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Chem. Mater. 2004, 16, 2300-2308
Silicon Incorporation in Hydroxylapatite Obtained by Controlled Crystallization D. Arcos,*,† J. Rodrı´guez-Carvajal,† and M. Vallet-Regı´‡ Laboratoire Le´ on Brillouin (CEA-CNRS), Centre d’Etudes de Saclay, F-91191 Gif-sur-Yvette Cedex, France, and Departamento de Quı´mica Inorga´ nica y Bioinorga´ nica, Facultad de Farmacia, Universidad Complutense, 28040 Madrid, Spain Received December 17, 2003. Revised Manuscript Received March 26, 2004
Silicon-containing hydroxylapatites have been prepared by an aqueous precipitation method, partially substituting phosphate with silicate groups. The as-prepared products contain two phases: an amorphous phase and an apatite phase. At this first stage, the phosphate deficiency is not primarily compensated by silicate incorporation, but by carbonates contained in the aqueous media. The silicon plays a very important role at the microstructural level, taking part in increasing the amount of the amorphous phase, as well as leading to smaller crystallite size. After removing the carbonates by treating the samples at 900 °C, the Si seems to get into the apatite structure. This incorporation also leads to structural changes and higher tetrahedral distortion compared to that of pure hydroxylapatite, which can explain the higher reactivity of these compounds previously reported by other authors.
Introduction Synthetic hydroxyapatite (HA) is one of the most important bioceramics used in dentistry and orthopedic surgery.1-4 Its composition, Ca10(PO4)6(OH)2, is very similar to that of the biological apatite that forms the mineral fractions of bone tissue. The structure of HA can be described as a hexagonal unit cell with space group P63/m and lattice parameters a ) 9.432 Å and c ) 6.881 Å, having one formula unit Ca10(PO4)6(OH)2 per unit cell.5 The hydroxyl ions and four Ca ions at Ca(I) sites lie along columns parallel to the c axis. The hydroxyls are sited along the c axis and the O-H bond direction is parallel to it, without straddling the mirror planes at z ) 1/4 and 3/4. The remaining six Ca atoms, positioned at Ca(II) sites, are associated with the two hydroxyl groups in the unit cell, where they form triangles centered on, and perpendicular to, the OH axis and laying on the mirror planes. The phosphate tetrahedral PO4 forms the remaining basic structural unit of HA. The HA biocompatibility is excellent,6-8 however the bioactive behavior can be improved by introducing some substitutions into the structure. Actually, the apatite † Laboratoire Le ´ on Brillouin (CEA-CNRS), Centre d’Etudes de Saclay. ‡ Universidad Complutense. (1) Elliott, J. C. Structure and Chemistry of the Apatites and Other Calcium Orthophosphates; Studies in Inorganic Chemistry, No. 18; Elsevier: Amserdam, 1994. (2) LeGeros, R. Z. Calcium Phosphates in Oral Biology and Medicine; Monographs in Oral Science, No. 15; Karger: Basel, Switzerland, 1991. (3) de Groot, K., Ed. Bioceramics of Calcium Phosphate; CRC Press: Boca Raton, FL, 1983; p 100. (4) Vallet-Regı´, M. J. Chem. Soc. Dalton. Trans. 2001, 2, 97. (5) Kay, M. I.; Young, R. A.; Posner, A. S. Nature 1964, 204, 1050. (6) Hench, L. L. J. Am. Ceram. Soc. 1991, 74, 1487. (7) Oonishi, H.; Hench, L. L.; Wilson, J.; Sugihora, F.; Tsuji, E.; Matsuura, M.; Kin, S.; Yamamoto, T.; Mizokawa, S. J. Biomed. Mater. Res. 2000, 51, 37. (8) Ducheine, P.; Qiu, Q. Biomaterials 1999, 20, 2287.
