Comparative Study of the Effects of Strontium and Magnesium Ions on Physical and Chemical Properties of Calcium Phosphate-Gelatin Biomimetic Scaffolds in Bone Tissue Engineering
Subject Areas :Amirhossein Moghanian 1 , Majid Raz 2 , Fathollah Moztarzadeh 3
1 - Department of Materials Engineering, Imam Khomeini International University, Qazvin, 34149-16818, Iran
2 - Department of Engineering, Shahryar branch, Islamic azad university, Shahryar, Iran
3 - Biomaterial Group, Faculty of Biomedical Engineering (Center of Excellence), Amirkabir University of Technology, Tehran, Iran
Keywords: Bone, Magnesium, scaffold, strontium, Biomimetic, G292 Osteoblast cell,
Abstract :
In this study, biomimetic scaffolds were designed to study the formation of calcium phosphate deposits by using a double diffusion method into gelatin hydrogel in temperature and pH similar to body conditions. Moreover, the effect of magnesium (Mg) and strontium (Sr) ions on properties was investigated. Five different types of specimens with different Sr and Mg ions percentage were synthesized and then porous scaffolds were prepared by freeze-drying method. The scaffolds microstructures were examined by scanning electron microscopy (SEM), which showed a smooth and needle-shaped surface of specimens. Fourier transform infrared spectroscopy (FTIR) results indicated the presence of phosphate and hydroxyl bonds in the structure of the scaffolds, due to the formation of calcium phosphate phases such as HA. The presence of metal ions in the structure caused the displacement of the peaks in X-ray diffraction (XRD) analysis and lattice parameters. Additionally, osteoblast cell culture results also demonstrated M10 and S10 specimens had proper biocompatibility. Additionally, alkaline phosphate (ALP) activity revealed the optimal amount of 10 mol. % Mg and Sr (M10 and S10), which led to the significantly (**p< 0.01, ***p <0.001) growth, proliferation, and differentiation of 292G osteoblasts cells in scaffolds. Moreover, the presence of calcium phosphate improved the biological properties of the specimens. Finally, the results of various analyses confirmed the high capability of the synthesized scaffold as a promising substitute for bone tissue.
[1] G. Schett, "4 - Biology, Physiology, and Morphology of Bone A2 - Firestein, Gary S. In: Budd RC, Gabriel SE, McInnes IB, O'Dell JR, editors", Kelley's Textbook of Rheumatology (Ninth Edition), Philadelphia: W.B. Saunders, pp. 61-6, 2013.
[2] B. D. Boyan, D. J. Cohen & Z. Schwartz, "7.17 Bone Tissue Grafting and Tissue Engineering Concepts☆ A2 – Ducheyne", Paul. Comprehensive Biomaterials II, Oxford: Elsevier, pp. 298-313, 2017.
[3] F. Jakob, R. Ebert, A. Ignatius, T. Matsushita, Y. Watanabe, J. Groll & et al, "Bone tissue engineering in osteoporosis", Maturitas, vol. 75, pp. 118-24, 2013.
[4] S. Naahidi, M. Jafari, M. Logan, Y. Wang, Y. Yuan, H. Bae & et al, "Biocompatibility of hydrogel-based scaffolds for tissue engineering applications", Biotechnology Advances, vol. 35, pp. 530-44, 2017.
[5] S. Deepthi, J. Venkatesan, S. K. Kim, J. D. Bumgardner & R. Jayakumar. "An overview of chitin or chitosan/nano ceramic composite scaffolds for bone tissue engineering", International Journal of Biological Macromolecules, vol. 93, pp. 1338-53, 2016.
[6] م. نصر اصفهانی، "تأثیر تابش نور فرابنفش بر زیست فعالی پوششهای هیبریدی نانو ساختار پلی سیلوکسان-تیتانیوم دیاکسید- شیشه زیستی بهروش سل- ژل"، فصلنامه علمی- پژوهشی فرآیندهای نوین در مهندسی مواد، سال 9، شماره 4، صفحه 129-137، 1394.
[7] F. J. O'Brien, "Biomaterials & scaffolds for tissue engineering", Materials Today, vol. 14, pp. 88-95, 2011.
[8] S. Kuttappan, D. Mathew & M. B. Nair. "Biomimetic composite scaffolds containing bio ceramics and collagen/gelatin for bone tissue engineering - A mini review", International Journal of Biological Macromolecules, vol. 93, pp.1390-401, 2016.
[9] C. Liu, "10 - Collagen–hydroxyapatite composite scaffolds for tissue engineering A2 – Mucalo", Michael. Hydroxyapatite (Hap) for Biomedical Applications: Woodhead Publishing, pp. 211-34, 2015.
[10] K. R. Razali, N. F. M. Nasir, E. M. Cheng, N. Mamat, M. Mazalan, Y. Wahab & et al, "The effect of gelatin and hydroxyapatite ratios on the scaffolds' porosity and mechanical properties", 2014 IEEE Conference on Biomedical Engineering and Sciences (IECBES), pp. 256-9, 2014.
