Synthesis and characterisation of nanophase hydroxyapatite co-substitutedwith strontium and zinc

Naomi Lowry, Mark Brolly, Yisong Han, Stephen McKillop, Brian Meenan, Adrian Boyd

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

In order to develop new bioactive calcium phosphate (CaP) materials to repair bone defects, it is important to ensure these materials more closely mimic the non-stoichiometric nature of biological hydroxyapatite (HA). Typically, biological HA combines various CaP phases with different impurity ions, which substitute within the HA lattice, including strontium (Sr2+), zinc (Zn2+), magnesium (Mg2+), carbonate (CO32-) and fluoride (F-), but to name a few. In addition to this biological HA have dimensions in the nanometre (nm) range, usually 60 nm in length by 5–20 nm wide. Both the effects of ion substitution and the nano-size crystals are seen as important factors for enhancing their potential biofunctionality. The driving hypothesis was to successfully synthesise nanoscale hydroxyapatite (nHA), co-substituted with strontium (Sr2+) and zinc (Zn2+) ions in varying oncentrations using an aqueous precipitation method and to understand their chemical and physical properties. The materials were characterised using Fourier Transform Infrared Spectroscopy (FTIR), X-Ray Diffraction (XRD), X-Ray Photoelectron Spectroscopy (XPS) and Transmission Electron Microscopy (TEM) techniques. The FTIR, XRD and XPS results confirmed that the nHA was successfully co-substituted with Sr2+ and Zn2+, replacing Ca2+ within the nHA lattice at varying concentrations. The FTIR results confirmed that all of the samples were carbonated, with a significant loss of hydroxylation as a consequence of the incorporation of Sr2+ and Zn2+ into the nHA lattice. The TEM results showed that each sample produced was nano-sized, with the Sr/Zn-10% nHA having the smallest sized crystals approximately 17.6±3.3 nm long and 10.2±1.4 nm wide. None of the materials synthesised here in this study contained any other impurity CaP phases. Therefore, this study has shown that co-substituted nHA can be prepared, and that the degree of substitution (and the substituting ion) can have a profound effect on the attendant materials’ properties.
LanguageEnglish
Pages7761-7770
JournalCeramics International
Volume44
Issue number7
Early online date4 Feb 2018
DOIs
Publication statusPublished - 31 May 2018

Fingerprint

Strontium
Durapatite
Zinc
Ions
X ray photoelectron spectroscopy
Impurities
Transmission electron microscopy
X ray diffraction
Hydroxylation
Crystals
Carbonates
Fluorides
Magnesium
Chemical properties
Materials properties
Bone
Repair
Physical properties
Defects

