bone repair applications; cell proliferation; copper; coprecipitation synthesis; cytocompatibility; doping; hardness; magnesium; silver; sintering; strontium; β-TCP; Ag +; Bone repair; Bone repair application; Co-doped; Coprecipitation synthesis; Cytocompatibility; Mechanical; Repair applications; Tri-calcium phosphates; Ceramics and Composites; Materials Chemistry
Abstract :
[en] β-tricalcium phosphate (β-TCP, β-Ca3(PO4)2) is an attractive biomaterial for bone repair applications. However, its sintering and mechanical properties are limited by a problematic phase transition to α-TCP. Cationic doping of β-TCP is able to postpone the formation of α-TCP allowing higher sintering temperatures and better mechanical properties. The co-doping of β-TCP with Mg2+ and Sr2+ has already been studied in detail, but the addition of antibacterial cations (Ag+ and Cu2+) on the Mg–Sr β-TCP co-doped composition remains unexplored. Thus, two co-doped β-TCP compositions were realized by aqueous precipitation technique without any secondary phase and compared with undoped β-TCP: Mg–Sr (2.0–2.0 mol%) and Mg–Sr–Ag–Cu (2.0–2.0–0.1–0.1 mol%). Differential thermal analysis and dilatometry analyses showed a slight decrease of the β-TCP → α-TCP phase transition temperature for the Mg–Sr–Ag–Cu (2.0–2.0–0.1–0.1% mol) composition as compared to the Mg–Sr (2.0–2.0 mol%). However, both exhibited much higher transition temperatures than undoped β-TCP. The addition of Ag+ and Cu2+ slightly reduces the grain size after sintering compared to the Mg–Sr (2.0–2.0 mol%) and the undoped compositions. The co-doped compositions also exhibited improved mechanical properties, specifically a higher Vickers hardness and elastic modulus. Finally, cell proliferation assays showed that the presence of dopants, even Ag+ and Cu2+, does not affect the survival and proliferation of cells. Thus, the use of Mg2+, Sr2+, Ag+, and Cu2+ co-doped β-TCP could be very promising for biomedical applications due to the improvements of these dopants on the thermal stability and mechanical and biological properties.
Disciplines :
Chemistry
Author, co-author :
Somers, Nicolas ; Université de Liège - ULiège > Complex and Entangled Systems from Atoms to Materials (CESAM) ; Univ. Polytechnique Hauts-de-France—CERAMATHS-DMP, Valenciennes, France
Jean, Florian; Univ. Polytechnique Hauts-de-France—CERAMATHS-DMP, Valenciennes, France
Lasgorceix, Marie; Univ. Polytechnique Hauts-de-France—CERAMATHS-DMP, Valenciennes, France
Urruth, Giovanni; CIRIMAT, Université de Toulouse, CNRS, Toulouse, France
The authors are grateful to the “DOC 3D Printing” project for financial support. This project has received funding from the European Union's Horizon 2020 research and innovation program under the Marie Skłodowska-Curie grant agreement no. 764935. The authors would like to congratulate the Young Ceramists Network committee for their work to improve the networking among young ceramist researchers. The authors are also grateful to the ECERS administrative officers for their impressive work on organizing online conferences.66The authors are grateful to the “DOC 3D Printing” project for financial support. This project has received funding from the European Union's Horizon 2020 research and innovation program under the Marie Skłodowska‐Curie grant agreement no. 764935.
