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Enhanced Osteogenesis of Nanosized Cobalt-substituted Hydroxyapatite

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Abstract

Hydroxyapatite (HAp) is an extensively studied material with known biocompatible and osteoconductive properties in bone tissue reconstruction. The improvement of the osteogenetic potential of HAp has been tested through modification of its structure, by replacing Ca2+ ions with Co2+ ions. In our study, we comparatively analyze the osteogenetic potential of the synthesized HAp and Co2+-substituted HAp (HAp/Co) designed on the nano-scale with the aim of specifically stimulating osteogenesis in vivo. We present a quantitative study of the microscopic organization and structure of the newly formed tissue in a bone defect after 12 weeks and 24 weeks. A quantitative analysis of the calcium, magnesium and phosphorus content in the defect and its close environment was used to determine the deposition of minerals after bone reconstruction. The defect reconstructed with HAp/Co nanoparticles (Co2+ content 12 wt%) was filled with a new tissue matrix composed of dense collagen fibers containing centers of mineralization after 24 weeks. The mineral deposition rate was also higher when the defect was reconstructed with HAp/Co than when it was filled with pure HAp. A histological analysis confirmed that the alveolar bone, in which osteoporosis-induced defects were repaired using HAp/Co nanoparticles, was recuperated.

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References

  1. Eriksen E, Keaveny T, Gallagher E, Krege J. Literature review: The effects of teriparatide therapy at the hip in patients with osteoporosis. Bone, 2014, 67, 246–256.

    Article  Google Scholar 

  2. Samavedi S, Whittington A, Goldstein A. Calcium phosphate ceramics in bone tissue engineering: A review of properties and their influence on cell behavior. Acta Bio-materialia, 2013, 9, 8037–8045.

    Article  Google Scholar 

  3. Parsons A J, Ahmed I, Han N, Felfel R, Rudd C D. Mimicking bone structure and function with structural composite materials. Journal of Bionic Engineering, 2010, 7, S1–S10.

    Article  Google Scholar 

  4. Dorozhkin S. Calcium orthophosphates in nature, biology and medicine. Materials, 2009, 2, 399–498.

    Article  Google Scholar 

  5. Lin K, Wu C, Chang J. Advances in synthesis of calcium phosphate crystals with controlled size and shape. Acta Biomaterialia, 2014, 10, 4071–4102.

    Article  Google Scholar 

  6. Uskoković V, Uskoković D. Nanosized hydroxyapatite and other calcium phosphates: Chemistry of formation and application as drug and gene delivery agents. Journal of Biomedical Materials Research Part B: Applied Biomaterials, 2011, 96, 152–191.

    Article  Google Scholar 

  7. Dorozhkin S. Nanosized and nanocrystalline calcium orthophosphates. Acta Biomaterialia, 2010, 6, 715–734.

    Article  Google Scholar 

  8. Thian E, Konishi T, Kawanobe Y, Lim P, Choong C, Ho B, Aizawa M. Zinc-substituted hydroxyapatite: A biomaterial with enhanced bioactivity and antibacterial properties. Journal of Materials Science: Materials in Medicine, 2013, 24, 437–445.

    Google Scholar 

  9. Cox S, Jamshidi P, Grover L, Mallick K. Preparation and characterisation of nanophase Sr, Mg, and Zn substituted hydroxyapatite by aqueous precipitation. Materials Science and Engineering: C, 2014, 35, 106–114.

    Article  Google Scholar 

  10. Stojanović Z, Veselinović Lj, Marković S, Ignjatović N. Uskoković D. Hydrothermal synthesis of nanosize pure and cobalt-exchanged hydroxyapatite. Materials and Manufacturing Processes, 2009, 24, 1096–1103.

    Article  Google Scholar 

  11. Kramer E, Itzkowitz E, Wei M. Synthesis and characterization of cobalt-substituted hydroxyapatite powders. Ceramics International, 2014, 40, 13471–13480.

    Article  Google Scholar 

  12. Tank K, Chudasama K, Thaker V, Joshi M. Cobalt-doped nanohydroxyapatite: Synthesis, characterization, antimicrobial and hemolytic studies. Journal of Nanoparticle Research, 2013, 15, 1644–1655.

    Article  Google Scholar 

  13. Darolles C, Sage N, Armengaud J, Malard V. In vitro assessment of cobalt oxide particle toxicity: Identifying and circumventing interference. Toxicology in Vitro, 2013, 27, 1699–1710.

    Article  Google Scholar 

  14. Smith L, Holmes A, Kumar Kandpal S, Mason M, Zheng T, Wise J Sr. The cytotoxicity and genotoxicity of soluble and particulate cobalt in human lung fibroblast cells. Toxicology and Applied Pharmacology, 2014, 278, 259–265.

    Article  Google Scholar 

  15. Fan W, Crawford R, Xiao Y. Enhancing in vivo vascularized bone formation by cobalt chloride-treated bone marrow stromal cells in a tissue engineered periosteum model. Biomaterials, 2010, 31, 3580–3589.