Keywords

  • Bioceramic
  • Nano-hydroxyapatite
  • Co-substitution
  • Strontium
  • Zinc

Cite this

@article{3470a2bdef8e42b380051197b8b98b53,
title = "Synthesis and characterisation of nanophase hydroxyapatite co-substitutedwith strontium and zinc",
abstract = "In order to develop new bioactive calcium phosphate (CaP) materials to repair bone defects, it is important to ensure these materials more closely mimic the non-stoichiometric nature of biological hydroxyapatite (HA). Typically, biological HA combines various CaP phases with different impurity ions, which substitute within the HA lattice, including strontium (Sr2+), zinc (Zn2+), magnesium (Mg2+), carbonate (CO32-) and fluoride (F-), but to name a few. In addition to this biological HA have dimensions in the nanometre (nm) range, usually 60 nm in length by 5–20 nm wide. Both the effects of ion substitution and the nano-size crystals are seen as important factors for enhancing their potential biofunctionality. The driving hypothesis was to successfully synthesise nanoscale hydroxyapatite (nHA), co-substituted with strontium (Sr2+) and zinc (Zn2+) ions in varying oncentrations using an aqueous precipitation method and to understand their chemical and physical properties. The materials were characterised using Fourier Transform Infrared Spectroscopy (FTIR), X-Ray Diffraction (XRD), X-Ray Photoelectron Spectroscopy (XPS) and Transmission Electron Microscopy (TEM) techniques. The FTIR, XRD and XPS results confirmed that the nHA was successfully co-substituted with Sr2+ and Zn2+, replacing Ca2+ within the nHA lattice at varying concentrations. The FTIR results confirmed that all of the samples were carbonated, with a significant loss of hydroxylation as a consequence of the incorporation of Sr2+ and Zn2+ into the nHA lattice. The TEM results showed that each sample produced was nano-sized, with the Sr/Zn-10{\%} nHA having the smallest sized crystals approximately 17.6±3.3 nm long and 10.2±1.4 nm wide. None of the materials synthesised here in this study contained any other impurity CaP phases. Therefore, this study has shown that co-substituted nHA can be prepared, and that the degree of substitution (and the substituting ion) can have a profound effect on the attendant materials’ properties.",
keywords = "Bioceramic, Nano-hydroxyapatite, Co-substitution, Strontium, Zinc",
author = "Naomi Lowry and Mark Brolly and Yisong Han and Stephen McKillop and Brian Meenan and Adrian Boyd",
note = "Compliant in UIR; evidence uploaded to 'Other files' Reference text: [1] K. Fox, P.A. Tran, N. Tran, Recent advances in research applications of nanophase hydroxyapatite, ChemPhysChem 13 (2012) 2495–2506, http://dx.doi.org/10. 1002/cphc.201200080. [2] H. Zhou, J. Lee, Nanoscale hydroxyapatite particles for bone tissue engineering, Acta Biomater. 7 (2011) 2769–2781, http://dx.doi.org/10.1016/j.actbio.2011.03. 019. [3] A. Siddharthan, S.K. Seshadri, T.S.S. Kumar, Rapid synthesis of calcium deficient hydroxyapatite nanoparticles by microwave irradiation, Trends Biomater. Artif. Organs 18 (2005) 110–113, http://dx.doi.org/10.1016/j.ssc.2004.02.045. [4] I.R. de Lima, G.G. Alves, C.A. Soriano, A.P. Campaneli, T.H. Gasparoto, E. Schnaider Ramos, L.{\'A}. de Sena, A.M. Rossi, J.M. Granjeiro, Understanding the impact of divalent cation substitution on hydroxyapatite: an in vitro multiparametric study on biocompatibility, J. Biomed. Mater. Res. Part A 98A (2011) 351–358, http://dx.doi. org/10.1002/jbm.a.33126. [5] 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 42 (2008) 129–138, http://dx.doi.org/10.1016/j.bone. 2007.08.043. [6] M. Roy, G.A. Fielding, A. Bandyopadhyay, S. Bose, Effects of zinc and strontium substitution in tricalcium phosphate on osteoclast differentiation and resorption, Biomater. Sci. (2013) 74–82, http://dx.doi.org/10.1039/c2bm00012a. [7] D.V. Shepherd, K. Kauppinen, R.A. Brooks, S.M. Best, An in vitro study into the effect of zinc substituted hydroxyapatite on osteoclast number and activity, J. Biomed. Mater. Res. – Part A 102 (2014) 4136–4141, http://dx.doi.org/10.1002/ jbm.a.35089. [8] J.H. Shepherd, D.V. Shepherd, S.M. Best, Substituted hydroxyapatites for bone repair, J. Mater. Sci. Mater. Med. 23 (2012) 2335–2347, http://dx.doi.org/10.1007/ s10856-012-4598-2. [9] V. Aina, L. Bergandi, G. Lusvardi, G. Malavasi, F.E. Imrie, I.R. Gibson, G. Cerrato, D. Ghigo, Sr-containing hydroxyapatite: morphologies of HA crystals and bioactivity on osteoblast cells, Mater. Sci. Eng. C 33 (2013) 1132–1142, http://dx.doi. org/10.1016/j.msec. 2012.12.005. [10] N. Lowry, Y. Han, B.J. Meenan, A.R. Boyd, Strontium and zinc co-substituted nanophase hydroxyapatite, Ceram. Int. 43 (2017) 12070–12078, http://dx.doi.org/ 10.1016/j.ceramint.2017.06.062. [11] L. Robinson, K. Salma-Ancane, L. Stipniece, B.J. Meenan, A.R. Boyd, The deposition of strontium and zinc Co-substituted hydroxyapatite coatings, J. Mater. Sci. Mater. Med. 28 (2017), http://dx.doi.org/10.1007/s10856-017-5846-2. [12] L. Tortet, J.R. Gavarri, G. Nihoul, Study of Protonic Mobility in CaHPO4·2H2O (Brushite) and CaHPO4 (Monetite) By Infrared Spectroscopy and Neutron Scattering, 16, 1997, pp. 6–16. [13] A.R. Boyd, C. O’Kane, B.J. Meenan, Control of calcium phosphate thin film stoichiometry using multi-target sputter deposition, Surf. Coat. Technol. 233 (2013) 131–139, http://dx.doi.org/10.1016/j.surfcoat.2013.04.017. [14] C.