ISSN 00125008, Doklady Chemistry, 2016, Vol. 467, Part 1, pp. 100–104. © Pleiades Publishing, Ltd., 2016. Original Russian Text © M.A. Goldberg, V.V. Smirnov, O.S. Antonova, S.V. Smirnov, L.I. Shvorneva, S.V. Kutsev, S.M. Barinov, 2016, published in Doklady Akademii Nauk, 2016, Vol. 467, No. 2, pp. 180–184.
CHEMICAL TECHNOLOGY
MagnesiumSubstituted Calcium Phosphate Cements with (Ca + Mg)/P = 2 M. A. Goldberg, V. V. Smirnov, O. S. Antonova, S. V. Smirnov, L. I. Shvorneva, S. V. Kutsev, and Corresponding Member of the RAS S. M. Barinov Received October 30, 2015
Abstract—The introduction of magnesium ions into bone calcium phosphate cements (CPCs) increases the strength and biodegradation rate of the materials. Cement powders with the (Ca + Mg)/P ratio of 2 and the degree of magnesium substitution for calcium of 0, 10, 20, and 40 wt % were used in the study. Sodium phos phatebased solutions were used as the cement fluids. Depending on the magnesium content, CPCs based on magnesiumsubstituted apatite and whitlockite phases were obtained. The phase composition, setting time, strength, and microstructure of the cements were determined. An increase in the acidity of the cement liquid was found to give cements with a greater content of amorphous phase and more homogeneous structure, resulting in higher strength. DOI: 10.1134/S0012500816030046
Bone calcium phosphate cements (CPC) are used in orthopedics and dentistry to fill cavities, insert implants, and connect tissue fragments. The introduc tion of magnesium ions into CPCs increases the strength and biodegradation rate of the materials [1, 2]. There are CPCs in which magnesium compounds are introduced via the liquid phase on mixing with the cement powder [3, 4]. A new approach implies devel opment of cement powders with a specified content of magnesium ions. One can expect that upon mixing with the cement liquid, these cement powders would form saturated solutions that would transform into a strong cement matrix upon setting and hardening. This method makes it possible to pass to onecompo nent powder cements and to use cement liquids with nearly neutral pH. This would markedly simplify the technology of cement materials for medicine, in par ticular, chemical burns associated with the use of known magnesiumcontaining acidic cement liquids could be avoided. Magnesiumcontaining CPCs known from the literature have compositions of the powder phase resembling hydroxyapatite, tricalcium phosphate, or trimagnesium phosphate with the ratio (Ca + Mg)/P = 1.5–1.7 and give dicalcium phosphate dihydratebased cements [2, 5]. Bone cements of the calcium phosphate–magnesium phosphate systems may be developed by using materials with a high cation to anion ratio, (Ca + Mg)/P = 2, which promotes the formation of cements based on magnesiumsubsti
Baikov Institute of Metallurgy, Russian Academy of Sciences, Leninskii pr. 49, Moscow, 117334 Russia email:
[email protected]
tuted apatite phase or tricalcium phosphate phase pos sessing higher strength than dicalcium phosphate dihydratebased cements. This was the subject of the present research. EXPERIMENTAL Calcium phosphate–magnesium phosphate pow ders with the ratio (Ca + Mg)/P = 2 and the degree of magnesium substitution for calcium of 0, 10, 20, and 40 wt % were used as the powder phase. The synthesis was carried out as described in [6]. The initial com pounds for the preparation of cement powders included Mg(NO3)2 · 6H2O, (NH4)2HPO4, and Ca(NO3)2 ⋅ 4H2O (all analytical grade chemicals). The powders were heattreated at 1500°C in air and milled in an MP 4/1 planetary ball mill with corundum mill ing balls (LLC TechnoCentr, Russia) for 30 min at 33.3 g with diethyl ketone as the milling medium. The phase composition of the powder phase is presented in Fig. 1. The cement liquids used were concentrated solutions based on sodium phosphates—Na2HPO4 (liquid 1, pH 5.8 ± 0.1) and NaH2PO4 (liquid 2, pH 3.6 ± 0.1). The samples for investigations were prepared by mixing a powder and a liquid in 1 : 1 mass ratio. The resulting cement solutions were placed after mixing into Teflon molds with 5 mm diameter and 10 mm height. The setting time was determined by immersing a steel needle with a diameter of 1 mm into the sample being set until the needle could no longer penetrate by more than 1 mm. [7]. After hardening for 3 days, the cements were studied by powder Xray diffraction on
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Fig. 1. Xray diffraction patterns of the cement powders; (*) apatite phase, (c) tetracalcium phosphate, (×) betatricalcium phos phate, (^) whitlockite phase Ca3Mg3(PO4)4, (v) whitlockite phase Са7Mg2(PO4)6.
