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Preparation of pore expanded mesoporous hydroxyapatite via auxiliary solubilizing template method
Colloids and Surfaces A: Physicochem. Eng. Aspects 441 (2014) 737–743
Contents lists available at ScienceDirect
Colloids and Surfaces A: Physicochemical and Engineering Aspects journal homepage: www.elsevier.com/locate/colsurfa
Preparation of pore expanded mesoporous hydroxyapatite via auxiliary solubilizing template method Fanyan Zeng c , Jing Wang c,∗ , Yi Wu c , Yuanman Yu c , Wei Tang c , Manli Yin c , Changsheng Liu a,b,c,∗∗ a
The State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai 200237, PR China Key Laboratory for Ultrafine Materials of Ministry of Education, East China University of Science and Technology, Shanghai 200237, PR China c Engineering Research Center for Biomedical Materials of Ministry of Education, East China University of Science and Technology, Shanghai 200237, PR China b
h i g h l i g h t s
g r a p h i c a l
a b s t r a c t
• CTAB and TMB were used as soft • • • •
template and pore expanding agent, respectively. Average length of the as-synthesized HAp nanoparticles is 50–150 nm. Large amount of mesoporous spread around the surface of mesoHAp nanorods. The shape of mesopores was elongated and opened at both extremities. Pore diameter of mesoHAp was up to 15 nm, indicating the pore enlargement of TMB.
a r t i c l e
i n f o
Article history: Received 23 April 2013 Received in revised form 7 September 2013 Accepted 1 October 2013 Available online 16 October 2013 Keywords: Mesoporous materials Hydroxyapatite Soft-tempalte Pore expanding agent Micelles
a b s t r a c t Here we present a facile approach to prepare pore-expanding mesoporous hydroxyapatite (mesoHAp) using solubilized micelle template. 1,3,5-rimethy benzene (TMB) was selected as auxiliary solubilizer together with the general soft template cetyltrimethylammonium bromide (CTAB). Enlarged mesoporous can be obtained through the swelling of micelle. Numerous individual nano channels can be observed under TEM images spreading and penetrating within the mesoHAp nanorods. Compared to the mesoHAp without TMB, the channels have enlarged dimensions of about 5–15 nm and the space between the nano channels are filled with an ordered crystalline HAp structure with typical hexagonal crystals. A probable mechanism is that TMB can enter into the amphiphilic CTAB micelle to form swelled TMB/CTAB-PO4 3− complex, and in the presence of Ca2+ , Ca9 (PO4 )6 clusters are preferentially condensed on the micelle surface due to the conformation compatibility between the identical hexagonal shapes of the micelles and Ca9 (PO4 )6 . Interesting, the pore size distribution of mesoHAp was centered at ∼4.7 nm and ∼10 nm, which might be arisen from the coexistence of both unsolubilized CTAB micelles and solubilized TMB/CTAB micelles. The pore-enlarged mesoHAp nanoparticles presented a platform for protein delivery system and might be applicable in biocomposite scaffold for bone regeneration. © 2013 Elsevier B.V. All rights reserved.
1. Introduction ∗ Corresponding author. ∗∗ Corresponding author at: Engineering Research Center for Biomedical Materials of Ministry of Education, East China University of Science and Technology, Shanghai 200237, PR China. E-mail addresses: [email protected] (F. Zeng), [email protected] (J. Wang), [email protected] (C. Liu). 0927-7757/$ – see front matter © 2013 Elsevier B.V. All rights reserved. http://dx.doi.org/10.1016/j.colsurfa.2013.10.028
Recently, the synthesis of inorganic mesoporous materials has attracted much attention in chemistry and materials communities because of their low density, large specific area and pore volume, small size, mechanical and thermal stabilities, and surface permeability [1–3]. Up to now, a variety of mesoporous materials have
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been developed including the representative mesoporous silicabased molecular sieves, such as SBA and MCM. As one of the most energetic research areas in materials science [4], mesoporous silicabased nanoparticles (MSNs) have variety of potential applications in cosmetic, catalysis, coatings, composite materials, dyes, ink, artificial cells and fillers [5–8], etc. Despite the hot topic, silica-based mesoporous materials may not be suitable for tissue regeneration in vivo since its vague biological response. Hydroxyapatite (Ca10 (PO4 )6 (OH)2 , HAp), the major inorganic component of bone and teeth, is a key biomaterial in potential orthopedic [9], dental, and maxillofacial therapies because of the excellent biocompatibility, bioactivity, and osteoconductivity [10–13]. Moreover, it is worth noting that mesoporous HAp (mesoHAp) nanoparticles have greater potential in drug delivery systems, due to the distinct advantages of highly ordered mesoporous structure, large surface area and porosity that provide excellent loading capacity and releasing profile. Therefore, mesoHAp can be incorporated into scaffolds for the beneficial effects of improving osteogenesis and delivery of biologically active molecules [14]. However, despite their favorable properties, fabrication of mesoHAp with higher surface area is difficulty owing to its preferable crystallization in aqueous solution and then cannot interact with surfactant molecules. According to the literature, most of mesoporous calcium phosphate has the surface areas of 20–60 m2 g−1 . Another challenge lies in the relative smaller pore diameters less than 5 nm [15], whereas most cytokines are 8 nm or larger [16–18]. Therefore, a number of studies have been focused on the improvement of the pore diameter of mesoHAp [16,19,20]. Various techniques have been utilized to fabricate mesoHAp, including sol–gel method [19], hydrothermal method [16], microemulsion process [20] and co-precipitation technique [21], there into the templating method is regarded as the most valid approach to obtain mosoHAp. A series of surfactants, including pluronic P123 [22,23], sodium dodecyl sulfate (SDS) [24], non-ionic block co-polymer pluronic F127 [25,26] and cetyltrimethylammonium bromide (CTAB) [15,27], have been used as templates for synthesis of mesoporous materials. For example, Coelho et al. [27] synthesized HAp nanorods using CTAB and the effect of the sintering temperature on its nanostructure was studied. Li et al. [15] synthesized HAp using CTAB and studied the impact of reaction temperature and CTAB/PO4 3− ratio on its thermostability. However, most of these studies are focus on the improvement of stability of HAp, the efficient strategy of mesoporous pore size enlargement is still defective. Therefore, synthesis of large pore size mesoHAp is an extremely promising research. In recent research of ordered mesoporous siliceous materials, additional organic molecules have been appended to the template to achieve pore-expanding [28]. Inspired by this method, an alkylated benzene hydrocarbons, 1,3,5-trimethy benzene (TMB) is involved combined with the general soft template CTAB. The auxiliary TMB is conductive to the enlargement of pore diameter of mesoHAp through the micellar solubilization. The physicochemical properties are investigated, and the possible mechanism of pore size expanding is proposed.
to adjust the pH to 12). Then, 4.44 g of CaCl2 was directly added into 60 mL H2 O to form solution 2. After vigorously stirring and ultrasonication respectively until optically transparent, solution 2 was introduced into the well-dispersed solution 1drop by drop. The reactant molar ratio of Ca2+ /PO4 3− was kept at 1.67. After additional agitation at ambient temperature and normal atmospheric pressure for 3 h, the as-obtained mixing solution was refluxed at 120 ◦ C for 48 h to remove the template of CTAB and TMB, followed by cooling to room temperature naturally. Finally, the precipitate was separated by centrifugation and washing with deionized water and ethanol for six times repeatedly, and dried in vacuum at 60 ◦ C for 24 h, then calcined in a furnace at 550 ◦ C for 6 h to obtain the final mesoHAp (denote as S3). The samples synthesized without TMB (denote as S2) and without template (nHAp, denote as S1) were used as control. 2.2. Characterization The wide-angle ( from 10 to 100◦ ) and small-angle ( from 0 to 5◦ ) XRD patterns were recorded by using a SHIMADZU model XRD6000 X-ray powder diffractometer (Cu K␣ radiation, 40 kV, 30 mA and a scanning speed 2.08 (2)/min). Fourier transform infra-red (FTIR) spectrum was collected on a FTIT-AVATAR370 spectrophotometer over the range of wavenumber 4000–300 cm−1 using KBr pellet. Morphologies were examined via a field-emission-type scanning electron microscope (FSEM, SIRION-100). Transmission electron microscope (TEM) images were obtained on a JEOL-2010 Electron Microscope with an acceleration voltage of 120 kV N2 adsorption/desorption analysis was performed at 77 K using a Quantachrome Quadrasorb SI apparatus. The specific surface area was determined by the Bruaauer–Emmett–Teller (BET) method, the pore parameters (pore volume and pore diameter) were evaluated from the desorption branch of isotherm based on Barrett–Joyner–Halenda (BJH) model.
3. Results 3.1. X-ray diffractions The wide-angle XRD patterns of the obtained samples (S1, S2 and S3) were shown in Fig. 1A. All the diffraction peaks of the three samples corresponded to the standard characteristic peaks of HAp (JCPDS card: No. 24-0033), indicating that the phase of the samples was highly pure HAp. Small-angle (2 < 5◦ ) XRD diffraction was used to verify the existence of long-range ordered structure inside the samples [26]. As shown in Fig. 1B, S1 exhibited a smooth curve compared to S2 and S3. However, numerous peaks and background appeared in the XRD pattern of S2 and S3, especially from 2 to 4◦ , indicating irregular mesoporous structures existed in S2 and S3. Furthermore, no significant difference was observed between S2 and S3 from Fig. 1B. 3.2. FT-IR spectroscopy
2. Experimental 2.1. Materials and synthesis procedure The procedure employed for the synthesis of HAp nanorods was as follows and all reagents were of analytical grade, purchased from Shanghai Chemical Co., Ltd., PR China and used with no further purification. In a typical procedure, 5.48 g of K2 HPO4 ·3H2 O, 8.74 g of CTAB, and 2.88 g of TMB were dispensed in deionized water to form 100 mL solution 1 (1 M sodium hydroxide solution was used
Fig. 2 shows the FTIR spectra of the three samples. For S3, phosphate absorption bands occurred at 474, 563, 964, 1032 and 1092 cm−1 , and the hydroxyl absorption bands at 3572 and 634 cm−1 were characteristic of a typical characteristic absorptions of hydroxyapatite [29]. The peaks at 3433 and 1639 cm−1 were assigned to the bending mode of the adsorbed water [30]. The two sharp and weak peaks at 721, 2854 and 2924 cm−1 were attributed to the residual of CTAB [17]. No trace of TMB was observed from the FTIR spectra, indicating TMB was removed cleanly after the high temperature refluxing, repeated washing and calcining.
