laboratory diagnostics: reference book: in 2 volumes [Kliniko-biokhimicheskaya laboratornaya diagnostika: spravochnik: v 2 t.] (2nd ed.). Minsk : Interpressservice. (in russian).
  18. Morozenko, D. V., Leontieva, F. S. (2016). Research methods markers of connective tissue metabolism in modern clinical and experimental medicine [Metody doslidzhennya markeriv metabolizmu spoluchnoyi tkanyny u klinichniy ta eksperymental ʹniy medytsyni]. Molodyy vchenyy, 2 (29), 168–172. (in Ukrainian)
  19. Lang, T. A., Sesik, M. M. (2011). How to describe statistics in medicine. A guide for authors, editors and reviewers [Kakopisyvat' statistiku v meditsine. Rukovodstvo dlya avtorov, redaktorov i retsenzentov]. Moscow : Practical Medicine. (in russian)
  20. Rolvien, T., Barbeck, M., Wenisch, S., Amling, M., & Krause, M. (2018). Cellular Mechanisms Responsible for Success and https://eur-lex.europa.eu/LexUriServ/
  21. LexUriServ.do?uri=OJ:L:2010:276:0033:0079:en:PDF Failure of Bone Substitute Materials. International journal of molecular sciences, 19(10), 2893. https://doi.org/10.3390/ijms19102893
  22. Lee, T. D., Zhang, H., Wang, H., & Chang, L.-F. (2018). Cellular factors derived from mesenchymal stem and progenitor cells with regeneration effects. Asia-Pacific Journal of Blood Types and Genes. https://doi.org/10.46701/apjbg.2018012017062
  23. Wang, X., Jiang, H., Guo, L., Wang, S., Cheng, W., Wan, L., Zhang, Z., Xing, L., Zhou, Q., Yang, X., Han, H., Chen, X., & Wu, X. (2021). SDF-1 secreted by mesenchymal stem cells promotes the migration of endothelial progenitor cells via CXCR4/PI3K/AKT pathway. Journal of molecular histology, 52(6), 1155–1164. https://doi.org/10.1007/s10735-021-10008-y

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How to Cite

Gontar, N. . (2023). CHANGES IN MARKERS OF BONE TISSUE REMODELING AND THE INFLAMMATORY PROCESS IN THE BLOOD SERUM OF WHITE RATS IN CASE OF DEFECT FILLING OF THE FEMUR WITH IMPLANTS BASED ON POLYLACTIDE AND TRICALCIUMPHOSPHATE WITH MESENCHYMAL STEM CELLS. ORTHOPAEDICS TRAUMATOLOGY and PROSTHETICS, (2), 33–42. https://doi.org/10.15674/0030-59872023233-42

Issue

No. 2 (2023)

Section

ORIGINAL ARTICLES

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