ARTICLE pubs.acs.org/crystal
Effect of Zn2þ on the Physicochemical Characteristics of Octacalcium Phosphate and Its Hydrolysis into Apatitic Phases Yoshitomo Honda,†,§ Takahisa Anada,†,§ Shinji Morimoto,†,§ Yukari Shiwaku,†,‡,§ and Osamu Suzuki*,† † ‡
Division of Craniofacial Function Engineering (CFE), Tohoku University Graduate School of Dentistry, Sendai, Japan Division of Advanced Prosthetic Dentistry, Tohoku University Graduate School of Dentistry, Sendai, Japan ABSTRACT: Zinc (Zn) ions and OCP crystals have both been reported to be stimulants for bone formation. The present study was designed to investigate how Zn ion affects the precipitation of octacalcium phosphate (OCP) and its hydrolysis process into apatitic phases. Zn-containing octacalcium phosphate preparations (Zn-CaPs) and their hydrolysates (hydrolyzed Zn-CaPs) containing various amounts of Zn (0.060.72 mmol/g) were obtained either through a co-precipitation method or by enhancing the OCP hydrolysis in hot water. All of the Zn-CaPs obtained had Ca/P molar ratios similar to that of stoichiometric OCP (1.33), ranging from 1.23 to 1.37. Zn-CaPs also exhibited similar dissolution behavior to that of original OCP if incubated in a physiological solution (in the 0.1 M HEPES buffer, pH = 7.4, 37 °C). X-ray diffraction analysis of the hydrolyzed samples showed that original OCP converted to the crystalline hydroxyapatite with a specific peak at 2θ = 10.8°, while Zn-CaPs containing Zn above the 0.18 mmol/g retained the amorphous-like structure even after a greater than 25 h hydrolysis period. These results indicate that Zn ions retarded the hydrolysis process of OCP toward apatite, resulting in enhanced formation of the amorphous-like structure.
1. INTRODUCTION Recent intensive studies have shown that synthetic octacalcium phosphate (OCP) in the form of granules exhibits prominent osteoconductive16 and biodegradable properties710 at various bone sites. Other studies have also confirmed that an OCP coating on metallic implants raises osteoblastic cell proliferation11 and osteoconductivity more than the original metal surface12 and, in some cases, induces ectopic bone formation.12,13 OCP has been suggested to act as a template for biological apatite crystal formation in bone and tooth,14 although the chemical nature of the first-formed mineral phase has been the subject of a long-standing controversy.1517 The crystal structure of OCP is known to be composed of apatite layers alternately stacked with hydrated layers.14 OCP is a metastable calcium phosphate salt at physiological pH and temperature, and it tends to convert to thermodynamically stable hydroxyapatite (HA) spontaneously and irreversibly.1821 In fact, OCP converts to apatitic phases in in vitro as well as in vivo environments, such as murine tissues, including muscle pouches,18 subcutaneous tissues,22 and various bone sites.1,4,5,22 The conversion from OCP to HA advances through the mechanisms and/or the dissolutionreprecipitation process near the crystal surfaces or topotaxial conversion with ion diffusion within the crystal lattice.14,23 Previous reports have suggested that the process of conversion from OCP to HA may be involved in the stimulatory capacity of OCP in osteoblastic differentiation4 and bone formation.1,4 It has been shown that the conversion of OCP is accompanied by the progressive increase of Ca/P molar ratio and the progressive decrease of acid phosphate19 but not reaching the stoichiometric r 2011 American Chemical Society