an XRD6000 diffractometer (Shimadzu, Japan, CuKα radiation) using automated data collection and processing system. The phase composition was identi fied according to the JCPDS (Joint Committee on Powder Diffraction Standards) database. The com pressive strength of the cement samples was measured on an Instron 5581 tensile machine (TTS, UK), and the final statistical calculations were carried out for 5 samples. The microstructure of materials was stud ied by scanning electronic microscopy on a Vega II microscope (Tescan, Czechia, secondary ion mode, 15 kV voltage). RESULTS AND DISCUSSION The setting time of cements with 0, 10, and 20 wt % magnesium substitution for calcium decreases from 8–10 to 5–6 min with increasing magnesium content. As the acidity of the cement liquid increases (on going from liquid 1 to liquid 2), the setting time decreases insignificantly (from 8–9 to 4–5 min.). For materials with 40 wt % magnesium substitution for calcium, the setting time was 5–6 min for liquid 1 and 4–5 min for liquid 2. As can be seen from Fig. 1, cement powders of magnesiumfree materials consist of tetracalcium phosphate and the apatite phase. The materials with 10 and 20 wt % magnesium substitution for calcium DOKLADY CHEMISTRY
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consist of the apatite phase, magnesiumsubstituted whitlockite Ca3Mg3(PO4)4, tetracalcium phosphate, betatricalcium phosphate, and magnesium oxide. In the material with 40 wt % substitution, the major phases are magnesium oxide and magnesiumsubsti tuted whitlockite Ca3Mg3(PO4)4 and Са7Mg2(PO4)6. According to powder diffraction data, upon mixing with the liquid, cement powders with degrees of mag nesium substitution for calcium of 0, 10, and 20 wt % form cement materials with predominating amor phous phase (up to 80 wt %). The crystalline part mainly consists of the apatite phase and a minor amount of tetracalcium phosphate. Upon introduc tion of magnesium ions, the magnesiumsubstituted whitlockite phase Ca3Mg3(PO4)4 and magnesium oxide are also formed. The magnesium oxide content reaches 5 wt % following increase in the magnesium content in the material (Fig. 2). The magnesiumfree powder (0 wt %) and the cement liquid react to decrease the amount of tetracalcium phosphate and increase the intensity of apatite peaks. The formation of cements with 10 and 20 wt % magnesium substitu tion involves the reaction of tetracalcium phosphate, magnesiumsubstituted whitlockite phase, and mag nesium oxide with the cement liquid, which results in formation of amorphous and apatite phases with a low degree of crystallization. At higher magnesium con tents, the degree of crystallization of the cements
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0 wt % Mg 60
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Fig. 2. Xray diffraction patterns of the cement obtained using (a) liquid 1 and (b) liquid 2; (*) apatite phase (c) tetracalcium phos phate, (^) whitlockite phase Ca3Mg3(PO4)4, (䉫) MgO.