structure can incorporate a wide variety of ions that can affect both cationic and anionic sublattices. The substitutions can incorporate cations with the same oxidation state as Ca2+, such as Sr2+, Pb2+, Mg2+, etc.,9-12 and anions with the same oxidation state as OH-, such as F- or Cl-.13,14 Ionic substitutions with different oxidation states are also very common,15-17 and have an important role in the chemical, structural, and microstructural properties. For example, in biological apatites CO32-, substitution for PO43- (type B) or OH- (type A) is a likely substitution.18,19 In the case of B-type carbonated apatites, the neutrality uses to be reached by the incorporation of single valence cations (Na+ or K+) in the Ca2+ positions.20,21 The studies carried out by Carlisle22,23 indicated the importance of the silicon on bone formation and calcification. Moreover, it has been observed that the addition of Si during the HA synthesis leads to an improve(9) Bigi, A.; Ripamonti, A.; Bru¨ckner, S.; Gazzano, M.; Roveri, N.; Thomas, S. A Acta Crystallogr. 1989, B45, 247. (10) Bigi, A.; Falini, E.; Foresti, M.; Gazzano, M; Ripamonti A.; Roveri, N. Acta Crystallogr. 1996, B52, 87. (11) Ergun, C; Webster, T. J.; Bizios, R.; Doremus, R. H. J. Biomed. Mater. Res. 2002, 59, 305. (12) Webster, T. J.; Ergun, C.; Doremus, R. H.; Bizios, R. J. Biomed. Mater. Res. 2002, 5, 312. (13) Zapanta LeGeros, R. Arch. Oral Biol. 1974, 20, 63. (14) Mackie, P. E.; Elliott, J. C.; Young, R. A. Acta Crystallogr. 1972, B28, 1840. (15) Elliott, J. C.; Bonel, G.; Trombe, J. C. J. Appl. Crystallogr. 1980, 13, 618. (16) DeBoer, B.G. Acta Crystallogr. 1991, B47, 683. (17) Serret, A.; Caban˜as, M. V.; Vallet-Regı´, M. Chem. Mater. 2000, 12, 3836. (18) Young, R. A.; Mackie, P. E. Mater. Res. Bull 1980, 15, 17. (19) Wilson, R. M.; Elliott, J. C.; Dowker, S. E. P. Am. Miner. 1999, 84, 1406. (20) De Maeyer, E. A. P.; Verbeeck, R. M. H.; Naessens, D. E. Inorg. Chem. 1993, 32, 5709. (21) Verbeeck, R. M. H.; De Maeyer, E. A. P.; Driessens, F. C. M. Inorg. Chem. 1995, 34, 2084. (22) Carlisle, E. M. Science 1970, 167, 179. (23) Carlisle, E. M. Calc. Tissue Int. 1981, 33, 27.
10.1021/cm035337p CCC: $27.50 © 2004 American Chemical Society Published on Web 05/07/2004
Synthesis of Silicon-Containing Hydroxylapatites
ment of the bioactive behavior.24,25 This means that the implant is able to join chemically to the bone through a strong “bioactive bond”. In this way, the osteointegration and the good performance of the implant are ensured. Several authors have worked on this subject, assuming that Si or SiO44-, replaces P or PO43-, respectively, at the 6h positions, with the subsequent loss of charge equilibrium.25-28 Several methods for the synthesis of silicon-substituted hydroxyapatites have been described, including the sol-gel method,29 hydrothermal synthesis,30 solidstate reactions,31 and wet methods.32 In this work, we aim to study the incorporation of the silicates in apatites obtained by controlled crystallization process. For this purpose, we have used a silicon alcoxide (TEOS) as the silicon source and the structures of the apatites have been studied. The presence of other substitutions, such as carbonates, is also considered in this work. Experimental Section Samples of pure and silicon-substituted HA were prepared by aqueous precipitation reaction of Ca(NO3)2‚4H2O, (NH4)2HPO4 and Si(CH3CH2O)4, TEOS solutions. The amounts of reactants were calculated on the assumption that silicon would substitute phosphorus. Four different compositions have been prepared with nominal formula Ca10(PO4)6-x(SiO4)x(OH)2-x0x, with x ) 0, 0.25, 0.50, and 1 for samples AP-0, AP-0.25, AP0.5, and AP-1, respectively, and 0 means vacancies at the hydroxyl position. A 1 M solution of Ca(NO3)2‚4H2O was added to (NH4)2HPO4 and TEOS solutions of stoichiometric concentration to obtain the compositions described above. The mixtures were stirred for 12 h at 80 °C. The pH was kept at 9.5 by NH3 solution addition. During the reaction the pH was continuously adjusted to 9.5 to ensure constant conditions during the synthesis. Chemical analysis and FTIR spectroscopy showed that the samples contained an important amount of nitrates coming from the raw materials. For this reason, the samples were treated at 700 °C to remove the nitrates without introducing important changes in the structure and microstructure of the materials. These samples, free of nitrates by thermal treatment at 700 °C, are referred in the text as the “as-prepared samples.” Additionally, a fraction of each asprepared sample was treated at 900 °C for 6 h under air atmosphere. These further heat-treated materials will be referred to in the text as AP-0(900), AP-0.25(900), AP-0.5(900), and AP-1(900). Elemental chemical analysis was carried out by fluorescence X-ray spectrometry for P, Si, and Ca. The C content was determined at the Service Central d’Analyse, CNRS, Vernaison, France. FTIR spectra were obtained with a Nicolet 360 FT-IR spectrometer, using the KBr pellet method. XRD patterns were collected with a Philips PW 1730 X-ray diffractometer using Cu KR radiation (2θ range between 10°-120°, step size 0.02° and 10 seconds of counting time). Rietveld Refinements. Rietveld refinements of the structure were carried out for the four as-prepared samples, as well as for the samples treated at 900 °C. The scale factor, atomic (24) Best, S. M.; Bonfield, W.; Gibson, I. R.; Jha, L. J.; Santos, J. D. International Patent Appl. No. PCT/GB97/02325. (25) Balas, F.; Pe´rez-Pariente, J.; Vallet-Regı´, M. J. Biomed. Mater. Res. 2003, 66A, 364. (26) Gibson, I. R.; Best, S. M.; Bonfield, W. J. Biomed. Mater. Res. 1999, 44, 422. (27) Gibson, I. R.; Best, S. M.; Bonfield, W. J. Am. Ceram. Soc. 2002, 85 (11), 2771. (28) Leventouri, Th; Bunaciu, C. E.; Perdikatsis, V. Biomaterials 2003, 24, 4205. (29) Ruys, A. J. J. Australas. Ceram. Soc. 1993, 29, 71. (30) Tanizawa, Y.; Suzuki, T. J. Chem. Soc., Faraday Trans. 1995, 91, 3499. (31) Boyer, L.; Carpena, J.; Lacout, J. L, Solid State Ionics 1997, 95, 121.