    Article  Google Scholar 

  16. Bose S, Fielding G, Tarafder S, Bandyopadhyay A. Understanding of dopant-induced osteogenesis and angiogenesis in calcium phosphate ceramics. Trends in Biotechnology, 2013, 31, 594–605.

    Article  Google Scholar 

  17. Wu C, Zhou Y, Fan W, Han P, Chang J, Yuen J, Zhang M, Xiao Y. Hypoxia-mimicking mesoporous bioactive glass scaffolds with controllable cobalt ion release for bone tissue engineering. Biomaterials, 2012, 33, 2076–2085.

    Article  Google Scholar 

  18. Veselinović Lj, Karanović Lj, Stojanović Z, Bracko I, Marković S, Ignjatović N, Uskoković D. Crystal structure of cobalt-substituted calcium hydroxyapatite nanopowders prepared by hydrothermal processing. Journal of Applied Crystallography, 2010, 43, 320–327.

    Article  Google Scholar 

  19. Ignjatović N, Ajduković Z, Savić V, Najman S, Mihailović D, Vasiljević P, Stojanović Z, Uskoković V, Uskoković D. Nanoparticles of cobalt-substituted hydroxyapatite in regeneration of mandibular osteoporotic bones. Journal of Materials Science: Materials in Medicine, 2013, 24, 343–354.

    Google Scholar 

  20. Ajduković Z, Najman S, Djordjević Lj, Savić V, Petrović D, Ignjatović N, Uskoković D. Repair of bone tissue affected by osteoporosis with hydroxyapatite-poly-L-(HAp/PLLA) with and without blood plasma. Journal of Biomaterials Application, 2005, 20, 179–190.

    Article  Google Scholar 

  21. Dempster D, Compston J, Drezner M, Glorieux F, Kanis J, Malluche H, Meunier P, Ott S, Recker R, Parfitt M. Standardized nomenclature, symbols, and units for bone histo-morphometry: A 2012 update of the report of the ASBMR histomorphometry nomenclature committee. Journal of Bone and Mineral Research, 2013, 28, 2–17.

    Article  Google Scholar 

  22. Drašler B, Drobne D, Novak S, Valant J, Boljte S, Otrin L, Rappolt M, Sartori B, Iglič A, Kralj-Iglič V, Šuštar V. Makovec D, Gyergyek S, Hočevar M, Godec M, Zupanc J. Effects of magnetic cobalt ferrite nanoparticles on biological and artificial lipid membranes. International Journal of Nanomedicine, 2014, 9, 1559–1581.

    Article  Google Scholar 

  23. Simonsen L, Harbak H, Bennekou P. Cobalt metabolism and toxicology–a brief update. Science of the Total Environment, 2012, 432, 210–215.

    Article  Google Scholar 

  24. Maier J, Bernardini D, Rayssiguier Y, Mazur A. High concentrations of magnesium modulate vascular endothelial cell behaviour in vitro. Biochimica et Biophysica Acta (BBA) -Molecular Basis of Disease, 2004, 1689, 6–12.

    Article  Google Scholar 

  25. Cooke J, Losordo D. Nitric oxide and angiogenesis. Circulation, 2002, 105, 2133–2135.

    Article  Google Scholar 

  26. Ripamonti U. Biomimetism, biomimetic matrices and the induction of bone formation. Journal of Cellular and Molecular Medicine, 2009, 13, 2953–2972.

    Article  Google Scholar 

  27. Nudelman F, Pieterse K, George A, Bomans P, Friedrich H, Brylka L, Hilbers P, de With G, Sommerdijk N. The role of collagen in bone apatite formation in the presence of hydroxyapatite nucleation inhibitors. Nature Materials, 2010, 9, 1004–1009.

    Article  Google Scholar 

  28. Mata A, Geng Y, Henrikson J, Aparicio C, Stock R, Satcher R, Stupp I. Bone regeneration mediated by biomimetic mineralization of a nanofiber matrix. Biomaterials, 2010, 31, 6004–6012.

    Article  Google Scholar 

  29. Kikuchi M, Ikoma T, Itoh S, Matsumoto N, Koyama Y, Takakuda K, Shinomiya K, Tanaka J. Biomimetic synthesis of bone-like nanocomposites using the self-organization mechanism of hydroxyapatite and collagen. Composites Science and Technology, 2004, 64, 819–825.

    Article  Google Scholar 

  30. Ryadnov M, Woolfson D. Engineering the morphology of a self-assembling protein fibre. Nature Materials, 2003, 2, 329–332.

    Article  Google Scholar 

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Correspondence to Dragan Uskoković.

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Ignjatović, N., Ajduković, Z., Rajković, J. et al. Enhanced Osteogenesis of Nanosized Cobalt-substituted Hydroxyapatite. J Bionic Eng 12, 604–612 (2015). https://doi.org/10.1016/S1672-6529(14)60150-5

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