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Table 1 The textural parameters of samples analyzed with nitrogen adsorption–desorption method: (S1) nHAp, (S2) M-1-mesoHAp and (S3) M-1&M-2-mesoHAp. Samples
SBET (m2 g−1 )
Vp (cm3 g−1 )
Dp (nm)
S1 S2 S3
23.1 32.9 94.8
0.1 0.21 0.36
27 5.5 4.7 and 10
Additionally, the spectrum of S2 was similar to S3, demonstrating that the adding of TMB did not affect the formation of pure HAp. 3.3. Morphology observation
Fig. 1. (A) Wide-angle and (B) small-angle XRD patterns for the three samples: (S1) nHAp, (S2) M-1-mesoHAp and (S3) M-1&M-2-mesoHAp.
The morphologies of the three groups of nanoHAp samples were illustrated by SEM micrographs. As exhibited in Fig. 3, similar elliptical nanorods were obtained in all of the three groups, except the little changes in aspect ratios. The length of the nanoparticles was decreased from 100–200 nm (S1) to 50–150 nm (S3). The aspect ratio of S3 was lower than S1 and S2 slightly. The internal topography and mesoporous structure of the three samples was revealed by TEM micrographs. For S1 (Fig. 3S1-b), no mesoporous pore was obtained. For S2 (Fig. 3S2-b), numerous individual mesoporous (2–5 nm, white nanodots) was found obviously. By contrast, S3 (Fig. 3S3-b) possessed abundant enlarged mesoporous (5–10 nm) spread around the surfaces of HAp nanorods, demonstrating the pore-expanding of TMB. Furthermore, the subtle structure observed by high resolution TEM (HRTEM) demonstrated the open-ended mesoporous pore of S3 (Fig. 4A and B), and the maximum aperture was up to 15 nm (perhaps even more). Moreover, the representative hexagonal crystal of HAp was displayed clearly in Fig. 4C, as well as some penetrating cylindrical pores through the HAp nanorods. High magnification micrograph of HAp nanocrystals in Fig. 4D exhibited lattice fringes separations of 0.28 and 0.27 nm which correspond to the (2 1 0) and (0 0 2) planes of hexagonal HAp reflections, respectively. The HRTEM images of the nanorods further confirmed that the wellcrystallized single crystals of the mesoHAp nanorods. 3.4. Nitrogen adsorption isotherm The dimensions of mesoHAp were further confirmed via gas sorption isotherm (Fig. 5). Each nitrogen adsorption/desorption isotherm of the HAp samples can be categorized as type IV, with a distinct hysteresis loop. The BET surface area was calculated to be 23.1 m2 g−1 for S1, 32.9 m2 g−1 for S2, and 94.8 m2 g−1 for S3 (at 300 ◦ C). The typical H1 hysteresis loop of the S2 and S3 samples (Fig. 6A S2 and S3) indicated that there were a great amount of open-ended pores inside the HAp nanoparticles, which supported the TEM results well (Figs. 3 and 4). Combined with the TEM images, the BJH pore size distribution of S1 at 27 nm might attribute to the stacking pores of HAp nanoparticles. The obtained S2 sample had a narrow pore size distribution centered at 5.5 nm, indicating that the mesoporous dimension of mesoHAp was fabricated by CTAB micelles. Interesting, S3 exhibited a pore size distribution (Fig. 5D) with double peaks centered at 4.7 nm and 10 nm, which might be fabricated by two sizes micelles, mainly CTAB micelles and TMB swelled TMB/CTAB micelles. The pore volume was evaluated as 0.1 cm3 g−1 for S1, 0.21 cm3 g−1 for S2 and 0.36 cm3 g−1 for S3 (Table 1). 4. Discussion
Fig. 2. FTIR patterns for the three samples: (S1) nHAp, (S2) M-1-mesoHAp and (S3) M-1&M-2-mesoHAp, respectively.