-J. Chung, H.-Y. Long, Systematic strontium substitution in hydroxyapatite coatings on titanium via micro-arc treatment and their osteoblast/osteoclast responses, Acta Biomater. 7 (2011) 4081–4087, http://dx.doi.org/10.1016/j.actbio. 2011.07.004. [15] A.R. Boyd, B.J. Meenan, N.S. Leyland, Surface characterisation of the evolving nature of radio frequency (RF) magnetron sputter deposited calcium phosphate thin films after exposure to physiological solution, Surf. Coat. Technol. 200 (2006) 6002–6013, http://dx.doi.org/10.1016/j.surfcoat.2005.09.032. [16] I.R. Gibson, W. Bonfield, Novel synthesis and characterization of an AB-type carbonate- substituted hydroxyapatite, J. Biomed. Mater. Res. 59 (2002) 697–708, http://dx.doi.org/10.1002/jbm.10044. [17] A.R. Boyd, L. Rutledge, L.D. Randolph, B.J. Meenan, Strontium-substituted hydroxyapatite coatings deposited via a co-deposition sputter technique, Mater. Sci. Eng. C 46 (2015) 290–300, http://dx.doi.org/10.1016/j.msec. 2014.10.046. [18] A. Costescu, I. Pasuk, F. Ungureanu, A. Dinischiotu, F. Huneau, S. Galaup, P.L.E. Coustumer, D. Predoi, C. Ftir, Physico-Chemical Properties of Nano-Sized Hexagonal Hydroxyapatite Powder Synthesized by Sol-Gel, 5, 2010, pp. 89–1000. [19] A.R. Boyd, L. Rutledge, L.D. Randolph, I. Mutreja, B.J. Meenan, The deposition of strontium-substituted hydroxyapatite coatings, J. Mater. Sci. Mater. Med. 26 (2015) 65, http://dx.doi.org/10.1007/s10856-014-5377-z. [20] W. Xia, C. Lindahl, C. Persson, P. Thomsen, J. Lausmaa, H. Engqvist, Changes of Surface Composition and Morphology after Incorporation of Ions into Biomimetic Apatite Coatings, 2010, 2010, pp. 7–16. ⟨https://dx.doi.org/10.4236/jbnb.2010. 11002⟩. [21] Y. Zhao, D. Guo, S. Hou, H. Zhong, J. Yan, C. Zhang, Y. Zhou, Porous Allograft Bone Scaffolds: Doping with Strontium, 8, 2013, pp. 1–10. ⟨https://dx.doi.org/10.1371/ journal.pone.0069339⟩. [22] Y.Y. {\"O}zbek, F.E. Baştan, F. {\"U}stel, Synthesis and characterization of strontium-doped hydroxyapatite for biomedical applications, J. Therm. Anal. Calorim. 125 (2016) 745–750, http://dx.doi.org/10.1007/s10973-016-5607-3. [23] L. Li, X. Lu, Y. Meng, C.M. Weyant, Comparison study of biomimetic strontiumdoped calcium phosphate coatings by electrochemical deposition and air plasma spray: morphology, composition and bioactive performance, J. Mater. Sci. Mater. Med. 23 (2012) 2359–2368, http://dx.doi.org/10.1007/s10856-012-4633-3. [24] A. Anwar, S. Akbar, A. Sadiqa, M. Kazmi, Novel continuous flow synthesis, characterization and antibacterial studies of nanoscale zinc substituted hydroxyapatite bioceramics, Inorg. Chim. Acta 453 (2016) 16–22, http://dx.doi.org/10.1016/j.ica. 2016.07.041. [25] I. Pereiro, C. Rodriguez-Valencia, C. Serr, C. Solla, J. Serra, P. Gonzalez, Structural properties of ZnO films grown by picosecond pulsed-laser deposition, Appl. Surf. Sci. 258 (2012) 9192–9197. [26] M. Kavitha, R. Subramanian, R. Narayanan, V. Udhayabanu, Solution combustion synthesis and characterization of strontium substituted hydroxyapatite nanocrystals, Powder Technol. 253 (2014) 129–137, http://dx.doi.org/10.1016/j.powtec. 2013.10.045. [27] V. Krishnan, A. Bhatia, H. Varma, Development, characterization and comparison of two strontium doped nano hydroxyapatite molecules for enamel repair / regeneration, Dent. Mater. 32 (2016) 646–659, http://dx.doi.org/10.1016/j.dental. 2016.02.002. [28] K.P. Tank, P. Sharma, D.K. Kanchan, M.J. Joshi, FTIR, Powder XRD, TEM and Dielectric Studies of Pure and Zinc Doped Nano-Hydroxyapatite, 1316, 2011, pp. 1309–1316. ⟨https://dx.doi.org/10.1002/crat.201100080⟩. [29] S.V. Dorozhkin, Nanosized and nanocrystalline calcium orthophosphates, Acta Biomater. 6 (2010) 715–734, http://dx.doi.org/10.1016/j.actbio.2009.10.031. [30] H. Zreiqat, Y. Ramaswamy, C. Wu, A. Paschalidis, Z. Lu, B. James, O. Birke, M. McDonald, D. Little, C.R. Dunstan, The incorporation of strontium and zinc into a calcium–silicon ceramic for bone tissue engineering, Biomaterials 31 (2010) 3175–3184, http://dx.doi.org/10.1016/j.biomaterials.2010.01.024. [31] V. Mourino, J.P. Cattalini, A.R. Boccaccini, Metallic ions as therapeutic agents in tissue engineering scaffolds: an overview of their biological applications and strategies for new developments, J. R. Soc. Interface 9 (2012) 401–419, http://dx.doi. org/10.1098/rsif.2011.0611. N. Lowry et al. Ceramics International xxx (xxxx) xxx–xxx 9 [32] F. Yang, D. Yang, J. Tu, Q. Zheng, L. Cai, L. Wang, Strontium enhances osteogenic differentiation of mesenchymal stem cells and in vivo bone formation by activating Wnt/catenin signaling, Stem Cells (2011), http://dx.doi.org/10.1002/stem.646. [33] T. Kubota, T. Michigami, K. Ozono, Wnt signaling in bone metabolism, J. Bone Miner. Metab. 27 (2009) 265–271, http://dx.doi.org/10.1007/s00774-009-0064-8. [34] M. Arioka, F. Takahashi-Yanaga, M. Sasaki, T. Yoshihara, S. Morimoto, M. Hirata, Y. Mori, T. Sasaguri, Acceleration of bone regeneration by local application of lithium: Wnt signal-mediated osteoblastogenesis and Wnt signal-independent suppression of osteoclastogenesis, Biochem. Pharmacol. 90 (2014) 397–405, http://dx. doi.org/10.1016/j.bcp.2014.06.011. [35] S.C. Cox, P. Jamshidi, L.M. Grover, K.K. Mallick, Preparation and characterisation of nanophase Sr, Mg, and Zn substituted hydroxyapatite by aqueous precipitation, Mater. Sci. Eng. C 35 (2014) 106–114, http://dx.doi.org/10.1016/j.msec. 2013.10. 