[11] م. خورسند قاینی، "بررسی خصوصیات حرارتی کامپوزیت پلی لاکتیک اسید با ذرات شیشه زیست فعال 45S5 و هیدروکسی آپاتیت (HA) به منظور استفاده در پیچ های تداخلی قابل جذب"، فصلنامه علمی- پژوهشی فرآیندهای نوین در مهندسی مواد، سال 11، شماره 4، صفحه 55-56، 1396.
[12] M. Schumacher, A. Henss, M. Rohnke & M. Gelinsky, "A novel and easy-to-prepare strontium (II) modified calcium phosphate bone cement with enhanced mechanical properties", Acta Biomater, vol. 9, pp. 7536-44, 2013.
[13] E. Bonnelye, A. Chabadel, F. Saltel & P. Jurdic, "Dual effect of strontium ranelate: Stimulation of osteoblast differentiation and inhibition of osteoclast formation and resorption in vitro", Bone, vol. 42, pp. 129-38, 2008.
[14] A. Bigi, E. Boanini, C. Capuccini & M. Gazzano, "Strontium-substituted hydroxyapatite nanocrystals", Inorganica Chimica Acta, vol. 360, pp. 1009-16, 2007.
[15] K. Zhu, K. Yanagisawa, R. Shimanouchi, A. Onda & K. Kajiyoshi, "Preferential occupancy of metal ions in the hydroxyapatite solid solutions synthesized by hydrothermal method", Journal of the European Ceramic Society, vol. 26, pp. 509-13, 2006.
[16] RM. S. Echeverría & M. L. Montero, "Electrolytic one-pot synthesis of Group II nanohydroxyapatites", Journal of Materials Science, vol. 48, pp. 5253-60, 2013.
[17] V. Aina, L. Bergandi, G. Lusvardi, G. Malavasi, F. E. Imrie, I. R. Gibson & et al, "Sr-containing hydroxyapatite: morphologies of HA crystals and bioactivity on osteoblast cells", Materials Science and Engineering: C, vol. 33, pp. 1132-42, 2013.
[18] M. Šupová, "Substituted hydroxyapatites for biomedical applications: A review", Ceramics International, vol. 41, pp. 9203-31, 2015.
[19] S. Lala, M. Ghosh, P. K. Das, D. Das, T. Kar & S. K. Pradhan, "Magnesium substitution in carbonated hydroxyapatite: Structural and microstructural characterization by Rietveld's refinement", Materials Chemistry and Physics, vol. 170, pp. 319-29, 2016.
[20] A. Farzadi, F. Bakhshi, M. Solati-Hashjin, M. Asadi-Eydivand & N. A. A. Osman, "Magnesium incorporated hydroxyapatite: Synthesis and structural properties characterization", Ceramics International, vol. 40, pp. 6021-9, 2014.
[21] L. Bertinetti, C. Drouet, C. Combes, C. Rey, A. Tampieri, S. Coluccia & et al, "Surface Characteristics of Nanocrystalline Apatites: Effect of Mg Surface Enrichment on Morphology, Surface Hydration Species, and Cationic Environments", Langmuir, vol. 25, pp. 5647-54, 2009.
[22] M. Julien, I. Khairoun, R. Z. LeGeros, S. Delplace, P. Pilet, P. Weiss & et al, "Physico-chemical–mechanical and in vitro biological properties of calcium phosphate cements with doped amorphous calcium phosphates", Biomaterials, vol. 28, pp. 956-65, 2007.
[23] Z. S. Tao, W. S. Zhou, X. W. He, W. Liu, B. L. Bai, Q. Zhou & et al, "A comparative study of zinc, magnesium, strontium-incorporated hydroxyapatite-coated titanium implants for osseointegration of osteopenic rats", Materials Science and Engineering. C, vol. 62, pp. 226-32, 2016.
[24] T. Kokubo & H. Takadama, "How useful is SBF in predicting in vivo bone bioactivity?", Biomaterials, vol. 27, pp. 2907-15, 2006.
[25] R. I. Freshney, "Culture of Tumor Cells. Culture of Animal Cells: John Wiley & Sons", Inc, pp. 463-79, 2010.
[26] R. I. Freshney, "Cytotoxicity. Culture of Animal Cells: John Wiley & Sons", Inc., pp. 365-81, 2010.
[27] L. Stipniece, K. Salma-Ancane, N. Borodajenko, M. Sokolova, D. Jakovlevs & L. Berzina-Cimdina, "Characterization of Mg-substituted hydroxyapatite synthesized by wet chemical method", Ceramics International, vol. 40, pp. 3261-7, 2014.
[28] D. Laurencin, N. Almora-Barrios, N. H. De Leeuw, C. Gervais, C. Bonhomme, F. Mauri & et al, "Magnesium incorporation into hydroxyapatite", Biomaterials, vol. 32, pp. 1826-37, 2011.