increases. It was found that increase in the acidity of the cement liquid used induces a decrease in the degree of crystallization of cements, an increase in the amount of the amorphous phase, and a considerable reduction of the amount of tetracalcium phosphate in the crystalline phase accompanied by the correspond ing growth of the amount of the apatite phase. Powders with 40 wt % magnesium substitution formed cement materials based on the amorphous phase and crystalline magnesium oxide and only one magnesiumsubstituted compound – the whitlockite phase Са3Mg3(PO4)4 (Fig. 3) with a low degree of
crystallization. This is due to the fact that magnesium present in excess is incorporated in the whitlockite phase Са7Mg2(PO4)6 as magnesium oxide. If liquid 2 was used, the degree of crystallization of the whitlock ite phase was lower. In the next stage of the study, we considered the compressive strength of the samples and found that the application of liquid 2 substantially increased the strength of the cements (table). In the series of apatite cement samples (0, 10, and 20 wt % Mg), the strength slightly increased with increasing magnesium content. The highest strength (36–40 MPa) was found for DOKLADY CHEMISTRY
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Fig. 3. Xray diffraction pattern of the cements obtained from powders with 40 wt% Mg2+ substitution for Ca2+; (^) whitlockite phase Ca3Mg3(PO4)4, (䉫)MgO.
the series of cements obtained from materials with 40 wt % magnesium substitution and liquid 2. Then, we studied the microstructure of the cement materials and found that the apatite cements devoid of magnesium are composed of nondense 5–10 µm agglomerates connected by the cementing amorphous phase with up to 20 µm grains (Fig. 4). On going from liquid 1 to liquid 2, no substantial change in the micro structure takes place. The introduction of magnesium into the materials does not change the type of the microstructure but leads to a decrease in the size of particles forming agglomerates down to 3–5 µm. The microstructure of the cements with 40 wt % substitu tion of Mg2+ for Ca2+ changes considerably on going from liquid 1 to liquid 2. In the case of materials obtained using liquid 1, the microstructure becomes inhomogeneous and nondense, consisting of 2 to
10 µm particles. The use of liquid 2 promotes a consid erable increase in the cement density with grain size decreasing to 2–5 µm. The structure becomes more homogeneous and the amorphous phase predomi nates. This microstructure leads to enhancement of the mechanical properties of cement materials. Thus, we obtained new CPCs in the calcium phos phate–magnesium phosphate system with the ratio (Ca + Mg)/P = 2 and a degree of substitution of Mg2+ for Ca2+ of up to 40 wt%. An increase in the acidity of the cement liquid results in the formation of cements with a higher content of the amorphous phase and with higher mechanical properties. We also demon strated that, depending on the magnesium content in the powder phase, CPCs based on either apatite or whitlockite magnesiumsubstituted phase with a strength of up to 40 MPa are formed. The cements we
Strength of cements Degree of magnesium substitution for calcium, wt % Type of cement liquid phase
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5.5 ± 0.7 12.3 ± 0.5
0.9 ± 0.5 38.2 ± 1.5
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Fig. 4. Microstructure of the cement materials with 40 wt% Mg2+ substitution for Ca2+ obtained using (a) liquid 1 and (b) liquid 2.
developed may find use in medicine for bone defect treatment. ACKNOWLEDGMENTS This work was supported by the Russian Founda tion for Basic Research, project no. 14–08–31204 mola. REFERENCES
2. Lilley, K.J., Gbureck, U., Knowles, J.C., et al., J. Mater. Sci. Mater. Med., 2005, vol. 16, no. 5, pp. 455–460. 3. Rau, J.V., Generosi, A., Smirnov, V.V., et al., Acta Bio mater., 2008, vol. 4, no. 4, pp. 1089–1094. 4. Smirnov, V.V., Barinov, S.M., Komlev, V.S., and Gold berg, M.A., Materialovedenie, 2012, vol. 6, pp. 50–53. 5. Klammert, U., Reuther, T., Blank, M., et al., Acta Bio mater., 2010, vol. 6, no. 4, pp. 1529–1535. 6. Goldberg, M.A., Smirnov, V.V., Kasimova, M.R., et al., Dokl. Chem., 2015, vol. 461, no. 1, pp. 81–85. 7. Wu, F., Wei, J., Guo, H., et al., Acta Biomater., 2008, vol. 4, no. 6, pp. 1873–1884.
1. Pina, S., Olhero, S.M., Gheduzzi, S., et al., Acta Biom ater., 2009, vol. 5, no. 4, pp. 1233–1240.
Translated by Z. Svitanko
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