Davies JE. Bone bonding at natural and biomaterial surfaces. Biomaterials. 2007;28:5058–67. https://doi.org/10.1016/j.biomaterials.2007.07.049
Bose S, Vahabzadeh S, Bandyopadhyay A. Bone tissue engineering using 3D printing. Mater Today. 2013;16:496–504. https://doi.org/10.1016/j.mattod.2013.11.017
Chamary S, Grenho L, Helena M, Bouchart F, Jorge F, Christophe J-C. Influence of a macroporous β-TCP structure on human mesenchymal stem cell proliferation and differentiation in vitro. Open Ceram. 2021;7:100141. https://doi.org/10.1016/j.oceram.2021.100141
Chamary S, Hautcoeur D, Hornez J-C, Leriche A, Cambier F. Bio-inspired hydroxyapatite dual core-shell structure for bone substitutes. J Eur Ceram Soc. 2017;37:5321–7. https://doi.org/10.1016/j.jeurceramsoc.2017.05.043
Baldwin P, Li DJ, Auston DA, Mir HS, Yoon RS, Koval KJ. Autograft, allograft, and bone graft substitutes: clinical evidence and indications for use in the setting of orthopaedic trauma surgery. J Orthop Trauma. 2019;33:203–13. https://doi.org/10.1097/BOT.0000000000001420
Lin K, Sheikh R, Romanazzo S, Roohani I. 3D printing of bioceramic scaffolds-barriers to the clinical translation: from promise to reality, and future perspectives. Materials (Basel). 2019;12:2660. https://doi.org/10.3390/ma12172660
Habraken W, Habibovic P, Epple M, Bohner M. Calcium phosphates in biomedical applications: materials for the future? Mater Today. 2016;19:69–87. https://doi.org/10.1016/j.mattod.2015.10.008
Sohn HS, Oh JK. Review of bone graft and bone substitutes with an emphasis on fracture surgeries. Biomater Res. 2019;23:4–10. https://doi.org/10.1186/s40824-019-0157-y
Bohner M, Le Gars Santoni B, Döbelin N. β-tricalcium phosphate for bone substitution: synthesis and properties. Acta Biomater. 2020;113:23–41. https://doi.org/10.1016/j.actbio.2020.06.022
Bohner M. Resorbable biomaterials as bone graft substitutes. Mater Today. 2010;13:24–30.
Champion E. Sintering of calcium phosphate bioceramics. Acta Biomater. 2013;9:5855–75
Banerjee SS, Bandyopadhyay A, Bose S. Biphasic resorbable calcium phosphate ceramic for bone implants and local alendronate delivery. Adv Eng Mater. 2010;12:148–55. https://doi.org/10.1002/adem.200980072
Lu H, Zhou Y, Ma Y, Xiao L, Ji W, Zhang Y. Current application of beta-tricalcium phosphate in bone repair and its mechanism to regulate osteogenesis. Front Mater. 2021;8:1–16. https://doi.org/10.3389/fmats.2021.698915
Boilet L, Descamps M, Rguiti E, Tricoteaux A, Lu J, Petit F, et al. Processing and properties of transparent hydroxyapatite and β tricalcium phosphate obtained by HIP process. Ceram Int. 2013;39:283–8. https://doi.org/10.1016/j.ceramint.2012.06.023
Descamps M, Hornez JC, Leriche A. Effects of powder stoichiometry on the sintering of β-tricalcium phosphate. J Eur Ceram Soc. 2007;27:2401–6. https://doi.org/10.1016/j.jeurceramsoc.2006.09.005
Hudon P, Jung I-H. Critical evaluation and thermodynamic optimization of the CaO-P2O5 system. Metall Mater Trans B: Process Metall Mater Process Sci. 2015;46:494–522. https://doi.org/10.1007/s11663-014-0193-x
Renaudin G, Jallot E, Nedelec JM. Effect of strontium substitution on the composition and microstructure of sol-gel derived calcium phosphates. J Sol-Gel Sci Technol. 2009;51:287–94. https://doi.org/10.1007/s10971-008-1854-5
Banerjee SS, Tarafder S, Davies NM, Bandyopadhyay A, Bose S. Understanding the influence of MgO and SrO binary doping on the mechanical and biological properties of β-TCP ceramics. Acta Biomater. 2010;6:4167–74. https://doi.org/10.1016/j.actbio.2010.05.012
Tarafder S, Dernell WS, Bandyopadhyay A, Bose S. SrO- and MgO-doped microwave sintered 3D printed tricalcium phosphate scaffolds: mechanical properties and in vivo osteogenesis in a rabbit model. J Biomed Mater Res Part B: Appl Biomater. 2015;103:679–90. https://doi.org/10.1002/jbm.b.33239