composition, resulting in the reduction of crystallinity of OCP and the enhancement of formation of poorly crystallized Cadeficient HA.4 In fact, an OCP that was obtained through partial hydrolysis had a lower crystallinity and facilitated bone formation more compared with the original OCP.6 Thus, it seems likely that OCP is a unique bone substitute material that expresses a stimulatory effect in relation to its structural characteristics. Nevertheless, the osteogenic capability of OCP should be inferior to the graft of autogenous bone, which contains not only osteoblastic cells but also some matrices, such as collagen and apatite crystals. Zinc (Zn) ion is an essential biological trace element that promotes the proliferation and differentiation of osteoblasts,24 while this ion also suppresses the differentiation of osteoclasts.25 Zn-containing calcium phosphate ceramics, such as Zn-β-tricalcium phosphate/HA (Zn-β-TCP/HA), were first developed to bring about better osteoconductive characteristics than the original calcium phosphate materials.26 More recently, a number of Zn-containing ceramics, such as Zn-HA,27 Zn-containing organoapatite,28 Zn-containing glasses,29 and Zn-containing calcium phosphate cements,30 were fabricated for medical use. However, the effect of Zn ion on OCP preparation and hydrolysis has never been examined from the point of view of the fabrication of bone substitute material, although the inhibitory effect of OCP crystal nucleation and growth has already been reported.31 Received: July 25, 2010 Revised: February 23, 2011 Published: March 25, 2011 1462
dx.doi.org/10.1021/cg1009835 | Cryst. Growth Des. 2011, 11, 1462–1468
Crystal Growth & Design
ARTICLE
Table 1. Chemical Composition of Zn-CaPs Zn concentration in initial
Ca
P
Zn
samples
synthesis solution (mM)
(mmol/g)
(mmol/g)
(mmol/g)
Ca/P
(ZnþCa)/P
Zn/(ZnþCa) molar ratio
molar ratio
molar ratio
Zn(0.0)-CaP
0.0
7.96
6.10
Zn(0.4)-CaP
0.4
7.78
6.33
0.06
0.00
1.30
1.30
0.72
1.23
Zn(0.9)-CaP
0.9
7.93
6.07
1.24
0.13
1.63
1.31
Zn(1.3)-CaP
1.3
7.93
1.33
6.04
0.18
2.26
1.31
Zn(1.8)-CaP
1.8
1.34
7.63
5.55
0.30
3.76
1.37
Zn(2.6)-CaP
1.43
2.6
7.24
5.26
0.43
5.55
1.37
Zn(3.5)-CaP
1.46
3.5
6.99
5.13
0.61
7.98
1.36
1.48
The goal of the present study was to characterize the physicochemical properties of Zn-containing OCPs and hydrolyzed Zn-containing OCPs (Zn-calcium phosphate (Zn-CaPs) and hydrolyzed Zn-CaPs hereafter). There is a paucity of evidence to show how Zn ion regulates the conversion process of OCP into HA, thereby affecting the physicochemical properties, such as the chemical composition and the structure, which could be factors that affect osteoconductivity of these materials if used.
2. MATERIALS AND METHODS Zn-CaPs containing various amounts of Zn were prepared applying the OCP-synthesis method as reported previously.1 Briefly, 1 L of calcium acetate solutions containing 0.0, 0.4, 0.9, 1.3, 1.8, 2.6, and 3.5 mM Zn ions was mixed with 1 L of stirred sodium phosphate solutions at 70 °C. The prepared Zn-CaPs are hereafter referred to as Zn(0.0)-CaP, Zn(0.4)-CaP, Zn(0.9)-CaP, Zn(1.3)-CaP, Zn(1.8)-CaP, Zn(2.6)-CaP, and Zn(3.5)-CaP, respectively, in agreement with the initial Zn concentration in synthesis solution. The precipitates were washed 2 times using 2 L of purified water in order to exclude the redundant Zn ions. As for hydrolyzed Zn-CaP, the total amount of washed Zn-CaPs at each synthesis was subsequently incubated in 3.5 L of 70 °C hot pure water with constant stirring up to a maximum of 39 h. It is known that OCP converts into the apatite structure at a physiological condition of approximately 37 °C. However, because the conversion of well-grown OCP crystals requires more time to complete, we used the hydrolysis method in hot water to accelerate the conversion from OCP to HA. The precipitates were filtered to discard the excessive Zn and then dried at 105 °C for further analysis. Although it is known that as the heating temperature rises up to 150 °C from around 100 °C, the dehydration of OCP advances, resulting in the collapse of OCP structure,14 