In this work, the pore size of mesoHAp nanoparticles were successfully enlarged by using TMB as pore expanding agent and CTAB as template to structure micelle. The physicochemical properties of
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the synthesized HAp powders from different route (with or without expander and surfactant) have also been studied as control. The small-XRD study confirmed that the mesoHAp had abundant irregular mesoporous [26], which were very supported from TEM and BET. Obviously augmented specific surface area, pore volume and pore size were achieved through combination of CTAB and TMB. These results strongly implied that the role of pore expanding of TMB. On the basis of the results obtained, a hypothesized mechanism of pore expanding during the soft templating process was described as follow (as shown in Fig. 6). After vigorously stirring and ultrasonication, due to the high concentration, CTAB started to form spherical micelles by self-assembly in solution 1 (the CTAB micelle was denoted as M-1). And then PO4 3− species combined with CTAB micelles to construct CTA+ -PO4 3− complex micelles to balance cationic hydrophilic surfaces of the micelles. After sequent introduction of Ca2+ , Ca2+ combined on the surface of CTA+ -PO4 3− complex micelles immediately driven by the electrostatic interaction of PO4 3− . And then, Ca9 (PO4 )6 clusters were preferentially generated on the surface of complex micelles. Once a HAp crystal nucleus is established, subsequent abundant of HAp ordered arrays were formed automatically. The mesoHAp (S2) fabricated by CTAB micelles as soft template was formed in this route. Since the hydrophobic TMB can enter amphiphilic CTAB and solubilize in the micelles core of CTAB, the micelles can be dilatated
through solubilization of TMB. Followed by the sequently formation of CTA+ -PO4 3− micelles rapidly, the swelling complex micelles containing solubilized TMB droplet were in the majority (the TMB/CTAB micelle was denoted as M-2). Due to the swelling effect of TMB, the diameter size of M-2 was enlarged when compared with M-1, and then expanding the mesoporous pore size of HAp in the subsequent process. Nevertheless, notable that not all TMB dissolved into the CTAB micelles, thus some pure CTAB micelles were concurrence exited in the system. Interesting, bifarous pore size distributions centered at ∼4.7 nm and ∼10 nm were existed in the as-synthesized mesoHAp (as shown in Fig. 5D), which might be attributed to the coexist of pure CTAB micelles (M-1) and solubilized TMB/CTAB micelles (M-2), and formed mainly two kinds of mesoporous poses size during the process. After template removing and calcination, very broad pore size distributions (from 4 nm to 15 nm, or perhaps even larger) of S3 was clearly observed in Figs. 3 and 4 TEM images. Once an ordered HAp array was established, subsequent thermal processing was used to remove the templates and produce a stable mesoporous structure HAp. The templates consisted of TMB and CTAB can then be easily removed by water and ethanol solution after the high temperature refluxing. Followed by calcination, the residual TMB and CTAB molecules were removed, and the mesoporous pores in the HAp nanorods were obtained.
Fig. 3. SEM and TEM images for the three samples: (S1) nHAp, (S2) M-1-mesoHAp and (S3) M-1&M-2-mesoHAp.
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Fig. 4. HRTEM micrographs of HAp powders (S3): (A) from the morphology, (B) from the structure and pore diameter, (C) from the hexagonal structure of HAp nanorod and (D) the nanocrystal structure.
Fig. 5. (A) Nitrogen adsorption/desorption isotherm of (S1) nHAp, (S2) M-1-mesoHAp and (S3) M-1&M-2-mesoHAp, (B) BJH pore size distribution for S1 (nHAp), (C) BJH pore size distribution for S2 (M-1-mesoHAp) and (D) BJH pore size distribution for S3 (M-1&M-2-mesoHAp).
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Fig. 6. The possible mechanism of the pore size expanding of mesoporous HAp via adding TMB as pore expanding agent.
In comparison with hard template and polymeric surfactant template methods, the lager pore size mesoHAp can be obtained under facile condition and simple route with low cost. In particular, the synthesized pore-expanded mesoHAp might possess potential applications in drug delivery systems and/or bone tissue engineering [16,17,31]. Nevertheless, the microtacticity the as-synthesized mesoHAp should be improved. So further optimization for control the pore size was still needed, particularly for obtain uniform and regular pore size mesoHAp nanoparticles. 5. Conclusions In the present work, we successfully enlarged the pore size of mesoporous HAp nanoparticles through a modified soft-templating route, which TMB was used as pore expanding agent and CTAB used as template to structure micelles. TEM images demonstrated numerous channels spreading and penetrating within the nanorods, as well as the obviously enlarged channel dimensions ranging from 5 to 10 nm, and the maximum pore size was up to 15 nm. Incremental pore size, surface area and pore volume were obtained according to the N2 adsorption–desorption data, confirming the chambering effect of TMB. The mesoHAp nanoparticles with large nanoscale pore size presented a platform for drug delivery system and might be applicable in bone regeneration. Acknowledgments The authors are indebted to the financial support from the National Basic Research Program of China (973 Program, 2012CB933600), the National Natural Science Foundation of China (No. 31271011), the National Science and Technology Support Program (2012BAI17B02), and the Program for New Century Excellent Talents in University (NCET-12-0856). References [1] C. Agrawal, R.B. Ray, Biodegradable polymeric scaffolds for musculoskeletal tissue engineering, J. Biomed. Mater. Res. 55 (2001) 141–150. [2] D.M. Antonelli, J.Y. Ying, Synthesis of a stable hexagonally packed mesoporous niobium oxide molecular sieve through a novel ligand-assisted templating mechanism, Angew. Chem. Int. Ed. Engl. 35 (1996) 426–430. [3] A. Dong, N. Ren, Y. Tang, Y. Wang, Y. Zhang, W. Hua, et al., General synthesis of mesoporous spheres of metal oxides and phosphates, J. Am. Chem. Soc. 125 (2003) 4976–4977.