Gomes S, Vichery C, Descamps S, Martinez H, Kaur A, Jacobs A, et al. Cu-doping of calcium phosphate bioceramics: from mechanism to the control of cytotoxicity. Acta Biomater. 2018;65:462–74. https://doi.org/10.1016/j.actbio.2017.10.028
Enderle R, Götz-Neunhoeffer F, Göbbels M, Müller FA, Greil P. Influence of magnesium doping on the phase transformation temperature of β-TCP ceramics examined by Rietveld refinement. Biomaterials. 2005;26:3379–84. https://doi.org/10.1016/j.biomaterials.2004.09.017
Frasnelli M, Sglavo VM. Effect of Mg2+ doping on beta-alpha phase transition in tricalcium phosphate (TCP) bioceramics. Acta Biomater. 2016;33:283–9. https://doi.org/10.1016/j.actbio.2016.01.015
Somers N, Jean F, Lasgorceix M, Curto H, Urruth G, Thuault A, et al. Influence of dopants on thermal stability and densification of β-tricalcium phosphate powders. Open Ceram. 2021;7:100168. https://doi.org/10.1016/j.oceram.2021.100168
Tarafder S, Balla VK, Davies NM, Bandyopadhyay A, Bose S. Microwave-sintered 3D printed tricalcium phosphate scaffolds for bone tissue engineering. J Tissue Eng Regen Med. 2012;13:512–20. https://doi.org/10.1002/term.555
Thesis Obadia L. Synthèse et caractérisation des phosphates de calcium d'intérêt biologique: structure et propriétés de phosphates tricalciques β dopés au sodium, formation d'apatites non stoechiométriques par hydrolyse de phosphate dicalcique dihydraté [Université de Nantes]. 2004. Retrieved from https://archive.bu.univ-nantes.fr/pollux/show/show?id=1bb1bd7b-4e60-4f01-89aa-470d0ac37d9f
Cacciotti I, Bianco A. High thermally stable Mg-substituted tricalcium phosphate via precipitation. Ceram Int. 2011;37:127–37.
Bracci B, Torricelli P, Panzavolta S, Boanini E, Giardino R, Bigi A. Effect of Mg2+, Sr2+, and Mn2+ on the chemico-physical and in vitro biological properties of calcium phosphate biomimetic coatings. J Inorg Biochem. 2009;103:1666–74
García-Páez IH, Carrodeguas RG, De Aza AH, Baudín C, Pena P. Effect of Mg and Si co-substitution on microstructure and strength of tricalcium phosphate ceramics. J Mech Behav Biomed Mater. 2014;30:1–15
Veljovic D, Radovanovic Z, Dindune A, Palcevskis E, Krumina A, Petrovic R, et al. The influence of Sr and Mn incorporated ions on the properties of microwave single- and two-step sintered biphasic HAP/TCP bioceramics. J Mater Sci. 2014;49:6793–802. https://doi.org/10.1007/s10853-014-8380-3
Bellucci D, Sola A, Cacciotti I, Bartoli C, Gazzarri M, Bianco A, et al. Mg- and /or Sr-doped tricalcium phosphate/bioactive glass composites: synthesis, microstructure and biological responsiveness. Mater Sci Eng C. 2014;42:312–24. https://doi.org/10.1016/j.msec.2014.05.047
Yamasaki N, Hirao M, Nanno K, Sugiyasu K, Tamai N, Yoshikawa H, et al. A comparative assessment of synthetic ceramic bone substitutes with different composition and microstructure in rabbit femoral condyle model. J Biomed Mater Res Part B: Appl Biomater. 2009;91:788–98. https://doi.org/10.1002/jbm.b.31457
Zhang J, Wu H, He F, Wu T, Zhou L, Ye J. Concentration-dependent osteogenic and angiogenic biological performances of calcium phosphate cement modified with copper ions. Mater Sci Eng C. 2019;99:1199–212. https://doi.org/10.1016/j.msec.2019.02.042
Fadeeva IV, Gafurov MR, Kiiaeva IA, Orlinskii SB, Kuznetsova LM, Filippov YY, et al. Tricalcium phosphate ceramics doped with silver, copper, zinc, and iron (III) ions in concentrations of less than 0.5 wt.% for bone tissue regeneration. Bionanoscience. 2017;7:434–8. https://doi.org/10.1007/s12668-016-0386-7
Li G, Zhang N, Zhao S, Zhang K, Li X, Jing A, et al. Fe-doped brushite bone cements with antibacterial property. Mater Lett. 2018;215:27–30. https://doi.org/10.1016/j.matlet.2017.12.054
Laskus A, Kolmas J. Ionic substitutions in non-apatitic calcium phosphates. Int J Mol Sci. 2017;18:1–22. https://doi.org/10.3390/ijms18122542
Gokcekaya O, Ueda K, Narushima T, Ergun C. Synthesis and characterization of Ag-containing calcium phosphates with various Ca/P ratios. Mater Sci Eng C. 2015;53:111–9.