Chem. Mater., Vol. 16, No. 11, 2004 2301 positions, isotropic temperature factors, and patterns parameters (peak widths, cell dimensions, zero shift of 2θ°, background points interpolation, etc.) were also varied. The refinements were performed using the atomic position set and the space group of the HA structure P63/m, No. 1765 by means of the FullProf 2000 computer program.33 The instrumental resolution function (IRF) of the diffractometer was obtained from a very-well-crystallized hydroxylapatite sample and taken into account in a separate input file. The pseudo-Voigt profile function of Thompson, Cox, and Hastings34 was used with an asymmetry correction at low angle. In the first stages of the refinement a disagreement of FWHM for the (0 0 l) reflections, with respect to the IRF was noticed. An important decrease of the Rwp value was obtained after taking into account the crystallite size anisotropy (needle-shaped crystallites). Considering the presence of CO32- in the FTIR results, the refinement proceeded by allowing a simultaneous presence of C and P at the 6h Wyckoff position. The atomic coordinates of C atoms were constrained to be the same as those of P and the occupancy factors were 6 - x and x for P and C, respectively. Notice that all occupancy factors used in this paper are normalized in such a way as to reflect the chemical composition per unit formula. Attempts to introduce C into the initial model for sample AP-0 led to the failure of the refinement. Any attempt to introduce Si atoms in the same position also led to the immediate failure of the refinement, due to the almost identical scattering density factor of the Si and P. The Ca(1), Ca(2), and O(H) occupancies were let to vary freely, whereas the rest of the anionic lattice (O(1), O(2), and O(3)) were fixed to the theoretical occupancy factors. Calculating the distortion of the PO4 tetrahedrons can provide an estimation of the structure distortion. The tetrahedral distortion index was obtained from the calculated data using the relation 6
∑|OTO - OTO i
TDI )
m|
i)1
6
(1)
where OTOi denotes the six angles between P and the four O atoms of the phosphate tetrahedron and OTOm is the average angle (around 109.4°). To calculate the amorphous fraction of the as-prepared samples, additional experiments were done. Exactly-weighted 0.8 g of sample was mixed with 0.2 g of well-crystallized SiO2 used as standard. FullProf calculated the crystalline fractions for the apatite phase, Xap, and the standard phase, Xst, after applying Rietveld analysis. Because only crystalline phases are considered in the refinement by X-ray diffraction data, the mass of the apatite phase, map, is easily calculated using the formula
Xap map ) mst Xst
(2)
where mst is the exact standard mass weighted, that is 0.2 g. The amorphous fraction, mglass, is easily obtained by
mglass ) MT - (map + mst)
(3)
where MT is the total mass (sample plus standard). (32) Gibson, I. R.; Huang, J.; Best, S.M.; Bonfield, W. In Bioceramics, Vol. 12; Ohgushi, H., Hastings, G. W., Yoshikawa, T., Eds.; World Scientific: Singapore, 1999; pp 191-194. (33) Rodrı´guez-Carvajal, J. Physica B 1993, 192, 55. For a more recent version see Rodrı´guez-Carvajal, J. Recent Developments of the Program FULLPROF, in Commission on Powder Diffraction (IUCr), Newsletter 26, 12 19 2001, available at http://journals.iucr.org/iucrtop/comm/cpd/Newsletters/. The complete program and documentation can be obtained from the anonymous ftp-site: ftp://ftp.cea.fr/pub/llb/ divers/fullprof.2k. (34) Thompson, P.; Cox, D. E.; Hastings, J. B. J. Appl. Cryst. 1987, 20, 79.
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Arcos et al.
Table 1. Experimental and Theoretical Cation Content (% in Weight) Obtained by X-ray Fluorescence Spectroscopy sample
Ca
P
Si
C
AP-0 theoretical
39.5 39.9
17.8 18.5
0.0 0.0