015. [36] F. Ren, R. Xin, X. Ge, Y. Leng, Characterization and structural analysis of zincsubstituted hydroxyapatites, Acta Biomater. 5 (2009) 3141–3149, http://dx.doi. org/10.1016/j.actbio.2009.04.014. [37] H. Storrie, S.I. Stupp, Cellular Response to Zinc-Containing Organoapatite: An In Vitro Study of Proliferation, Alkaline Phosphatase Activity and Biomineralization, 26, 2005, pp. 5492–5499. ⟨https://dx.doi.org/10.1016/j.biomaterials.2005.01. 043⟩. [38] G.S. Kumar, A. Thamizhavel, Y. Yokogawa, S.N. Kalkura, E.K. Girija, Synthesis, characterization and in vitro studies of zinc and carbonate co-substituted nanohydroxyapatite for biomedical applications, Mater. Chem. Phys. 134 (2012) 1127–1135, http://dx.doi.org/10.1016/j.matchemphys.2012.04.005. [39] R.J. Friederichs, H.F. Chappell, D.V. Shepherd, S.M. Best, Synthesis, characterization and modelling of zinc and silicate co-substituted hydroxyapatite, J. R. Soc. Interface 12 (2015) 20150190, http://dx.doi.org/10.1098/rsif.2015.0190. [40] L. Stipniece, K. Salma-Ancane, N. Borodajenko, M. Sokolova, D. Jakovlevs, L. Berzina-Cimdina, Characterization of Mg-substituted hydroxyapatite synthesized by wet chemical method, Ceram. Int. 40 (2014) 3261–3267, http://dx.doi.org/10. 1016/j.ceramint.2013.09.110. [41] M. Vandrovcova, T.E.L. Douglas, W. Mr{\'o}z, O. Musial, D. Schaubroeck, B. Budner, R. Syroka, P. Dubruel, L. Bacakova, Pulsed laser deposition of magnesium-doped calcium phosphate coatings on porous polycaprolactone scaffolds produced by rapid prototyping, Mater. Lett. 148 (2015) 178–183, http://dx.doi.org/10.1016/j. matlet.2015.02.074. [42] K. Salma-Ancane, L. Stipniece, A. Putnins, L. Berzina-Cimdina, Development of Mgcontaining porous β-tricalcium phosphate scaffolds for bone repair, Ceram. Int. 41 (2015) 4996–5004, http://dx.doi.org/10.1016/j.ceramint.2014.12.065. [43] G.A. Fielding, M. Roy, A. Bandyopadhyay, S. Bose, Antibacterial and biological characteristics of silver containing and strontium doped plasma sprayed hydroxyapatite coatings, Acta Biomater. 8 (2012) 3144–3152, http://dx.doi.org/10. 1016/j.actbio.2012.04.004. [44] A. Zamani, G.R. Omrani, M.M. Nasab, Lithium's effect on bone mineral density, Bone 44 (2009) 331–334, http://dx.doi.org/10.1016/j.bone.2008.10.001. [45] H.D. Jang, J.H. Shin, D.R. Park, J.H. Hong, K. Yoon, R. Ko, C.Y. Ko, H.S. Kim, D. Jeong, N. Kim, S.Y. Lee, Inactivation of glycogen synthase kinase-3?? Is required for osteoclast differentiation, J. Biol. Chem. 286 (2011) 39043–39050, http://dx. doi.org/10.1074/jbc.M111.256768. [46] J. Albers, J. Keller, A. Baranowsky, F.T. Beil, P. Catala-Lehnen, J. Schulze, M. Amling, T. Schinke, Canonical Wnt signaling inhibits osteoclastogenesis independent of osteoprotegerin, J. Cell Biol. 200 (2013) 537–549, http://dx.doi.org/ 10.1083/jcb.201207142. [47] W. Wei, D. Zeve, J.M. Suh, X. Wang, Y. Du, J.E. Zerwekh, P.C. Dechow, J.M. Graff, Y. Wan, Biphasic and dosage-dependent regulation of osteoclastogenesis by -catenin, Mol. Cell. Biol. 31 (2011) 4706–4719, http://dx.doi.org/10.1128/MCB. 05980-11. [48] V. Stanic, S. Dimitrijevic, J. Antic-Stankovic, M. Mitric, B. Jokic, I.B. Plecac, S. Raicevic, Synthesis, characterization and antimicrobial activity of copper and zinc-doped hydroxyapatite nanopowders, Appl. Surf. Sci. 256 (2010) 6083–6089, http://dx.doi.org/10.1016/j.apsusc.2010.03.124. [49] W.-L. Du, Y.-L. Xu, Z.-R. Xu, C.-L. Fan, Preparation, characterization and antibacterial properties against E. coli K(88) of chitosan nanoparticle loaded copper ions, Nanotechnology 19 (2008) 85707, http://dx.doi.org/10.1088/0957-4484/ 19/8/085707. [50] R.J. Friederichs, R.A. Brooks, M. Ueda, S.M. Best, In vitro osteoclast formation and resorption of silicon-substituted hydroxyapatite ceramics, J. Biomed. Mater. Res. – Part A 103 (2015) 3312–3322, http://dx.doi.org/10.1002/jbm.a.35470. [51] D.M. Reffitt, N. Ogston, R. Jugdaohsingh, H.F.J. Cheung, B.A.J. Evans, R.P.H. Thompson, J.J. Powell, G.N. Hampson, Orthosilicic Acid Stimulates Collagen Type 1 Synthesis and Osteoblastic Differentiation in Human Osteoblast-Like Cells In Vitro, 32, 2003, pp. 127–135. ⟨https://dx.doi.org/10.1016/S8756-3282(02) 00950-X⟩. [52] R. Ferro De Godoy, S. Hutchens, C. Campion, G. Blunn, Silicate-substituted calcium phosphate with enhanced strut porosity stimulates osteogenic differentiation of human mesenchymal stem cells, J. Mater. Sci. Mater. Med. 26 (2015) 5387, http:// dx.doi.org/10.1007/s10856-015-5387-5. [53] J.C. Merry, I.R. Gibson, S.M. Best, W. Bonfield, Synthesis and characterization of carbonate hydroxyapatite, J. Mater. Sci. Mater. Med. 9 (1998) 779–783, http://dx. doi.org/10.1023/A:1008975507498. [54] V. Stanic, S. Dimitrijevic, D.G. Antonovic, B.M. Jokic, S.P. Zec, S.T. Tanaskovic, S. Raicevicc, Synthesis of fluorine substituted hydroxyapatite nanopowders and application of the central composite design for determination of its antimicrobial effects, Appl. Surf. Sci. 290 (2014) 346–352, http://dx.doi.org/10.1016/j.apsusc. 2013.11.081. N. Lowry et al. Ceramics International xxx (xxxx) xxx–xxx 10",
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Synthesis and characterisation of nanophase hydroxyapatite co-substitutedwith strontium and zinc. / Lowry, Naomi; Brolly, Mark; Han, Yisong; McKillop, Stephen; Meenan, Brian; Boyd, Adrian.