Liu S, Fan C, Jin F, Zhao L, Dai K, Lu J. Preparation and antibacterial activities of porous silver-doped β-tricalcium phosphate bioceramics. Int J Appl Ceram Technol. 2015;12:294–9.
Fadeeva IV, Lazoryak BI, Davidova GA, Murzakhanov FF, Gabbasov BF, Petrakova NV, et al. Antibacterial and cell-friendly copper-substituted tricalcium phosphate ceramics for biomedical implant applications. Mater Sci Eng C. 2021;129:112410. https://doi.org/10.1016/j.msec.2021.112410
Cummings HV. Physical and biological properties of cobalt- and copper-doped calcium phosphates as bone substitute materials (Issue NASA/TM–2018–220015 Physical). Moffett Field, California. 2018. Retrieved from https://rotorcraft.arc.nasa.gov/Publications/files/Cummings_TM-2018-220015.pdf
Vandecandelaere N. Élaboration et caractérisation de biomatériaux osseux innovants à base d'apatites phospho-calciques dopées. Toulouse: Université de Toulouse; 2012.
Bazin T, Magnaudeix A, Mayet R, Carles P, Julien I, Demourgues A, et al. Sintering and biocompatibility of copper-doped hydroxyapatite bioceramics. Ceram Int. 2021;47:13644–54. https://doi.org/10.1016/j.ceramint.2021.01.225
Doebelin N, Kleeberg R. Profex: a graphical user interface for the Rietveld refinement program BGMN. J Appl Crystallogr. 2015;48:1573–80. https://doi.org/10.1107/S1600576715014685
Abercrombie M. Estimation of nuclear population from microtome sections. Anat Rec. 1946;94:239–47. https://doi.org/10.1002/ar.1090940210
Tricoteaux A, Rguiti E, Chicot D, Boilet L, Descamps M, Leriche A, et al. Influence of porosity on the mechanical properties of microporous β-TCP bioceramics by usual and instrumented Vickers microindentation. J Eur Ceram Soc. 2011;31:1361–9. https://doi.org/10.1016/j.jeurceramsoc.2011.02.005
Hay J, Agee P, Herbert E. Continuous stiffness measurement during instrumented indentation testing. Exp Tech. 2010;34:86–94. https://doi.org/10.1111/j.1747-1567.2010.00618.x
Matsumoto N, Sato K, Yoshida K, Hashimoto K, Toda Y. Preparation and characterization of β-tricalcium phosphate co-doped with monovalent and divalent antibacterial metal ions. Acta Biomater. 2009;5:3157–64. https://doi.org/10.1016/j.actbio.2009.04.010
Kannan S, Goetz-Neunhoeffer F, Neubauer J, Pina S, Torres PMC, Ferreira JMF. Synthesis and structural characterization of strontium- and magnesium-co-substituted β-tricalcium phosphate. Acta Biomater. 2010;6:571–6. https://doi.org/10.1016/j.actbio.2009.08.009
Destainville A, Champion E, Laborde E. Synthesis, characterization and thermal behavior of apatitic tricalcium phosphate. Mater Chem Phys. 2003;80:269–77.