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Contents lists available at ScienceDirect
Colloids and Surfaces A: Physicochemical and Engineering Aspects journal homepage: www.elsevier.com/locate/colsurfa
Preparation of pore expanded mesoporous hydroxyapatite via auxiliary solubilizing template method Fanyan Zeng c , Jing Wang c,∗ , Yi Wu c , Yuanman Yu c , Wei Tang c , Manli Yin c , Changsheng Liu a,b,c,∗∗ a
The State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai 200237, PR China Key Laboratory for Ultrafine Materials of Ministry of Education, East China University of Science and Technology, Shanghai 200237, PR China c Engineering Research Center for Biomedical Materials of Ministry of Education, East China University of Science and Technology, Shanghai 200237, PR China b
h i g h l i g h t s
g r a p h i c a l
a b s t r a c t
• CTAB and TMB were used as soft • • • •
template and pore expanding agent, respectively. Average length of the as-synthesized HAp nanoparticles is 50–150 nm. Large amount of mesoporous spread around the surface of mesoHAp nanorods. The shape of mesopores was elongated and opened at both extremities. Pore diameter of mesoHAp was up to 15 nm, indicating the pore enlargement of TMB.
a r t i c l e
i n f o
Article history: Received 23 April 2013 Received in revised form 7 September 2013 Accepted 1 October 2013 Available online 16 October 2013 Keywords: Mesoporous materials Hydroxyapatite Soft-tempalte Pore expanding agent Micelles
a b s t r a c t Here we present a facile approach to prepare pore-expanding mesoporous hydroxyapatite (mesoHAp) using solubilized micelle template. 1,3,5-rimethy benzene (TMB) was selected as auxiliary solubilizer together with the general soft template cetyltrimethylammonium bromide (CTAB). Enlarged mesoporous can be obtained through the swelling of micelle. Numerous individual nano channels can be observed under TEM images spreading and penetrating within the mesoHAp nanorods. Compared to the mesoHAp without TMB, the channels have enlarged dimensions of about 5–15 nm and the space between the nano channels are filled with an ordered crystalline HAp structure with typical hexagonal crystals. A probable mechanism is that TMB can enter into the amphiphilic CTAB micelle to form swelled TMB/CTAB-PO4 3− complex, and in the presence of Ca2+ , Ca9 (PO4 )6 clusters are preferentially condensed on the micelle surface due to the conformation compatibility between the identical hexagonal shapes of the micelles and Ca9 (PO4 )6 . Interesting, the pore size distribution of mesoHAp was centered at ∼4.7 nm and ∼10 nm, which might be arisen from the coexistence of both unsolubilized CTAB micelles and solubilized TMB/CTAB micelles. The pore-enlarged mesoHAp nanoparticles presented a platform for protein delivery system and might be applicable in biocomposite scaffold for bone regeneration. © 2013 Elsevier B.V. All rights reserved.
1. Introduction ∗ Corresponding author. ∗∗ Corresponding author at: Engineering Research Center for Biomedical Materials of Ministry of Education, East China University of Science and Technology, Shanghai 200237, PR China. E-mail addresses: [email protected] (F. Zeng), [email protected] (J. Wang), [email protected] (C. Liu). 0927-7757/$ – see front matter © 2013 Elsevier B.V. All rights reserved. http://dx.doi.org/10.1016/j.colsurfa.2013.10.028
Recently, the synthesis of inorganic mesoporous materials has attracted much attention in chemistry and materials communities because of their low density, large specific area and pore volume, small size, mechanical and thermal stabilities, and surface permeability [1–3]. Up to now, a variety of mesoporous materials have
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been developed including the representative mesoporous silicabased molecular sieves, such as SBA and MCM. As one of the most energetic research areas in materials science [4], mesoporous silicabased nanoparticles (MSNs) have variety of potential applications in cosmetic, catalysis, coatings, composite materials, dyes, ink, artificial cells and fillers [5–8], etc. Despite the hot topic, silica-based mesoporous materials may not be suitable for tissue regeneration in vivo since its vague biological response. Hydroxyapatite (Ca10 (PO4 )6 (OH)2 , HAp), the major inorganic component of bone and teeth, is a key biomaterial in potential orthopedic [9], dental, and maxillofacial therapies because of the excellent biocompatibility, bioactivity, and osteoconductivity [10–13]. Moreover, it is worth noting that mesoporous HAp (mesoHAp) nanoparticles have greater potential in drug delivery systems, due to the distinct advantages of highly ordered mesoporous structure, large surface area and porosity that provide excellent loading capacity and releasing profile. Therefore, mesoHAp can be incorporated into scaffolds for the beneficial effects of improving osteogenesis and delivery of biologically active molecules [14]. However, despite their favorable properties, fabrication of mesoHAp with higher surface area is difficulty owing to its preferable crystallization in aqueous solution and then cannot interact with surfactant molecules. According to the literature, most of mesoporous calcium phosphate has the surface areas of 20–60 m2 g−1 . Another challenge lies in the relative smaller pore diameters less than 5 nm [15], whereas most cytokines are 8 nm or larger [16–18]. Therefore, a number of studies