J O U R N A L O F M A T E R I A L S S C I E N C E L E T T E R S 2 0, 2 0 0 1, 1225 – 1227
Preparation of biphasic calcium phosphate doped with magnesium fluoride for osteoporotic applications I . M A N J U B A L A ∗, T . S . S A M P A T H K U M A R ‡ Materials Science Centre, Department of Nuclear Physics, University of Madras, Guindy Campus, Chennai 600 025, India E-mail:
[email protected]
Calcium hydroxyapatite Ca10 (PO4 )6 (OH)2 (HA) and tricalcium phosphate Ca3 (PO4 )2 (TCP) are the commonly used calcium phosphate ceramics for bone replacement due to their biocompatibility [1, 2]. However, they differ in the rate of bioresorption. HA resorbs very slowly compared to TCP and the variation in their Ca/P ratio is known to lead to difference in their biodegradability [3]. Some investigations reported that the rate of biodegradation of β-TCP was too fast for optimum bonding to bone [4]. Recently many studies claimed that the biphasic calcium phosphate (BCP) ceramics consisting of mixture of TCP and HA in various ratios have demonstrated more efficiency in the repair of bone defects than pure HA and pure TCP alone [4–6]. The bioactivity and the resorbability of the BCP ceramics are controlled by the HA/TCP ratio. Even the crystalline mineral phase composition of sintered cancellous bone was found to be similar to BCP i.e. mainly consisting of about 93 wt% of hydroxyapatite and about 7 wt% of tricalcium phosphate [7]. The main ionic constituents of the inorganic compo2− − sition of bone are Ca2+ , PO3− 4 , OH , CO3 and citrate + ions and the minor elements are Na , Mg2+ , Cl− and F− ions. These minor ions are incorporated in either the HA or TCP crystal structure to replace the position of calcium, phosphorus or hydroxyl ions. The stability and solubility of these calcium phosphates depends on the chemistry and structure i.e. impurities substituted in the lattice. The F− and Mg2+ ions substitute in the HA and TCP lattice respectively and influence the stability and solubility properties of HA and TCP phases [8]. Fluoride and magnesium therapies are well known for treatment of osteoporosis. Hence in the present study an attempt is made to incorporate both Mg2+ and F− ions in calcium phosphates. During the in-situ preparation of BCP using microwave irradiation magnesium fluoride solution is added. The microwave synthesis of ceramics offers the advantages of heating the entire volume in very short time leading to fine crystallites which also influences the resorption rate of the BCP ceramics. Since the absorption of microwave energy varies with the composition and structure of different phases, selective heating is also possible. The preparation of biphasic calcium phosphates using microwaves is described elsewhere in detail [9].
BCP ceramic consisting of 60% HA and 40% TCP composition with Ca/P = 1.58 was prepared using Ca(OH)2 and (NH4 )2 HPO4 for calcium and phosphate precursors. The precursor solution was mixed and irradiated with microwaves of frequency 2.45 GHz in a domestic microwave oven. The doped BCP ceramics were prepared by adding magnesium fluoride (2–15 mol%) during the preparation of BCP. All the samples prepared were used in powder form and sintered at 900 ◦ C for 12 h in air and then used for further characterization. The powders were examined with an X-ray diffractometer using monochromatic Cu Kα radiation in Guinier geometry. Infrared spectra were obtained for the powdered samples by KBr pellet method and the in-vitro stability analysis of the samples were carried out in phosphate buffered solution of pH 7.2 at 37 ◦ C. The observed X-ray diffractograms (XRD) of the sintered doped and undoped BCP samples are shown in Fig. 1. The patterns of the pure HA heated under identical conditions is shown as reference material (Fig. 1a). The diffractogram of the dopant free BCP confirms the presence of both HA (JCPDS 9-432 file) and β-TCP phase (JCPDS 9-169 file) but without any other calcium phosphates like tetracalcium phosphate or calcium oxide. The intensity of the main peaks of β-TCP phase decreases for 2 mol% MgF2 doped BCP. The intensity of the main peaks of β-TCP increases as the concentration of MgF2 increases from 5 to 15 mol%. Since there is no characteristic whitlockite peak at 28◦ , only a partial substitution of Mg2+ occurs in the TCP. The shift in the main peaks of the TCP also suggests the substitution of Mg2+ ions in Ca2+ site of TCP. The changes observed in the d-spacing of the (0210/217) peak of TCP and (211) peak of HA are listed in Table I. The Mg2+ ions replace the Ca2+ ion position in the TCP lattice to form either Mg3 (PO4 )2 or Ca3−x Mgx (PO4 )2 and the X-ray diffraction pattern indicates that there is no Mg3 (PO4 )2 peaks and only the substitution of doping of Mg2+ ions in the Ca2+ site by the peak shift. The effect of F− ions seems to be predominant than the Mg2+ ions for 2 mol% MgF2 addition that results in the formation of more HA than stabilizing the TCP phase. In presence of both Mg2+ and the F− ions, the stabilizing agents of the TCP and HA respectively, the
∗ Author to whom all correspondence should be addressed. ‡ Present
Address: Department of Metallurgical Engineering and RSIC, Indian Institute of Technology-Madras, Chennai 600 036, India.