our previous results showed that heating around 100 °C does not affect the physical properties, such as X-ray diffraction (XRD) profiles, of OCP.22,32 The powder XRD patterns of the precipitates were obtained using a Miniflex (Rigaku Co., Tokyo, Japan) at step scanning of 0.5° min1 and 0.02° intervals from 3.5° to 60.0°, with Cu KR X-ray radiation at 30 kV and 15 mA. The obtained XRD patterns were analyzed by comparing them with ICDD numbers 79-423 for OCP, 9-432 for HA, 20-1435 for Zn(OH)2, and 65-0682 for ZnO to identify the crystalline phases. The infrared spectra of the precipitates were obtained by means of Fourier transform infrared (FTIR) spectroscopy using the FREEXACT-2 (HORIBA, Kyoto, Japan) and the FT/IR6300 (JASCO, Tokyo, Japan). The samples were diluted with KBr and were analyzed over the range of 1300500 cm1 with 4 cm1 resolution. The chemical compositions of the Zn-CaPs and hydrolyzed Zn-CaPs were determined using an ICPS8000 inductively coupled plasma (ICP) spectroscope (Shimadzu, Kyoto, Japan), which analyzed the supernatant of completely dissolved samples in hydrochloric acid. The morphologies of samples were analyzed by scanning electron microscopy (SEM) using a JSM-6390LA (JEOL, Tokyo, Japan) on low magnification. For high magnification, the SEM
images were obtained using a field emission scanning electron microscope (FE-SEM; S-4000, Hitachi Ltd., Tokyo, Japan). The dissolution behavior of the Zn-CaPs and hydrolyzed-Zn-CaPs in 0.1 M HEPES buffer (pH = 7.4) at 37 °C, after the 2.5 h incubation, was evaluated by measuring the change of the inorganic phosphate (Pi) ion concentrations. It was determined by means of colorimetrical methods using a commercially available PhosphaC-test Wako kit (Wako Pure Chemical Industries, Osaka, Japan). Solid/liquid ratio of a 1 g/L was used for all samples. The results are expressed as the mean ( standard deviation (n = 3). This dissolution test was carried out with three replicates, and it showed reliable reproducibility.
3. RESULTS 3.1. Characterization of Zn-CaPs. The chemical composition of the Zn-CaPs synthesized by means of the co-precipitation method is summarized in Table 1. The Zn content and Zn/(CaþZn) molar ratio in the precipitates increased depending on the initial Zn concentrations in the synthesis solution. The Ca/P molar ratios of Zn-CaPs were in a range close to the stoichiometric composition of OCP (Ca/P = 1.33). Those (ZnþCa)/P molar ratios in Zn-CaP up to that of Zn(1.3)-CaP also were kept around that of OCP. Typical XRD patterns before hydrolysis of Zn-CaPs are shown in the upper part of the Figure 1a. The reflection peaks of OCP (2θ = 4.9°, 100; 9.6°, 200; 9.9°, 010; and 33.7°, 700) were found in the Zn(0.0)-CaP and in those from the Zn(0.4)-CaP to the Zn(1.3)-CaP. The peak of well-crystallized HA (2θ = 10.8°) was not observed in all Zn-CaPs. No crystalline phases originating from Zn-related crystals, such as Zn(OH)2 and ZnO were detected from the XRD reflection peaks in any of the Zn-CaPs. The strongest peaks of OCP (2θ = 4.9°, 100) became broader with increasing Zn contents in the synthesis solution, suggesting that the structure of OCP tends to change to that of the amorphous-like apatitic phase. The FTIR spectra of Zn-CaPs containing different amounts of Zn are shown in Figure 2a. Two sharp adsorption bands of ν4 PO4 at 500600 cm1 were attributed to crystalline CaP.33 Sharp PO bands at 1039, 1077, and 1108 cm1 ascribed to PO4 and HOPO3 stretching modes of the ν3 type of the OCP structure were observed in the spectra of the Zn(0.0)-CaP. The peaks at 1077 and 1108 cm1 diminished according to the increase of Zn content. The morphologies of the Zn-CaPs observed by means of SEM and FE-SEM are shown in Figure 3. Zn(0.0)-CaP (intact OCP samples) showed a platy morphology in the range of 110 μm in length, which was identical to that in the OCP samples reported previously.19 The plate-like morphology of OCP changed into sphere-like and flake-like morphology with increasing the Zn content. It seemed unlikely that each crystal at the Zn-CaPs 1463