[29] J. Kolmas, A. Jaklewicz, A. Zima, M. Bućko, Z. Paszkiewicz, J. Lis & et al, "Incorporation of carbonate and magnesium ions into synthetic hydroxyapatite: The effect on physicochemical properties", Journal of Molecular Structure, vol. 987, pp. 40-50, 2011.
[30] M. Frasnelli, F. Cristofaro, V. M. Sglavo, S. Dire, E. Callone, R. Ceccato & et al, "Synthesis and characterization of Strontium-substituted hydroxyapatite nanoparticles for bone regeneration", Materials Science and Engineering: C, vol.71, pp.653-62, 2017.
[31] S. S. Singh, A. Roy, B. Lee, I. Banerjee & P. N. Kumta, "Synthesis, characterization, and invitro cytocompatibility of amorphous β-tri-calcium magnesium phosphate ceramics", Materials Science and Engineering: C, vol. 67, pp. 636-45, 2016.
[32] B. Thavornyutikarn, N. Chantarapanich, K. Sitthiseripratip, G. A. Thouas & Q. Chen, "Bone tissue engineering scaffolding: computer-aided scaffolding techniques", Progress in Biomaterials, vol. 3, pp. 61-102, 2014.
[33] L. Roseti, V. Parisi, M. Petretta, C. Cavallo, G, Desando, I. Bartolotti & et al, "Scaffolds for Bone Tissue Engineering: State of the art and new perspectives", Materials Science and Engineering: C, vol. 78, pp. 1246-62, 2017.
[34] S. A. Hutchens, R. S. Benson, B. R. Evans, H. M. O’Neill & C. J. Rawn, "Biomimetic synthesis of calcium-deficient hydroxyapatite in a natural hydrogel", Biomaterials, vol. 27, pp. 4661-70, 2006.
[35] S. J. Kalita, A. Bhardwaj & H. A. Bhatt, "Nanocrystalline calcium phosphate ceramics in biomedical engineering", Materials Science and Engineering: C, vol. 27, 441-9, 2007.
[36] A. Amelian, K. Wasilewska, D. Megias & K. Winnicka, "Application of standard cell cultures and 3D in vitro tissue models as an effective tool in drug design and development", Pharmacological Reports, vol. 69, pp. 861-70, 2017.
[37] L. Nie, J. Suo, P. Zou & S. Feng, "Preparation and Properties of Biphasic Calcium Phosphate Scaffolds Multiply Coated with HA/PLLA Nanocomposites for Bone Tissue Engineering Applications", Journal of Nanomaterials, vol. 11, 2012.
[38] A. S. Hurtel-Lemaire, R. Mentaverri, A. Caudrillier, F. Cournarie, A. Wattel, S. Kamel & et al, "The calcium-sensing receptor is involved in strontium ranelate-induced osteoclast apoptosis, New insights into the associated signaling pathways", The Journal of biological chemistry, vol. 284, pp. 575-84, 2009.
[39] A. Bondarenko, N. Angrisani, A. Meyer-Lindenberg, J. M. Seitz, H, Waizy & J. Reifenrath, "Magnesium-based bone implants: immunohistochemical analysis of peri-implant osteogenesis by evaluation of osteopontin and osteocalcin expression", Journal of biomedical materials research Part A, vol. 102, pp. 1449-57, 2014.
[40] E. Landi, G. Logroscino, L, Proietti, A. Tampieri, M. Sandri & S. Sprio, "Biomimetic Mg-substituted hydroxyapatite: from synthesis to in vivo behavior", Journal of materials science Materials in medicine, vol. 19, pp. 239-47, 2008.
[41] Y. Yamasaki, Y. Yoshida, M. Okazaki, A. Shimazu, T. Kubo, Y. Akagawa & et al, "Action of FGMgCO3Ap-collagen composite in promoting bone formation", Biomaterials, vol. 24, pp. 4913-20, 2003.
[42] Y, Yamasaki, Y, Yoshida, M. Okazaki, A. Shimazu, T. Uchida, T. Kubo & et al, "Synthesis of functionally graded MgCO3 apatite accelerating osteoblast adhesion", J Biomed Mater Res, pp. 99-105, 2002.
[43] X. Li, K. Senda, A. Ito, Y. Sogo & A. Yamazaki, "Effect of Zn and Mg in tricalcium phosphate and in culture medium on apoptosis and actin ring formation of mature osteoclasts', Biomedical materials (Bristol, England), vol. 3, pp. 045002, 2008.
[44] W. Xue, J. L. Moore, H. L. Hosick, S. Bose, A. Bandyopadhyay, W. W. Lu & et al, "Osteoprecursor cell response to strontium-containing hydroxyapatite ceramics", Journal of Biomedical Materials Research Part A, vol. 79A, pp. 804-14, 2006.
[45] F. Tamimi, D. Le Nihouannen, D. C. Bassett, S. Ibasco, U. Gbureck, J. Knowles & et al, "Biocompatibility of magnesium phosphate minerals and their stability under physiological conditions", Acta Biomater, vol. 7, pp. 2678-85, 2011.
_||_