have been focused on the improvement of the pore diameter of mesoHAp [16,19,20]. Various techniques have been utilized to fabricate mesoHAp, including sol–gel method [19], hydrothermal method [16], microemulsion process [20] and co-precipitation technique [21], there into the templating method is regarded as the most valid approach to obtain mosoHAp. A series of surfactants, including pluronic P123 [22,23], sodium dodecyl sulfate (SDS) [24], non-ionic block co-polymer pluronic F127 [25,26] and cetyltrimethylammonium bromide (CTAB) [15,27], have been used as templates for synthesis of mesoporous materials. For example, Coelho et al. [27] synthesized HAp nanorods using CTAB and the effect of the sintering temperature on its nanostructure was studied. Li et al. [15] synthesized HAp using CTAB and studied the impact of reaction temperature and CTAB/PO4 3− ratio on its thermostability. However, most of these studies are focus on the improvement of stability of HAp, the efficient strategy of mesoporous pore size enlargement is still defective. Therefore, synthesis of large pore size mesoHAp is an extremely promising research. In recent research of ordered mesoporous siliceous materials, additional organic molecules have been appended to the template to achieve pore-expanding [28]. Inspired by this method, an alkylated benzene hydrocarbons, 1,3,5-trimethy benzene (TMB) is involved combined with the general soft template CTAB. The auxiliary TMB is conductive to the enlargement of pore diameter of mesoHAp through the micellar solubilization. The physicochemical properties are investigated, and the possible mechanism of pore size expanding is proposed.
to adjust the pH to 12). Then, 4.44 g of CaCl2 was directly added into 60 mL H2 O to form solution 2. After vigorously stirring and ultrasonication respectively until optically transparent, solution 2 was introduced into the well-dispersed solution 1drop by drop. The reactant molar ratio of Ca2+ /PO4 3− was kept at 1.67. After additional agitation at ambient temperature and normal atmospheric pressure for 3 h, the as-obtained mixing solution was refluxed at 120 ◦ C for 48 h to remove the template of CTAB and TMB, followed by cooling to room temperature naturally. Finally, the precipitate was separated by centrifugation and washing with deionized water and ethanol for six times repeatedly, and dried in vacuum at 60 ◦ C for 24 h, then calcined in a furnace at 550 ◦ C for 6 h to obtain the final mesoHAp (denote as S3). The samples synthesized without TMB (denote as S2) and without template (nHAp, denote as S1) were used as control. 2.2. Characterization The wide-angle ( from 10 to 100◦ ) and small-angle ( from 0 to 5◦ ) XRD patterns were recorded by using a SHIMADZU model XRD6000 X-ray powder diffractometer (Cu K␣ radiation, 40 kV, 30 mA and a scanning speed 2.08 (2)/min). Fourier transform infra-red (FTIR) spectrum was collected on a FTIT-AVATAR370 spectrophotometer over the range of wavenumber 4000–300 cm−1 using KBr pellet. Morphologies were examined via a field-emission-type scanning electron microscope (FSEM, SIRION-100). Transmission electron microscope (TEM) images were obtained on a JEOL-2010 Electron Microscope with an acceleration voltage of 120 kV N2 adsorption/desorption analysis was performed at 77 K using a Quantachrome Quadrasorb SI apparatus. The specific surface area was determined by the Bruaauer–Emmett–Teller (BET) method, the pore parameters (pore volume and pore diameter) were evaluated from the desorption branch of isotherm based on Barrett–Joyner–Halenda (BJH) model.
3. Results 3.1. X-ray diffractions The wide-angle XRD patterns of the obtained samples (S1, S2 and S3) were shown in Fig. 1A. All the diffraction peaks of the three samples corresponded to the standard characteristic peaks of HAp (JCPDS card: No. 24-0033), indicating that the phase of the samples was highly pure HAp. Small-angle (2 < 5◦ ) XRD diffraction was used to verify the existence of long-range ordered structure inside the samples [26]. As shown in Fig. 1B, S1 exhibited a smooth curve compared to S2 and S3. However, numerous peaks and background appeared in the XRD pattern of S2 and S3, especially from 2 to 4◦ , indicating irregular mesoporous structures existed in S2 and S3. Furthermore, no significant difference was observed between S2 and S3 from Fig. 1B. 3.2. FT-IR spectroscopy
2. Experimental 2.1. Materials and synthesis procedure The procedure employed for the synthesis of HAp nanorods was as follows and all reagents were of analytical grade, purchased from Shanghai Chemical Co., Ltd., PR China and used with no further purification. In a typical procedure, 5.48 g of K2 HPO4 ·3H2 O, 8.74 g of CTAB, and 2.88 g of TMB were dispensed in deionized water to form 100 mL solution 1 (1 M sodium hydroxide solution was used
Fig. 2 shows the FTIR spectra of the three samples. For S3, phosphate absorption bands occurred at 474, 563, 964, 1032 and 1092 cm−1 , and the hydroxyl absorption bands at 3572 and 634 cm−1 were characteristic of a typical characteristic absorptions of hydroxyapatite [29]. The peaks at 3433 and 1639 cm−1 were assigned to the bending mode of the adsorbed water [30]. The two sharp and weak peaks at 721, 2854 and 2924 cm−1 were attributed to the residual of CTAB [17]. No trace of TMB was observed from the FTIR spectra, indicating TMB was removed cleanly after the high temperature refluxing, repeated washing and calcining.