dx.doi.org/10.1021/cg1009835 |Cryst. Growth Des. 2011, 11, 1462–1468
Crystal Growth & Design
ARTICLE
Figure 1. Overview (a) and magnified (b) powder XRD patterns of Zn-CaPs and hydrolyzed Zn-CaPs. The squares in the patterns in panel a represent the magnified area. Each Zn-CaP was hydrolyzed up to 28 h for Zn(0.0)-CaP, 35 h for Zn(0.4)-CaP, 39 h for Zn(1.3)-CaP, and 38 h for Zn(3.5)-CaP. The obtained XRD patterns were identified by comparing them with ICDD numbers 79-423 for OCP and 9-432 for HA. The major reflection peaks of OCP are indicated in the XRD profiles by the asterisk (/). Arrows represent the peaks of well-crystallized HA (2θ = 10.8°, 100). 1464
dx.doi.org/10.1021/cg1009835 |Cryst. Growth Des. 2011, 11, 1462–1468
Crystal Growth & Design
ARTICLE
longer than that of Zn(0.0)-CaP, the characteristic peaks of wellcrystallized HA (2θ = 10.8°, 100) were broadened in those hydrolysates, which displayed the XRD patterns of amorphouslike apatite compared with those of Zn(0.0)-CaP and Zn(1.3)CaP. Figure 1b represents the magnified XRD patterns of the ZnCaPs and 4 h hydrolyzed Zn-CaPs in the 2θ range of 812°. A characteristic peak of HA (2θ = 10.8°, 100) was less detectable with increasing Zn content. In contrast, the appearance of characteristic OCP peaks (2θ = 9.6° and 9.9°) was preserved in the XRD patterns of Zn-CaPs containing high amounts of Zn ions. No obvious changes were observed in the XRD profiles of the Zn(3.5)-CaP. The data indicated that the Zn ions are involved in the conversion of OCP into HA and play a role in delaying the process. FTIR spectra of the 4 h hydrolyzed Zn-CaPs are shown in Figure 2b. The characteristic peaks of the OCP samples, 1077 cm1, became obscured in the Zn(0.0)-CaP (without Zn ions), while those of OCPs containing low amounts of Zn ions remained unchanged. The Ca/P molar ratio, Zn content, and Zn/(ZnþCa) molar ratio of Zn-CaPs and hydrolyzed-Zn-CaPs are summarized in Table 2. It has been reported that the Ca/P ratio of the samples increases with advancing conversion process from OCP to HA, accompanied by Ca incorporation into the crystals and inorganic phosphate release from the crystals into the surrounding solution.4,34 The Ca/P molar ratio of all ZnCaPs increased with advancing conversion process regardless of the Zn content in the Zn-CaPs, although these values did not reach those of the stoichiometric composition of HA (Ca/P = 1.67), indicating the characteristics of Ca-deficient HA. The XRD patterns of Zn(3.5)-CaPs before and after the hydrolysis were in an amorphous-like apatitic phase even when its Ca/P molar ratio increased progressively from 1.36 to 1.45. The Zn content and Zn/(ZnþCa) molar ratio of all the Zn-CaPs increased depending on the advancement of hydrolysis. Pi concentration, which could be associated with the dissolution behavior, is denoted in Figure 4. The Pi concentration of all Zn-CaPs was higher than that of hydrolyzed-Zn-CaPs. Interestingly, although the XRD profile of the Zn(3.5)-CaP showed that of an amorphous-like apatite, the dissolution behavior was compatible to that of the original OCP. The dissolution of Zn(3.5)-CaP was much higher than that of hydrolyzed Zn(3.5)-CaP, although the characteristics of the structure analyzed by XRD were similar. The dissolution of partial hydrolyzed ZnCaPs (4 h hydrolyzed products) was still higher than that of >25 h hydrolyzed Zn-CaP. Figure 2. FTIR spectra of Zn-CaPs (a) and 4 h hydryolyzed Zn-CaPs (b). The arrows represent the characteristic OCP peaks of 1077 and 1108 cm1.