In: Ceramics International, Vol. 44, No. 7, 31.05.2018, p. 7761-7770.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Synthesis and characterisation of nanophase hydroxyapatite co-substitutedwith strontium and zinc

AU - Lowry, Naomi

AU - Brolly, Mark

AU - Han, Yisong

AU - McKillop, Stephen

AU - Meenan, Brian

AU - Boyd, Adrian

N1 - Compliant in UIR; evidence uploaded to 'Other files' Reference text: [1] K. Fox, P.A. Tran, N. Tran, Recent advances in research applications of nanophase hydroxyapatite, ChemPhysChem 13 (2012) 2495–2506, http://dx.doi.org/10. 1002/cphc.201200080. [2] H. Zhou, J. Lee, Nanoscale hydroxyapatite particles for bone tissue engineering, Acta Biomater. 7 (2011) 2769–2781, http://dx.doi.org/10.1016/j.actbio.2011.03. 019. [3] A. Siddharthan, S.K. Seshadri, T.S.S. Kumar, Rapid synthesis of calcium deficient hydroxyapatite nanoparticles by microwave irradiation, Trends Biomater. Artif. Organs 18 (2005) 110–113, http://dx.doi.org/10.1016/j.ssc.2004.02.045. [4] I.R. de Lima, G.G. Alves, C.A. Soriano, A.P. Campaneli, T.H. Gasparoto, E. Schnaider Ramos, L.Á. de Sena, A.M. Rossi, J.M. Granjeiro, Understanding the impact of divalent cation substitution on hydroxyapatite: an in vitro multiparametric study on biocompatibility, J. Biomed. Mater. Res. Part A 98A (2011) 351–358, http://dx.doi. org/10.1002/jbm.a.33126. [5] 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 42 (2008) 129–138, http://dx.doi.org/10.1016/j.bone. 2007.08.043. [6] M. Roy, G.A. Fielding, A. Bandyopadhyay, S. Bose, Effects of zinc and strontium substitution in tricalcium phosphate on osteoclast differentiation and resorption, Biomater. Sci. (2013) 74–82, http://dx.doi.org/10.1039/c2bm00012a. [7] D.V. Shepherd, K. Kauppinen, R.A. Brooks, S.M. Best, An in vitro study into the effect of zinc substituted hydroxyapatite on osteoclast number and activity, J. Biomed. Mater. Res. – Part A 102 (2014) 4136–4141, http://dx.doi.org/10.1002/ jbm.a.35089. [8] J.H. Shepherd, D.V. Shepherd, S.M. Best, Substituted hydroxyapatites for bone repair, J. Mater. Sci. Mater. Med. 23 (2012) 2335–2347, http://dx.doi.org/10.1007/ s10856-012-4598-2. [9] V. Aina, L. Bergandi, G. Lusvardi, G. Malavasi, F.E. Imrie, I.R. Gibson, G. Cerrato, D. Ghigo, Sr-containing hydroxyapatite: morphologies of HA crystals and bioactivity on osteoblast cells, Mater. Sci. Eng. C 33 (2013) 1132–1142, http://dx.doi. org/10.1016/j.msec. 2012.12.005. [10] N. Lowry, Y. Han, B.J. Meenan, A.R. Boyd, Strontium and zinc co-substituted nanophase hydroxyapatite, Ceram. Int. 43 (2017) 12070–12078, http://dx.doi.org/ 10.1016/j.ceramint.2017.06.062. [11] L. Robinson, K. Salma-Ancane, L. Stipniece, B.J. Meenan, A.R. Boyd, The deposition of strontium and zinc Co-substituted hydroxyapatite coatings, J. Mater. Sci. Mater. Med. 28 (2017), http://dx.doi.org/10.1007/s10856-017-5846-2. [12] L. Tortet, J.R. Gavarri, G. Nihoul, Study of Protonic Mobility in CaHPO4·2H2O (Brushite) and CaHPO4 (Monetite) By Infrared Spectroscopy and Neutron Scattering, 16, 1997, pp. 6–16. [13] A.R. Boyd, C. O’Kane, B.J. Meenan, Control of calcium phosphate thin film stoichiometry using multi-target sputter deposition, Surf. Coat. Technol. 233 (2013) 131–139, http://dx.doi.org/10.1016/j.surfcoat.2013.04.017. [14] C.-J. Chung, H.-Y. Long, Systematic strontium substitution in hydroxyapatite coatings on titanium via micro-arc treatment and their osteoblast/osteoclast responses, Acta Biomater. 7 (2011) 4081–4087, http://dx.doi.org/10.1016/j.actbio. 2011.07.004. [15] A.R. Boyd, B.J. Meenan, N.S. Leyland, Surface characterisation of the evolving nature of radio frequency (RF) magnetron sputter deposited calcium phosphate thin films after exposure to physiological solution, Surf. Coat. Technol. 200 (2006) 6002–6013, http://dx.doi.org/10.1016/j.surfcoat.2005.09.032. [16] I.R. Gibson, W. Bonfield, Novel synthesis and characterization of an AB-type carbonate- substituted hydroxyapatite, J. Biomed. Mater. Res. 59 (2002) 697–708, http://dx.doi.org/10.1002/jbm.10044. [17] A.R. Boyd, L. Rutledge, L.D. Randolph, B.J. Meenan, Strontium-substituted hydroxyapatite coatings deposited via a co-deposition sputter technique, Mater. Sci. Eng. C 46 (2015) 290–300, http://dx.doi.org/10.1016/j.msec. 2014.10.046. [18] A. Costescu, I. Pasuk, F. Ungureanu, A. Dinischiotu, F. Huneau, S. Galaup, P.L.E. Coustumer, D. Predoi, C. Ftir, Physico-Chemical Properties of Nano-Sized Hexagonal Hydroxyapatite Powder Synthesized by Sol-Gel, 5, 2010, pp. 89–1000. [19] A.R. Boyd, L. Rutledge, L.D. Randolph, I. Mutreja, B.J. Meenan, The deposition of strontium-substituted hydroxyapatite coatings, J. Mater. Sci. Mater. Med. 26 (2015) 65, http://dx.doi.org/10.1007/s10856-014-5377-z. [20] W. Xia, C. Lindahl, C. Persson, P. Thomsen, J. Lausmaa, H. Engqvist, Changes of Surface Composition and Morphology after Incorporation of Ions into Biomimetic Apatite Coatings, 2010, 2010, pp. 7–16. ⟨https://dx.doi.org/10.4236/jbnb.2010. 