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Table 1 The textural parameters of samples analyzed with nitrogen adsorption–desorption method: (S1) nHAp, (S2) M-1-mesoHAp and (S3) M-1&M-2-mesoHAp. Samples
SBET (m2 g−1 )
Vp (cm3 g−1 )
Dp (nm)
S1 S2 S3
23.1 32.9 94.8
0.1 0.21 0.36
27 5.5 4.7 and 10
Additionally, the spectrum of S2 was similar to S3, demonstrating that the adding of TMB did not affect the formation of pure HAp. 3.3. Morphology observation
Fig. 1. (A) Wide-angle and (B) small-angle XRD patterns for the three samples: (S1) nHAp, (S2) M-1-mesoHAp and (S3) M-1&M-2-mesoHAp.
The morphologies of the three groups of nanoHAp samples were illustrated by SEM micrographs. As exhibited in Fig. 3, similar elliptical nanorods were obtained in all of the three groups, except the little changes in aspect ratios. The length of the nanoparticles was decreased from 100–200 nm (S1) to 50–150 nm (S3). The aspect ratio of S3 was lower than S1 and S2 slightly. The internal topography and mesoporous structure of the three samples was revealed by TEM micrographs. For S1 (Fig. 3S1-b), no mesoporous pore was obtained. For S2 (Fig. 3S2-b), numerous individual mesoporous (2–5 nm, white nanodots) was found obviously. By contrast, S3 (Fig. 3S3-b) possessed abundant enlarged mesoporous (5–10 nm) spread around the surfaces of HAp nanorods, demonstrating the pore-expanding of TMB. Furthermore, the subtle structure observed by high resolution TEM (HRTEM) demonstrated the open-ended mesoporous pore of S3 (Fig. 4A and B), and the maximum aperture was up to 15 nm (perhaps even more). Moreover, the representative hexagonal crystal of HAp was displayed clearly in Fig. 4C, as well as some penetrating cylindrical pores through the HAp nanorods. High magnification micrograph of HAp nanocrystals in Fig. 4D exhibited lattice fringes separations of 0.28 and 0.27 nm which correspond to the (2 1 0) and (0 0 2) planes of hexagonal HAp reflections, respectively. The HRTEM images of the nanorods further confirmed that the wellcrystallized single crystals of the mesoHAp nanorods. 3.4. Nitrogen adsorption isotherm The dimensions of mesoHAp were further confirmed via gas sorption isotherm (Fig. 5). Each nitrogen adsorption/desorption isotherm of the HAp samples can be categorized as type IV, with a distinct hysteresis loop. The BET surface area was calculated to be 23.1 m2 g−1 for S1, 32.9 m2 g−1 for S2, and 94.8 m2 g−1 for S3 (at 300 ◦ C). The typical H1 hysteresis loop of the S2 and S3 samples (Fig. 6A S2 and S3) indicated that there were a great amount of open-ended pores inside the HAp nanoparticles, which supported the TEM results well (Figs. 3 and 4). Combined with the TEM images, the BJH pore size distribution of S1 at 27 nm might attribute to the stacking pores of HAp nanoparticles. The obtained S2 sample had a narrow pore size distribution centered at 5.5 nm, indicating that the mesoporous dimension of mesoHAp was fabricated by CTAB micelles. Interesting, S3 exhibited a pore size distribution (Fig. 5D) with double peaks centered at 4.7 nm and 10 nm, which might be fabricated by two sizes micelles, mainly CTAB micelles and TMB swelled TMB/CTAB micelles. The pore volume was evaluated as 0.1 cm3 g−1 for S1, 0.21 cm3 g−1 for S2 and 0.36 cm3 g−1 for S3 (Table 1). 4. Discussion
Fig. 2. FTIR patterns for the three samples: (S1) nHAp, (S2) M-1-mesoHAp and (S3) M-1&M-2-mesoHAp, respectively.