C 2001 Kluwer Academic Publishers 0261–8028
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Figure 2 FT-IR spectra of a) 2 mol% and b) 10 mol% of MgF2 doped BCP.
Figure 1 X-ray diffraction patterns of (a) pure HA, (b) undoped BCP, (c) 2 mol%, (d) 5 mol%, (e) 10 mol% and (f ) 15 mol% of MgF2 doped BCP. () TCP peaks. The indexed peaks in pattern (a) are HA peaks and in pattern (f ) are β-TCP peaks.
effect of Mg2+ ions seems to be predominant in the 5–15 mol% doped samples with the evolution of more TCP phase whereas in the 2 mol% doped sample the HA is stabilized by the F− ions. The quantitative measurement on the evolution of β-TCP phase in the BCP phase were calculated using the integrated intensities of the (0210) peak of TCP phase and (211) peak of HA phase using the formula ITCP /(ITCP + IHA ) as reported earlier [9]. However, if we use the other precursor of Mg ions such as MgCl2 , Mg(OH)2 , it would either form other stable compounds such as chlorinated HA or remain difficult to remove as MgO formed during the heat treatment. Hence MgF2 has been chosen as a suitable compound for doping the BCP ceramics. The FT-IR spectra of 2 and 10 mol% MgF2 doped BCP samples are shown in Fig. 2 to observe the changes in the calcium phosphate phases due to doping. The characteristic bands corresponding to PO3− 4 in the range 560–600, 1030–1090 cm−1 are observed. The 1046 and 983 cm−1 bands are assigned to the stretching
−1 vibrations of the PO3− 4 ions and the 605 and 557 cm bands are assigned to the deformation vibrations of the PO3− 4 ions. The band due to the stretching vibrations of OH− ions at 3571 cm−1 smears out while the band at 624 cm−1 due to the vibration motion of the OH− disappears as the TCP content increases in the 10% MgF2 doped sample. The in-vitro stability of the undoped and the 5 and 10 mol% MgF2 doped BCP ceramics were evaluated in the phosphate buffered solution at pH 7.2 and the pH variation of the solution are shown in the Fig. 3. All the samples show continuous decrease of pH which may be due to the dissolution of TCP phase. The decrease in the pH was more for the 10% doped sample as expected, due to the presence of less amount of HA phase. Some investigations have reported that the calcium phosphates doped with F− ions and Mg2+ ions
T A B L E I The variation in the d-spacing of the main peak of TCP (217) and HA (211) phase Sample
TCP (217)
TCP BCP 2% MgF2 5% MgF2 10% MgF2 15% MgF2 HA
2.8875 2.8587 2.8587 2.8551 2.8551 2.8550
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HA (211)
2.8097 2.8131 2.8062 2.8024 2.7998 2.8144
Figure 3 In-vitro solubility studies in phosphate buffer of pH 7.2 (a) undoped BCP, (b) 5 mol% and (c) 10 mol% MgF2 doped BCP ceramic.
leads to a decrease of the degradation rate of the material in vivo [10]. Due to the complex formation depending on the buffering conditions, the role of the dopant ion in stabilizing the calcium phosphates may be clearly observed with a suitable physiological solution. In summary, microwave processing of bioceramics seems to be a faster technique to obtain in-situ formation of BCP ceramics. The 2 mol% MgF2 doped BCP ceramic stabilizes HA phase than TCP phase indicating that the F− effect is predominant. For higher content of MgF2 , the Mg2+ ion effect seems to be predominant by stabilizing the TCP and producing more amount of TCP in BCP ceramics. References 1. S . K O T A N I , Y . F U J I T A , T . K I T S U G I , T . N A K A M U R A , T . Y A M A M U R O , C . O H T S U K I and T . K O K U B O , J. Biomed. Mater. Res. 25 (1991) 1303.
2. M . J A R C H O , Clin. Orthop. Rel. Res. 157 (1981) 259. 3. C . P . A . T . K L E I N , A . A . D R E I S S E N , K . D E G R O O T and A . V A N D E N H O O F , J. Biomed. Mater. Res. 17 (1983) 769. 4. M . K O H R I , K . M I K I , D . E . W A I T E , H . N A K A J I M A and T . O K A B E , Biomaterials 14 (1993) 299. 5. P . F R A Y S S I N E T , J . L . T R A I L L E T , N . R O U Q U E T , E . A Z I M U S and A . A U T E F A G E , ibid. 14 (1993) 423. 6. E . B . N E R Y , R . Z . L E G E R O S , L . L . L Y N C H and K . L E E , J. Periodontal 63 (1992) 729. 7. B . D . K A T T H A G E N , “Bone Regeneration with Bone Substitutes” (CRC Press, Boca Raton, FL, 1983). 8. C . R E Y , Biomaterials 11 (1990) 13. 9. I . M A N J U B A L A and T . S . S A M P A T H K U M A R , Materials Chemistry and Physics (communicated). 10. C . P . A . T . K L E I N , K . D E G R O O T , A . A . D R I E S S E N and H . B . M . V A N D E R L U B B E , Biomaterials 7 (1986) 144.
Received 15 August 2000 and accepted 17 April 2001
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