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Evaluation of osteointegrative and osteoinductive properties of silicon doped ceramics in a model of rabbit’s femur fractures

Bone regeneration is one of the most complex and unique types of tissue regeneration, although quite long in time, comparatively, for example, with soft tissues, but provides the complete identity of the damaged site with normal bone. The most complex fractures are fragmentation, which can be occurs within wide range - 25-60% of the total number of all fractures. In such cases, due to the loss of contact with soft tissues, the fragments lose blood supply and regeneration, which leads to different bone size defect. This condition cause limitation of the main mechanisms of bone consolidation – endoostal and intramembrane ossification. In this regard, a strategic medical treatment is the replacement of bone defect with biological or synthetic material, which creates a site for the processes of reparative osteogenesis.

The most widespread combined biocompatible materials in the various combinations of β-tricalcium phosphate and hydroxyapatite ("Maxresorb®", "Perossal®", "calc-i-oss®CRYSTAL", "easy-graft®CRYSTAL"), or composite composites based on bioactive and biogenic materials: hydroxylapatite + collagen (Biostite, Collagraft, Avitene, Collola, Hapkol, Collapan, MP Composite); hydroxylapatite + tricalcium phosphate + collagen ("Hydroxyapol", "Collapolum"); hydroxylapatite + collagen + sulfated glycosaminoglycans ("Biomatrix", "Osteomatrix", "Bioimplant").

Unfortunately, in veterinary medicine osteotropic materials developed for humane medicine are used only. Recently, a separate group of biocompatible composites based on the combination of hydroxyapatite with β-tricalcium phosphate, doped with magnesium, sodium, potassium, zinc, copper, aluminum, strontium, silicon, germanium, in order to provide them with specific properties - antibacterial, osteoinductive, antitumor, immunomodulating, etc. However, the spectrum of biological effects of these ions on bone metabolism is extremely diverse, and therefore the use of composite ceramics doped with microelement ions requires a comprehensive clinical and experimental justification.

The purpose of the study is to evaluate the osteointegration and osteoinductive properties of ceramics based on hydroxyapatite and β-tricalcium phosphate doped with silicon for model fractures of the femur in rabbits.

The work is done on rabbits of Californian breed at the age of 3 months. and a weight of about 2.5 kg. To substantiate the ceramics GTlKg-2, 2 groups of 10 rabbits were formed in each, in which model bone defects were formed in the distal parts of the hip dysthymia. Animals of the experimental group defects filled with granules of ceramics. In the rabbits of the control group, the defect was left to heal under a blood clot. Animals were extracted from the experiment at the 21st and 42nd day. X-ray and histomorphological studies were performed.

On the 21st day of reparative osteogenesis, rabbits of all groups fully rested on the injured limb, signs of inflammatory reaction were absent in the experimental group, and the control marked the pronounced seal of the periosteum across the entire surface of the femur. It should be noted that hydroxyapatite ceramics does not possess x-ray contrast properties.

On the 42nd day of regeneration of rabbits both groups fully rested on injured limb, signs of inflammatory reaction of soft tissues in the area of injury were absent. Radiologically, in animals of the experimental group in the place of bone defect, spot osteosclerosis was detected in the form of a clearly defined white heel, opposite to which the contour of the periosteum was sealed. At the same time, on the control X-rays, along with a well-defined, but more elongated septum of the periodontal, revealed a bone marrow panossus at the site of the injury, with a clearly defined extension of the eclipse. Substantially complemented macromorphological picture of bone biopsy. In particular, in the case of replacement of bone defect GTlKg-2, at the 21st day in the traumatic areas a limited and moderate periosteal reaction was noted. Along with this, in control animals, in this period, it was not completely replaced by fibrous cartilaginous tissue, as evidenced by its craterial appearance.

Histologically, in the control animals, the bone defect formed a cartilage tissue along the periphery, and the bone beams, which were at a certain distance from the place of the defect, were at the stage of resorption. In the case of its replacement granules GTlKg-2 formed bone-ceramic regenerate, that is, the intervals between the granules are filled with bone tissue. The obtained results give grounds to consider that GTlKg-2 contributes to the formation of bone tissue due to its osteointegration and osteoinductive properties.

Key words: reparative osteogenesis, osteointegration, osteocytes, osteoblasts, hydroxyapatite composite with β-tricalcium phosphate, doped with silicon.

1. Rublenko, S.V., Єroshenko, O.V., (2012). Monіtoring veterinarnoї dopomogi і struktura hіrurgіchnoї patologії sered drіbnih domashnіh tvarin v umovah mіs'koї klіnіki [Monitoring of veterinary care and the structure of surgical pathology among small domestic animals in the conditions of a city clinic]. Vіsnik Sums'kogo NA [Visnyk of Sumy NAU].  Sumy,  Issue 1 (30), pp. 150-154.

2. Semenjak, S.A., Rublenko, S.V., Danilejko, Ju.M. (2014). Struktura perelomіv kіstok u sobak v umovah megapolіsu [Structure of fractures of bones in dogs in conditions of megacity]. Vіsnik Bіlocerkіv. nac. agrar. un-tu.[ Bulletin Herald. nats agrar un-th] Bila Tserkva city, Issue 13 (108),  pp. 218-223.