11002⟩. [21] Y. Zhao, D. Guo, S. Hou, H. Zhong, J. Yan, C. Zhang, Y. Zhou, Porous Allograft Bone Scaffolds: Doping with Strontium, 8, 2013, pp. 1–10. ⟨https://dx.doi.org/10.1371/ journal.pone.0069339⟩. [22] Y.Y. Özbek, F.E. Baştan, F. Üstel, Synthesis and characterization of strontium-doped hydroxyapatite for biomedical applications, J. Therm. Anal. Calorim. 125 (2016) 745–750, http://dx.doi.org/10.1007/s10973-016-5607-3. [23] L. Li, X. Lu, Y. Meng, C.M. Weyant, Comparison study of biomimetic strontiumdoped calcium phosphate coatings by electrochemical deposition and air plasma spray: morphology, composition and bioactive performance, J. Mater. Sci. Mater. Med. 23 (2012) 2359–2368, http://dx.doi.org/10.1007/s10856-012-4633-3. [24] A. Anwar, S. Akbar, A. Sadiqa, M. Kazmi, Novel continuous flow synthesis, characterization and antibacterial studies of nanoscale zinc substituted hydroxyapatite bioceramics, Inorg. Chim. Acta 453 (2016) 16–22, http://dx.doi.org/10.1016/j.ica. 2016.07.041. [25] I. Pereiro, C. Rodriguez-Valencia, C. Serr, C. Solla, J. Serra, P. Gonzalez, Structural properties of ZnO films grown by picosecond pulsed-laser deposition, Appl. Surf. Sci. 258 (2012) 9192–9197. [26] M. Kavitha, R. Subramanian, R. Narayanan, V. Udhayabanu, Solution combustion synthesis and characterization of strontium substituted hydroxyapatite nanocrystals, Powder Technol. 253 (2014) 129–137, http://dx.doi.org/10.1016/j.powtec. 2013.10.045. [27] V. Krishnan, A. Bhatia, H. Varma, Development, characterization and comparison of two strontium doped nano hydroxyapatite molecules for enamel repair / regeneration, Dent. Mater. 32 (2016) 646–659, http://dx.doi.org/10.1016/j.dental. 2016.02.002. [28] K.P. Tank, P. Sharma, D.K. Kanchan, M.J. Joshi, FTIR, Powder XRD, TEM and Dielectric Studies of Pure and Zinc Doped Nano-Hydroxyapatite, 1316, 2011, pp. 1309–1316. ⟨https://dx.doi.org/10.1002/crat.201100080⟩. [29] S.V. Dorozhkin, Nanosized and nanocrystalline calcium orthophosphates, Acta Biomater. 6 (2010) 715–734, http://dx.doi.org/10.1016/j.actbio.2009.10.031. [30] H. Zreiqat, Y. Ramaswamy, C. Wu, A. Paschalidis, Z. Lu, B. James, O. Birke, M. McDonald, D. Little, C.R. Dunstan, The incorporation of strontium and zinc into a calcium–silicon ceramic for bone tissue engineering, Biomaterials 31 (2010) 3175–3184, http://dx.doi.org/10.1016/j.biomaterials.2010.01.024. [31] V. Mourino, J.P. Cattalini, A.R. Boccaccini, Metallic ions as therapeutic agents in tissue engineering scaffolds: an overview of their biological applications and strategies for new developments, J. R. Soc. Interface 9 (2012) 401–419, http://dx.doi. org/10.1098/rsif.2011.0611. N. Lowry et al. Ceramics International xxx (xxxx) xxx–xxx 9 [32] F. Yang, D. Yang, J. Tu, Q. Zheng, L. Cai, L. Wang, Strontium enhances osteogenic differentiation of mesenchymal stem cells and in vivo bone formation by activating Wnt/catenin signaling, Stem Cells (2011), http://dx.doi.org/10.1002/stem.646. [33] T. Kubota, T. Michigami, K. Ozono, Wnt signaling in bone metabolism, J. Bone Miner. Metab. 27 (2009) 265–271, http://dx.doi.org/10.1007/s00774-009-0064-8. [34] M. Arioka, F. Takahashi-Yanaga, M. Sasaki, T. Yoshihara, S. Morimoto, M. Hirata, Y. Mori, T. Sasaguri, Acceleration of bone regeneration by local application of lithium: Wnt signal-mediated osteoblastogenesis and Wnt signal-independent suppression of osteoclastogenesis, Biochem. Pharmacol. 90 (2014) 397–405, http://dx. doi.org/10.1016/j.bcp.2014.06.011. [35] S.C. Cox, P. Jamshidi, L.M. Grover, K.K. Mallick, Preparation and characterisation of nanophase Sr, Mg, and Zn substituted hydroxyapatite by aqueous precipitation, Mater. Sci. Eng. C 35 (2014) 106–114, http://dx.doi.org/10.1016/j.msec. 2013.10. 015. [36] F. Ren, R. Xin, X. Ge, Y. Leng, Characterization and structural analysis of zincsubstituted hydroxyapatites, Acta Biomater. 5 (2009) 3141–3149, http://dx.doi. org/10.1016/j.actbio.2009.04.014. [37] H. Storrie, S.I. Stupp, Cellular Response to Zinc-Containing Organoapatite: An In Vitro Study of Proliferation, Alkaline Phosphatase Activity and Biomineralization, 26, 2005, pp. 5492–5499. ⟨https://dx.doi.org/10.1016/j.biomaterials.2005.01. 