In this work, the pore size of mesoHAp nanoparticles were successfully enlarged by using TMB as pore expanding agent and CTAB as template to structure micelle. The physicochemical properties of
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the synthesized HAp powders from different route (with or without expander and surfactant) have also been studied as control. The small-XRD study confirmed that the mesoHAp had abundant irregular mesoporous [26], which were very supported from TEM and BET. Obviously augmented specific surface area, pore volume and pore size were achieved through combination of CTAB and TMB. These results strongly implied that the role of pore expanding of TMB. On the basis of the results obtained, a hypothesized mechanism of pore expanding during the soft templating process was described as follow (as shown in Fig. 6). After vigorously stirring and ultrasonication, due to the high concentration, CTAB started to form spherical micelles by self-assembly in solution 1 (the CTAB micelle was denoted as M-1). And then PO4 3− species combined with CTAB micelles to construct CTA+ -PO4 3− complex micelles to balance cationic hydrophilic surfaces of the micelles. After sequent introduction of Ca2+ , Ca2+ combined on the surface of CTA+ -PO4 3− complex micelles immediately driven by the electrostatic interaction of PO4 3− . And then, Ca9 (PO4 )6 clusters were preferentially generated on the surface of complex micelles. Once a HAp crystal nucleus is established, subsequent abundant of HAp ordered arrays were formed automatically. The mesoHAp (S2) fabricated by CTAB micelles as soft template was formed in this route. Since the hydrophobic TMB can enter amphiphilic CTAB and solubilize in the micelles core of CTAB, the micelles can be dilatated
through solubilization of TMB. Followed by the sequently formation of CTA+ -PO4 3− micelles rapidly, the swelling complex micelles containing solubilized TMB droplet were in the majority (the TMB/CTAB micelle was denoted as M-2). Due to the swelling effect of TMB, the diameter size of M-2 was enlarged when compared with M-1, and then expanding the mesoporous pore size of HAp in the subsequent process. Nevertheless, notable that not all TMB dissolved into the CTAB micelles, thus some pure CTAB micelles were concurrence exited in the system. Interesting, bifarous pore size distributions centered at ∼4.7 nm and ∼10 nm were existed in the as-synthesized mesoHAp (as shown in Fig. 5D), which might be attributed to the coexist of pure CTAB micelles (M-1) and solubilized TMB/CTAB micelles (M-2), and formed mainly two kinds of mesoporous poses size during the process. After template removing and calcination, very broad pore size distributions (from 4 nm to 15 nm, or perhaps even larger) of S3 was clearly observed in Figs. 3 and 4 TEM images. Once an ordered HAp array was established, subsequent thermal processing was used to remove the templates and produce a stable mesoporous structure HAp. The templates consisted of TMB and CTAB can then be easily removed by water and ethanol solution after the high temperature refluxing. Followed by calcination, the residual TMB and CTAB molecules were removed, and the mesoporous pores in the HAp nanorods were obtained.
Fig. 3. SEM and TEM images for the three samples: (S1) nHAp, (S2) M-1-mesoHAp and (S3) M-1&M-2-mesoHAp.
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Fig. 4. HRTEM micrographs of HAp powders (S3): (A) from the morphology, (B) from the structure and pore diameter, (C) from the hexagonal structure of HAp nanorod and (D) the nanocrystal structure.
Fig. 5. (A) Nitrogen adsorption/desorption isotherm of (S1) nHAp, (S2) M-1-mesoHAp and (S3) M-1&M-2-mesoHAp, (B) BJH pore size distribution for S1 (nHAp), (C) BJH pore size distribution for S2 (M-1-mesoHAp) and (D) BJH pore size distribution for S3 (M-1&M-2-mesoHAp).
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Fig. 6. The possible mechanism of the pore size expanding of mesoporous HAp via adding TMB as pore expanding agent.
In comparison with hard template and polymeric surfactant template methods, the lager pore size mesoHAp can be obtained under facile condition and simple route with low cost. In particular, the synthesized pore-expanded mesoHAp might possess potential applications in drug delivery systems and/or bone tissue engineering [16,17,31]. Nevertheless, the microtacticity the as-synthesized mesoHAp should be improved. So further optimization for control the pore size was still needed, particularly for obtain uniform and regular pore size mesoHAp nanoparticles. 5. Conclusions In the present work, we successfully enlarged the pore size of mesoporous HAp nanoparticles through a modified soft-templating route, which TMB was used as pore expanding agent and CTAB used as template to structure micelles. TEM images demonstrated numerous channels spreading and penetrating within the nanorods, as well as the obviously enlarged channel dimensions ranging from 5 to 10 nm, and the maximum pore size was up to 15 nm. Incremental pore size, surface area and pore volume were obtained according to the N2 adsorption–desorption data, confirming the chambering effect of TMB. The mesoHAp nanoparticles with large nanoscale pore size presented a platform for drug delivery system and might be applicable in bone regeneration. Acknowledgments The authors are indebted to the financial support from the National Basic Research Program of China (973 Program, 2012CB933600), the National Natural Science Foundation of China (No. 31271011), the National Science and Technology Support Program (2012BAI17B02), and the Program for New Century Excellent Talents in University (NCET-12-0856). References [1] C. Agrawal, R.B. Ray, Biodegradable polymeric scaffolds for musculoskeletal tissue engineering, J. Biomed. Mater. Res. 55 (2001) 141–150. [2] D.M. Antonelli, J.Y. Ying, Synthesis of a stable hexagonally packed mesoporous niobium oxide molecular sieve through a novel ligand-assisted templating mechanism, Angew. Chem. Int. Ed. Engl. 35 (1996) 426–430. [3] A. Dong, N. Ren, Y. Tang, Y. Wang, Y. Zhang, W. Hua, et al., General synthesis of mesoporous spheres of metal oxides and phosphates, J. Am. Chem. Soc. 125 (2003) 4976–4977.
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