containing a high amount of Zn could be recognized even at a higher magnification (50000) (Figure 3b). 3.2. Effect of the Hydrolysis on the Physicochemical Properties of the Zn-CaPs. The XRD patterns of Zn-CaPs hydrolyzed for 4 h and for 2539 h in 70 °C pure water are shown in lower part of a and panel b in Figure 1. In accordance with the advancement of the conversion process, the characteristic OCP peaks in all Zn-CaPs (without Zn(3.5)-CaP) tended to disappear. After hydrolysis for 28 and 35 h, the characteristic HA peaks (2θ = 10.8°, 100) became detectable in the XRD patterns of Zn(0.0)-CaP and Zn(0.4)-CaP, suggesting that they were transformed into well-crystallized HA. On the other hand, although the hydrolysis of Zn(1.3)-CaP and Zn(3.5)-CaP took
4. DISCUSSION The results revealed that Zn ions contained in the Zn-CaPs increased according to the initial Zn concentration in the synthesis solution on the basis of the chemical composition, showing a progressive increase of the Zn/(CaþZn) molar ratio which suggests that Zn ions are present in association with OCP and its hydrolyzed apatitic crystals. It is also notable that these Zn ions indeed control the conversion kinetics from Zn-CaP to hydrolyzed Zn-CaP. Concerning the structure of Zn-CaP, the current work showed that a feature of OCP was retained even when the inclusion of Zn ions increased to approximately 0.61 mmol/g, although the XRD reflection and FTIR spectra of the samples did not indicate those of the single phase of OCP but, rather, were similar to those of amorphous-like apatitic phase. Nevertheless, the Ca/P molar ratio of all Zn-CaPs remained in the range between 1.23 and 1.37, 1465
dx.doi.org/10.1021/cg1009835 |Cryst. Growth Des. 2011, 11, 1462–1468
Crystal Growth & Design
ARTICLE
Figure 3. SEM (a) and FE-SEM (b) micrograph of Zn-CaPs. Bar = 2 μm (a) and 600 nm (b). Arrows represent the platy OCP crystals.
Table 2. Ca/P Molar Ratio, Zn Content, and Zn/(ZnþCa) Molar Ratio of the Zn-CaPs and Hydrolyzed Zn-CaPs Ca/P molar ratio
Zn content (mmol/g)
Zn/(ZnþCa) molar ratio
original samples
original
hydrolysis 4 h
hydrolysis >25 h
original
hydrolysis 4 h
hydrolysis >25 h
original
hydrolysis 4 h
hydrolysis >25 h
Zn(0.0)-CaP Zn(0.4)-CaP
1.30 1.23
1.49 1.40
1.53 1.54
0.06
0.07
0.09
0.72
0.81
1.01
Zn(0.9)-CaP
1.31
1.37
1.51
0.13
0.16
0.19
1.63
1.88
2.06
Zn(1.3)-CaP
1.31
1.44
1.50
0.18
0.25
0.33
2.26
2.87
3.70
Zn(1.8)-CaP
1.37
1.47
0.30
0.36
3.76
3.98
Zn(2.6)-CaP
1.37
1.44
0.43
0.50
5.55
6.18
Zn(3.5)-CaP
1.36
1.42
0.61
0.67
7.98
8.12
1.45
0.72
8.44
Figure 4. Dissolution behavior of the Zn-CaPs and hydrolyzed Zn-CaPs in 0.1 M HEPES buffer (pH = 7.4) at 37 °C. Solid/liquid ratio = 1 g/L for all samples.