043⟩. [38] G.S. Kumar, A. Thamizhavel, Y. Yokogawa, S.N. Kalkura, E.K. Girija, Synthesis, characterization and in vitro studies of zinc and carbonate co-substituted nanohydroxyapatite for biomedical applications, Mater. Chem. Phys. 134 (2012) 1127–1135, http://dx.doi.org/10.1016/j.matchemphys.2012.04.005. [39] R.J. Friederichs, H.F. Chappell, D.V. Shepherd, S.M. Best, Synthesis, characterization and modelling of zinc and silicate co-substituted hydroxyapatite, J. R. Soc. Interface 12 (2015) 20150190, http://dx.doi.org/10.1098/rsif.2015.0190. [40] L. Stipniece, K. Salma-Ancane, N. Borodajenko, M. Sokolova, D. Jakovlevs, L. Berzina-Cimdina, Characterization of Mg-substituted hydroxyapatite synthesized by wet chemical method, Ceram. Int. 40 (2014) 3261–3267, http://dx.doi.org/10. 1016/j.ceramint.2013.09.110. [41] M. Vandrovcova, T.E.L. Douglas, W. Mróz, O. Musial, D. Schaubroeck, B. Budner, R. Syroka, P. Dubruel, L. Bacakova, Pulsed laser deposition of magnesium-doped calcium phosphate coatings on porous polycaprolactone scaffolds produced by rapid prototyping, Mater. Lett. 148 (2015) 178–183, http://dx.doi.org/10.1016/j. matlet.2015.02.074. [42] K. Salma-Ancane, L. Stipniece, A. Putnins, L. Berzina-Cimdina, Development of Mgcontaining porous β-tricalcium phosphate scaffolds for bone repair, Ceram. Int. 41 (2015) 4996–5004, http://dx.doi.org/10.1016/j.ceramint.2014.12.065. [43] G.A. Fielding, M. Roy, A. Bandyopadhyay, S. Bose, Antibacterial and biological characteristics of silver containing and strontium doped plasma sprayed hydroxyapatite coatings, Acta Biomater. 8 (2012) 3144–3152, http://dx.doi.org/10. 1016/j.actbio.2012.04.004. [44] A. Zamani, G.R. Omrani, M.M. Nasab, Lithium's effect on bone mineral density, Bone 44 (2009) 331–334, http://dx.doi.org/10.1016/j.bone.2008.10.001. [45] H.D. Jang, J.H. Shin, D.R. Park, J.H. Hong, K. Yoon, R. Ko, C.Y. Ko, H.S. Kim, D. Jeong, N. Kim, S.Y. Lee, Inactivation of glycogen synthase kinase-3?? Is required for osteoclast differentiation, J. Biol. Chem. 286 (2011) 39043–39050, http://dx. doi.org/10.1074/jbc.M111.256768. [46] J. Albers, J. Keller, A. Baranowsky, F.T. Beil, P. Catala-Lehnen, J. Schulze, M. Amling, T. Schinke, Canonical Wnt signaling inhibits osteoclastogenesis independent of osteoprotegerin, J. Cell Biol. 200 (2013) 537–549, http://dx.doi.org/ 10.1083/jcb.201207142. [47] W. Wei, D. Zeve, J.M. Suh, X. Wang, Y. Du, J.E. Zerwekh, P.C. Dechow, J.M. Graff, Y. Wan, Biphasic and dosage-dependent regulation of osteoclastogenesis by -catenin, Mol. Cell. Biol. 31 (2011) 4706–4719, http://dx.doi.org/10.1128/MCB. 05980-11. [48] V. Stanic, S. Dimitrijevic, J. Antic-Stankovic, M. Mitric, B. Jokic, I.B. Plecac, S. Raicevic, Synthesis, characterization and antimicrobial activity of copper and zinc-doped hydroxyapatite nanopowders, Appl. Surf. Sci. 256 (2010) 6083–6089, http://dx.doi.org/10.1016/j.apsusc.2010.03.124. [49] W.-L. Du, Y.-L. Xu, Z.-R. Xu, C.-L. Fan, Preparation, characterization and antibacterial properties against E. coli K(88) of chitosan nanoparticle loaded copper ions, Nanotechnology 19 (2008) 85707, http://dx.doi.org/10.1088/0957-4484/ 19/8/085707. [50] R.J. Friederichs, R.A. Brooks, M. Ueda, S.M. Best, In vitro osteoclast formation and resorption of silicon-substituted hydroxyapatite ceramics, J. Biomed. Mater. Res. – Part A 103 (2015) 3312–3322, http://dx.doi.org/10.1002/jbm.a.35470. [51] D.M. Reffitt, N. Ogston, R. Jugdaohsingh, H.F.J. Cheung, B.A.J. Evans, R.P.H. Thompson, J.J. Powell, G.N. Hampson, Orthosilicic Acid Stimulates Collagen Type 1 Synthesis and Osteoblastic Differentiation in Human Osteoblast-Like Cells In Vitro, 32, 2003, pp. 127–135. ⟨https://dx.doi.org/10.1016/S8756-3282(02) 00950-X⟩. [52] R. Ferro De Godoy, S. Hutchens, C. Campion, G. Blunn, Silicate-substituted calcium phosphate with enhanced strut porosity stimulates osteogenic differentiation of human mesenchymal stem cells, J. Mater. Sci. Mater. Med. 26 (2015) 5387, http:// dx.doi.org/10.1007/s10856-015-5387-5. [53] J.C. Merry, I.R. Gibson, S.M. Best, W. Bonfield, Synthesis and characterization of carbonate hydroxyapatite, J. Mater. Sci. Mater. Med. 9 (1998) 779–783, http://dx. doi.org/10.1023/A:1008975507498. [54] V. Stanic, S. Dimitrijevic, D.G. Antonovic, B.M. Jokic, S.P. Zec, S.T. Tanaskovic, S. Raicevicc, Synthesis of fluorine substituted hydroxyapatite nanopowders and application of the central composite design for determination of its antimicrobial effects, Appl. Surf. Sci. 290 (2014) 346–352, http://dx.doi.org/10.1016/j.apsusc. 2013.11.081. N. Lowry et al. Ceramics International xxx (xxxx) xxx–xxx 10