Cacciotti I, Bianco A, Lombardi M, Montanaro L. Mg-substituted hydroxyapatite nanopowders: synthesis, thermal stability and sintering behaviour. J Eur Ceram Soc. 2009;29:2969–78. https://doi.org/10.1016/j.jeurceramsoc.2009.04.038
Destainville A, Rolo A, Champion E, Bernache-Assollant D. Synthesis and characterization of beta tricalcium phosphate. Key Eng Mater. 2003; 240–242:489–92. https://doi.org/10.4028/www.scientific.net/KEM.240-242.489
Douard N, Detsch R, Chotard-ghodsnia R, Damia C, Deisinger U, Champion E. Processing, physico-chemical characterisation and in vitro evaluation of silicon containing β-tricalcium phosphate ceramics. Mater Sci Eng C. 2011;31:531–9. https://doi.org/10.1016/j.msec.2010.11.008
Gallo M, Le Gars Santoni B, Douillard T, Zhang F, Gremillard L, Dolder S, et al. Effect of grain orientation and magnesium doping on β-tricalcium phosphate resorption behavior. Acta Biomater. 2019;89:391–402. https://doi.org/10.1016/j.actbio.2019.02.045
Ryu HS, Hong KS, Lee JK, Kim DJ, Lee JH, Chang BS, et al. Magnesia-doped HA/β-TCP ceramics and evaluation of their biocompatibility. Biomaterials. 2004;25:393–401. https://doi.org/10.1016/S0142-9612(03)00538-6
Ryu HS, Youn HJ, Hong KS, Chang BS, Lee CK, Chung SS. An improvement in sintering property of β-tricalcium phosphate by addition of calcium pyrophosphate. Biomaterials. 2002;23:909–14. https://doi.org/10.1016/s0142-9612(01)00201-0
Sheinerman AG, Castro RHR, Yu M. A model for direct and inverse Hall-Petch relation for nanocrystalline ceramics. Mater Lett. 2020;260:126886. https://doi.org/10.1016/j.matlet.2019.126886
Meyers MA, Mishra A, Benson DJ. Mechanical properties of nanocrystalline materials. Prog Mater Sci. 2006;51:427–556. https://doi.org/10.1016/j.pmatsci.2005.08.003
Wollmershauser JA, Feigelson BN, Gorzkowski EP, Ellis CT, Goswami R, Qadri SB, et al. An extended hardness limit in bulk nanoceramics. Acta Mater. 2014;69:9–16. https://doi.org/10.1016/j.actamat.2014.01.030
Hall EO. The deformation and ageing of mild steel: III discussion of results. Proc Phys Soc Sect B. 1951;64:747.
Veljovic D, Miodrag C, Kojic V, Bogdanovic G, Kojic Z, Banjac A, et al. The effect of grain size on the biocompatibility, cell – materials interface, and mechanical properties of microwave-sintered bioceramics. J Biomed Mater Res A. 2012;100(11):3059–70. https://doi.org/10.1002/jbm.a.34225
Dasgupta S, Tarafder S, Bandyopadhyay A, Bose S. Effect of grain size on mechanical, surface and biological properties of microwave sintered hydroxyapatite. Mater Sci Eng C. 2013;33:2846–54.
Kim TN, Balakrishnan A, Lee BC, Kim WS, Dvorankova B, Smetana K, et al. In vitro fibroblast response to ultra fine grained titanium produced by a severe plastic deformation process. J Mater Sci: Mater Med. 2008;19(2):553–7. https://doi.org/10.1007/s10856-007-3204-5
Catledge SA, Fries MD, Vohra YK, Lace WR, Lemons JE, Woodard S, et al. Nanostructured ceramics for biomedical implants. J Nanosci Nanotechnol. 2002;2:293–312. https://doi.org/10.1166/jnn.2002.116
Bose S, Dasgupta S, Tarafder S, Bandyopadhyay A. Microwave-processed nanocrystalline hydroxyapatite: simultaneous enhancement of mechanical and biological properties. Acta Biomater. 2010;6:3782–90. https://doi.org/10.1016/j.actbio.2010.03.016
Koruza J, Klein A. Electroceramics XVII – The 2020 virtual conference experience at TU Darmstadt. Open Ceram. 2022;6:1–5. https://doi.org/10.1016/j.oceram.2021.100114