showing values close to those of stoichiometric OCP (1.33) (Table 1). Mathew et al. suggested that a nonstoichiometric OCP structure with excess hydrogen would resemble the structure of HA.35 In fact, a recent study reported that the partial hydrolysis of OCP with a Ca/P molar ratio of 1.23 in hot water produces a nonstoichiometric and low-crystalline OCP with a Ca/P molar ratio of 1.37.6 It is likely that the prepared Zn-CaPs have the characteristics of OCP because these samples not only
had a Ca/P molar ratio corresponding to that of OCP but also exhibited a higher dissolution tendency than the hydrolyzed apatitic products of Zn-CaPs (Figure 4). The results of the hydrolysis of Zn-CaPs in 70 °C suggest that Zn in the OCP possibly regulates the conversion process. Previous studies demonstrated that the hydrolysis of OCP proceeds through a solid-state topotaxial transition within the crystals themselves, accompanied by a release of water molecules, 1466
dx.doi.org/10.1021/cg1009835 |Cryst. Growth Des. 2011, 11, 1462–1468
Crystal Growth & Design
ARTICLE
hydrogen ions, and approximately 20% of the PO4 ions.4,19,34 When Zn-CaPs, including Zn(3.5)-CaPs, were hydrolyzed in hot pure water, the Ca/P molar ratios of Zn-CaPs increased up to approximately 1.54 with time (Table 2). The increment of the Ca/P molar ratios by the hydrolysis confirmed the promotion of the conversion of Zn-CaP into apatitic phases, even in Zn(3.5)CaP, but the hydrolysis yielded only amorphous-like apatitic products with a higher Ca-deficiency in their structure compared with the stoichiometric ratio of HA (1.67). A nonstoichiometric formula for OCP, Ca16H4þx(PO4)12(OH)x 3 (10 x)H2O, has been proposed.35 Although we did not determine the amount of hydrogen and hydroxyl ions, the chemical formula for Zn-CaPs could be expressed based on the chemical composition and the structural information, according to this stoichiometric model: Ca7:78 Zn0:06 Hð4 þ xÞ=2 ðPO4 Þ6:33 ðOHÞx=2 3 ð10 xÞ=2 3 H2 O ð1Þ When the structure of HA is assumed as the synthesis product, the nonstoichiometric compositions, assuming Ca-deficient HA, Ca10xHx(PO4)6(OH)2x, where 0 e x e 236 can be calculated as follows, although the excessive x value beyond 2 should be compensated by cationic ions other than Ca and Zn: Ca7:00 Zn0:61 Hx ðPO4 Þ5:13 ðOHÞ2 x
ð2Þ
The formation of the apatitic products from these Zn-CaPs if hydrolyzed could be advanced through the dissolutionreprecipitation reaction20,34 or the ripening process of the apatite crystals34,37on the OCP or the apatite seed templates containing Zn ions. The resultant products could again be the nonstoichiometric formula as follows: Ca9:18 Zn0:09 Hx ðPO4 Þ5:97 ðOHÞ2 x
ð3Þ
Ca7:83 Zn0:72 Hx ðPO4 Þ5:39 ðOHÞ2 x
ð4Þ
It is well accepted that OCP is more soluble than HA at neutral pH.38 Unexpectedly, the dissolution of Zn(3.5)-CaP, before the hydrolysis, as evaluated by the Pi concentration in 0.1 M HEPES buffers, was higher than that of the hydrolyzed products. A thermodynamic analysis study of the formation of HA from a supersaturated solution by Eeans et al. suggested that HA is formed from an OCP-like phase that lacks the specific peaks of this salt in XRD.39 The results suggest that the intrinsic physicochemical nature of OCP regarding the chemical composition and the dissolution is retained. The inclusion of Zn into the present synthesized Zn-CaP bulk retarded the crystallization of HA during the hydrolysis for 39 h (Figure 1 and 2), yielding poorly crystallized amorphous-like HA while retaining a distinct HA peak in XRD (100). The inhibitors of HA formation reported so far are cations, such as magnesium ions40 and Zn ions,31 which are interpreted to work as adsorbate ions for the crystal growth site (Ca site) in the HA surface and compete with Ca ions to be adsorbed onto the site, thereby interfering with the crystal growth by Ca and phosphate ions.