PY - 2018/5/31

Y1 - 2018/5/31

N2 - In order to develop new bioactive calcium phosphate (CaP) materials to repair bone defects, it is important to ensure these materials more closely mimic the non-stoichiometric nature of biological hydroxyapatite (HA). Typically, biological HA combines various CaP phases with different impurity ions, which substitute within the HA lattice, including strontium (Sr2+), zinc (Zn2+), magnesium (Mg2+), carbonate (CO32-) and fluoride (F-), but to name a few. In addition to this biological HA have dimensions in the nanometre (nm) range, usually 60 nm in length by 5–20 nm wide. Both the effects of ion substitution and the nano-size crystals are seen as important factors for enhancing their potential biofunctionality. The driving hypothesis was to successfully synthesise nanoscale hydroxyapatite (nHA), co-substituted with strontium (Sr2+) and zinc (Zn2+) ions in varying oncentrations using an aqueous precipitation method and to understand their chemical and physical properties. The materials were characterised using Fourier Transform Infrared Spectroscopy (FTIR), X-Ray Diffraction (XRD), X-Ray Photoelectron Spectroscopy (XPS) and Transmission Electron Microscopy (TEM) techniques. The FTIR, XRD and XPS results confirmed that the nHA was successfully co-substituted with Sr2+ and Zn2+, replacing Ca2+ within the nHA lattice at varying concentrations. The FTIR results confirmed that all of the samples were carbonated, with a significant loss of hydroxylation as a consequence of the incorporation of Sr2+ and Zn2+ into the nHA lattice. The TEM results showed that each sample produced was nano-sized, with the Sr/Zn-10% nHA having the smallest sized crystals approximately 17.6±3.3 nm long and 10.2±1.4 nm wide. None of the materials synthesised here in this study contained any other impurity CaP phases. Therefore, this study has shown that co-substituted nHA can be prepared, and that the degree of substitution (and the substituting ion) can have a profound effect on the attendant materials’ properties.

AB - In order to develop new bioactive calcium phosphate (CaP) materials to repair bone defects, it is important to ensure these materials more closely mimic the non-stoichiometric nature of biological hydroxyapatite (HA). Typically, biological HA combines various CaP phases with different impurity ions, which substitute within the HA lattice, including strontium (Sr2+), zinc (Zn2+), magnesium (Mg2+), carbonate (CO32-) and fluoride (F-), but to name a few. In addition to this biological HA have dimensions in the nanometre (nm) range, usually 60 nm in length by 5–20 nm wide. Both the effects of ion substitution and the nano-size crystals are seen as important factors for enhancing their potential biofunctionality. The driving hypothesis was to successfully synthesise nanoscale hydroxyapatite (nHA), co-substituted with strontium (Sr2+) and zinc (Zn2+) ions in varying oncentrations using an aqueous precipitation method and to understand their chemical and physical properties. The materials were characterised using Fourier Transform Infrared Spectroscopy (FTIR), X-Ray Diffraction (XRD), X-Ray Photoelectron Spectroscopy (XPS) and Transmission Electron Microscopy (TEM) techniques. The FTIR, XRD and XPS results confirmed that the nHA was successfully co-substituted with Sr2+ and Zn2+, replacing Ca2+ within the nHA lattice at varying concentrations. The FTIR results confirmed that all of the samples were carbonated, with a significant loss of hydroxylation as a consequence of the incorporation of Sr2+ and Zn2+ into the nHA lattice. The TEM results showed that each sample produced was nano-sized, with the Sr/Zn-10% nHA having the smallest sized crystals approximately 17.6±3.3 nm long and 10.2±1.4 nm wide. None of the materials synthesised here in this study contained any other impurity CaP phases. Therefore, this study has shown that co-substituted nHA can be prepared, and that the degree of substitution (and the substituting ion) can have a profound effect on the attendant materials’ properties.

KW - Bioceramic

KW - Nano-hydroxyapatite

KW - Co-substitution

KW - Strontium

KW - Zinc

UR - https://www.sciencedirect.com/science/article/pii/S0272884218302190

U2 - 10.1016/j.ceramint.2018.01.206

DO - 10.1016/j.ceramint.2018.01.206

M3 - Article

VL - 44

SP - 7761

EP - 7770

JO - Ceramics International

T2 - Ceramics International

JF - Ceramics International

SN - 0272-8842

IS - 7

ER -