3. Pustovіt, R.V., Danilejko, Ju.M., Rublenko, M.V. (2006). Monіtoring hіrurgіchnoї patologії sered drіbnih domashnіh tvarin DLVM u Kiїvs'komu rajonі m. Odesi za 2003–2005 roki [Monitoring of surgical pathology among small domestic animals of the DLWM in the Kyiv region of Odessa in 2003-2005]. Vіsnik Bіlocerkіv. derzh. agrar. un–tu. [Bulletin Herald. state agrar un-th]. Bila Tserkva city, Issue 36, pp. 132–137.

4. Teljatnіkov, A.V., (2013). Poshirennja perelomіv kіstok u sobak [Distribution of bone fractures in dogs]. Naukovij vіsnik veterinarnoї medicini: Zb. nauk. prac'.[ Scientific Herald of Veterinary Medicine: Sb. sciences works]. Bila Tserkva city,  Issue 11 (101), pp. 149–153.

5. Pustovіt, R.V., (2007). Harakteristika perelomіv trubchastih kіstok u drіbnih domashnіh tvarin [Characteristics of fractures of tubular bones in small pet animals]. Vіsnik Bіlocerkіv. derzh. agrar. un–tu. [Bulletin Herald. state agrar un-th].  Bila Tserkva city,  Issue 44, pp. 124–127.

6. Haaland, P.J., Sjöström, L., Devor, M.  Appendicular fracture repair in dogs using the locking compression plate system: 47 cases. Vet. Comp. Orthop Traumatol. 2009,  Vol. 4, pp. 309–315.

7. Nandi, S.K., Ghosh, S.K., Kundu, B., De, D.K. Evaluation of new porous β-tri-calcium phos¬phate ceramic as bone substitute in goat model.  Small Ruminant Res.  2008,  Vol. 75, pp. 144–153.

8. Oryan, A., Alidadi, S., Bigham-Sadegh, A., Meiman¬di-Parizi, A. Chitosan/gelatin/platelet gel enriched by a combination of hydroxyapatite and beta-tri¬calcium phosphate in healing of a radial bone de-fect model in rat.  Int J Biol Macromol.  2017, Vol. 101, pp. 630–637.

9. Podaropoulos, L., Veis, A.A., Papadimitriou, S., Alex andridis C, Oral. Bone regeneration using b-tricalcium phosphate in a calcium sulfate matrix.  Implantol.  2009,  Vol. 35, pp. 28–36.

10. Oryan, A., Alidadi, S., Moshiri, A., Maffulli, N. Bone regenerative medicine: classic options, novel strategies, and future directions. J. Orthop Surg Res. 2014,  Vol. 9. (1), pp. 29–36.

11. Keating, J. Substitutes for autologous bone graft in orthopaedic trauma. J Bone Joint Surg Br. 2001, Vol. 83-B,  pp. 3–8.

12. Fukui, N., Sato, T., Kuboki, Y., Aoki, H. Bone tissue reaction of nanohydroxyapatite collagen composite at the early stage of implantation.  Biomed Eng Mater.  2008, Vol. 18 (1), pp.  25–33.

13. Chim, H. Biomaterials in craniofacial surgery: experimental studies and clinical application. Craniofac. Surg.  2009, Vol. 20 (1),  pp.  29–33.

14. Cheng, L.J., Yu, T., Shi, Z. Osteoinduction Mechanism of Calcium Phosphate Biomaterials In Vivo: A Review. JOURNAL OF BIOMATERIALS AND TISSUE ENGINEERING.  2017,  Vol. 7,  pp. 911–918.

15. Angelescu, A., Kleps, I., Mihaela, M. Rev. Porous silicon matrix for applications in biology.  Adv. Sci.  2003,  Vol. 5, pp. 440–449.

16. Maximillian, C.O., Andi, A.I., Mochammad, H. Effects of platelet-rich plasma and carbonated hydroxyapatite combination on cranial defect Bone Regeneration: An animal study. Wound Medicine.  2018,  Vol. 21,  pp. 12–15.

17. Ghosh, S.K., Nandi, S.K., Kundu, B. In vivo response of porous hydroxyapatite and β‐tricalcium phosphate prepared by aqueous solution combustion method and comparison with bioglass scaffolds. J. Biomed Mater Res B. Appl Bio-mater.  2008,  Vol. 86,  pp. 217–227.

18. Lee, D.S., Pai, Y., Chang, S., Kim, D. Microstructure, physical properties, and bone regeneration efect of the nano sized β-tricalcium phosphate granules.  Mater. Sci. Eng.  2016,  Vol. 58,  pp. 971–976.

19. Dorozhkin, S. V. Calcium orthophosphate-containing biocomposites and hybrid biomaterials for biomedical applications. Journal of Functional Biomaterials. 2015,  Vol. 6, pp. 708–832.

20. Huang, Y., Wu, C., Zhang, X., Chang,  J.  Regulation of immune response by bioactive ions released from silicate bioceramics for bone regeneration. Acta Biomaterialia.  2017,  Vol. 3, pp. 48–57.

21. Uvarova, І.V., Gorbik, P.P., Gorobec', S.V. (2014). Nanomaterіali medichnogo priznachennja [Nanomaterials for medical purposes]. Kyiv, Nauk. Dumka,    416 p.

22. Rublenko, M.V., Andrіjec', V.G., Semenjak, S.A., Ul'janchich, N.V.  (2015). Vikoristannja kompozitnih materіalіv za perelomіv trubchastih kіstok u tvarin [Use of composite materials for fractures of tubular bones in animals].   Bila Tserkva city,   86 p.

23. O’Neill, E., Awale, G.,  Daneshm, L., Umerah, O. The roles of ions on bone regeneration.  Drug discovery today.  2018, Vol. 23 (4),  pp. 879–890.

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