5. CONCLUSION Zn-CaPs were obtained by using co-precipitation methods. Zn-CaPs retained OCP-like characteristics in regard to the stoichiometry and dissolution behavior. The presence of Zn in OCP controlled the kinetics of the hydrolysis from OCP to HA
and facilitated the formation of amorphous-like apatitic crystals. Further study is underway to determine the localization of Zn ions in the OCP and the apatitic crystals and the efficacy of the Zn-CaPs to stimulate bone formation with Zn ions present in the crystals.
’ AUTHOR INFORMATION Corresponding Author
*Mailing address: Division of Craniofacial Function Engineering (CFE), Tohoku University Graduate School of Dentistry, 4-1, Seiryo-machi, Aoba-ku, Sendai 980-8575, JAPAN. Tel: þ81-22-717-7635. Fax: þ81-22-717-7637. E-mail address:
[email protected]. Notes §
Author’s e-mail addresses: Y.H.,
[email protected]; T. A.,
[email protected]; S.M.,
[email protected]; Y.S.,
[email protected].
’ ACKNOWLEDGMENT We thank H. Kubota and A. Harada of the Tohoku University School of Dentistry for their cooperation in the preparation of Zn-CaPs. This study was supported in part by Grants-in-Aid (Nos. 17076001, 19390490, 20659304, 21659452, and 21591910) from the Ministry of Education, Science, Sports, and Culture of Japan. ’ REFERENCES (1) Suzuki, O.; Nakamaura, M.; Miyasaka, Y.; Kagayama, M.; Sakurai, M. Tohoku J. Exp. Med. 1991, 37–50. (2) Sasano, Y.; Kamakura, S.; Nakamura, M.; Suzuki, O.; Mizoguchi, I.; Akita, H.; Kagayama, M. Anat. Rec. 1995, 242, 40–46. (3) Kamakura, S.; Sasano, Y.; Homma, H.; Suzuki, O.; Kagayama, M.; Motegi, K. J. Dent. Res. 1999, 78, 1682–1687. (4) Suzuki, O.; Kamakura, S.; Katagiri, T.; Nakamura, M.; Zhao, B.; Honda, Y.; Kamijo, R. Biomaterials 2006, 27, 2671–2681. (5) Honda, Y.; Anada, T.; Kamakura, S.; Morimoto, S.; Kuriyagawa, T.; Suzuki, O. Tissue Eng., Part A 2009, 15, 1965–1973. (6) Miyatake, N.; Kishimoto, K. N.; Anada, T.; Imaizumi, H.; Itoi, E.; Suzuki, O. Biomaterials 2009, 30, 1005–1014. (7) Sugihara, F.; Oonishi, H.; Minamigawa, K.; Mandai, Y.; Tshuji, E.; Yoshikawa, M.; Toda, T. Bioceramics 1996, 9, 339–402. (8) Imaizumi, H.; Sakurai, M.; Kashimoto, O.; Kikawa, T.; Suzuki, O. Calcif. Tissue Int. 2006, 78, 45–54. (9) Kikawa, T.; Kashimoto, O.; Imaizumi, H.; Kokubun, S.; Suzuki, O. Acta Biomater. 2009, 5, 1756–1766. (10) Takami, M.; Mochizuki, A.; Yamada, A.; Tachi, K.; Zhao, B.; Miyamoto, Y.; Anada, T.; Honda, Y.; Inoue, T.; Nakamura, M.; Suzuki, O.; Kamijo, R. Tissue Eng., Part A 2009, 15, 3991–4000. (11) Bigi, A.; Bracci, B.; Cuisinier, F.; Elkaim, R.; Fini, M.; Mayer, I.; Mihailescu, I. N.; Socol, G.; Sturba, L.; Torricelli, P. Biomaterials 2005, 26, 2381–2389. (12) Habibovic, P.; Yuan, H.; van der Valk, C. M.; Meijer, G.; van Blitterswijk, C. A.; de Groot, K. Biomaterials 2005, 26, 3565–3575. (13) Barrere, F.; van der Valk, C. M.; Dalmeijer, R. A.; Meijer, G.; van Blitterswijk, C. A.; de Groot, K.; Layrolle, P. J. Biomed. Mater. Res. A. 2003, 66, 779–788. (14) Brown, W. E.; Smith, J. P.; Lehr, J. R.; Frazier, A. W. Nature 1962, 196, 1048–1055. (15) Crane, N. J.; Popescu, V.; Morris, M. D.; Steenhuis, P.; Ignelzi, M. A., Jr. Bone 2006, 39, 434–442. (16) Weiner, S. Bone 2006, 39, 431–433. (17) Grynpas, M. D.; Omelon, S. Bone 2007, 41, 162–164. 1467
dx.doi.org/10.1021/cg1009835 |Cryst. Growth Des. 2011, 11, 1462–1468
Crystal Growth & Design
ARTICLE
(18) Ban, S.; Jinde, T.; Hasegawa, J. Dent. Mater. J. 1992, 11, 130–140. (19) Suzuki, O.; Yagishita, H.; Yamazaki, M.; Aoba, T. Cells Mater. 1995, 5, 45–54. (20) LeGeros, R.; Daculsi, G.; Orly, I.; Abergas, T.; Torres, W. Scanning Microsc. 1989, 3, 129–137. (21) Tomaxic, B.; Tung, M.; Gregory, T.; Brown, W. Scanning Electron Microsc. 1989, 3, 119–127. (22) Suzuki, O.; Nakamura, M.; Miyasaka, Y.; Kagayama, M.; Sakurai, M. Bone Miner. 1993, 20, 151–166. (23) Tung, M. S.; Tomazic, B.; Brown, W. E. Arch. Oral Biol. 1992, 37, 585–591. (24) Hall, S. L.; Dimai, H. P.; Farley, J. R. Calcif. Tissue Int. 1999, 64, 163–172. (25) Kishi, S.; Yamaguchi, M. Biochem. Pharmacol. 1994, 48, 1225–1230. (26) Ito, A.; Ojima, K.; Naito, H.; Ichinose, N.; Tateishi, T. J. Biomed. Mater. Res. 2000, 50, 178–183. (27) Miyaji, F.; Kono, Y.; Suyama, Y. Mater. Res. Bull. 2005, 40, 209–220. (28) Storrie, H.; Stupp, S. I. Biomaterials 2005, 26, 5492–5499. (29) Salih, V.; Patel, A.; Knowles, J. C. Biomed. Mater. 2007, 2, 11–20. (30) Ishikawa, K.; Miyamoto, Y.; Yuasa, T.; Ito, A.; Nagayama, M.; Suzuki, K. Biomaterials 2002, 23, 423–428. (31) LeGeros, R. Z.; Bleiwas, C. B.; Retino, M.; Rohanizadeh, R.; LeGeros, J. P. Am. J. Dent. 1999, 12, 65–71. (32) Suzuki, O.; Yagishita, H.; Amano, T.; Aoba, T. J. Dent. Res. 1995, 74, 1764–1769. (33) Fowler, B. O.; Moreno, E. C.; Brown, W. E. Arch. Oral Biol. 1966, 11, 477–492. (34) Brown, W.; Mathew, M.; Tung, M. Progr. Cryst. Growth Char. 1981, 4, 59–87. (35) Mathew, M.; Brown, W.; LW, S. J. Crystallogr. Spectrosc. Res. 1988, 18, 235–250. (36) Winand, L. Physico-chemical study of some apatitic calcium phosphates. In Tooth Enamel; Stack M. V., Fearnhead, R. S., Eds.; John Wright and Sons: Bristol, U.K., 1965; pp 1519. (37) Nancollas, G. H.; Wefel, J. S. J. Dent. Res. 1976, 55, 617–624. (38) Heughebaert, J. C.; Nancollas, G. H. J. Phys. Chem. 1984, 88, 2478–2481. (39) Eanes, E. D.; Meyer, J. L. Calcif. Tissue Res. 1977, 23, 259–269. (40) Aoba, T.; Moreno, E. C.; Shimoda, S. Calcif. Tissue Int. 1992, 51, 143–150.
1468
dx.doi.org/10.1021/cg1009835 |Cryst. Growth Des. 2011, 11, 1462–1468
