- Email: [email protected]
Constructing 3D scaffold with 40-nm-diameter hollow mesoporous bioactive glass nanofibers
Materials Letters 248 (2019) 201–203
Contents lists available at ScienceDirect
Materials Letters journal homepage: www.elsevier.com/locate/mlblue
Constructing 3D scaffold with 40-nm-diameter hollow mesoporous bioactive glass nanofibers Jian Xiao a, Yizao Wan a,b, Fanglian Yao c, Yuan Huang a, Yong Zhu c, Zhiwei Yang a,b,⇑, Honglin Luo a,b,⇑ a
School of Materials Science and Engineering, Tianjin University, Tianjin 300072, China Institute of Advanced Materials, School of Materials Science and Engineering, East China Jiaotong University, Nanchang 330013, China c Key Laboratory of Systems Bioengineering of Ministry of Education, School of Chemical Engineering and Technology, Tianjin University, Tianjin 300072, China b
a r t i c l e
i n f o
Article history: Received 20 February 2019 Received in revised form 5 April 2019 Accepted 10 April 2019 Available online 10 April 2019 Keywords: Sol–gel preparation Biomaterials Bioactive glass Nanotube Mesoporous structure Scaffold
a b s t r a c t In this paper, a novel three-dimensional (3D) scaffold consisting of hollow mesoporous bioactive glass (MBG) nanofibers was synthesized via template-assisted sol–gel method. The hollow mesoporous fibers show an ultra-small diameter of around 40 nm, which is the smallest among all currently reported MBG fibers, and the resultant scaffold possesses a large specific surface area of 579.0 m2 g 1, which is the largest of all MBG products reported so far. It is believed that such ultrafine diameter and the presence of mesopores will endow the scaffold with excellent bioactivity, which makes it a promising candidate in controlled drug release and bone tissue engineering. Ó 2019 Elsevier B.V. All rights reserved.
1. Introduction Bioactive glasses (BGs) play a central role in bone regeneration due to their excellent in vitro bioactivity, osteoconductivity and osteoinductivity [1]. Recently, nanofibrous BG scaffolds have gained much interest since their structural resemblance to extracellular matrix (ECM) enables them to manipulate cell fate by providing topographical cues [2,3]. The nanofibrous BG structure provides high specific surface area which allows for rapid dissolution of ions, high protein absorption [4], controlled drug delivery [5] and osteogenic potential [4]. Accordingly, much effort has been devoted to increasing specific surface area of BG fibrous scaffolds. To date, there are two effective ways of achieving this. The first method is to induce porosity and hollowness [6,7]. The second strategy is to reduce the diameter of BG fibers. Although MBG scaffolds with small fibers can offer large surface area, the current technologies (mostly based on electrospinning) are unable to produce ultrafine BG fibers smaller than 100 nm. No report can be found in literature on hollow MBG fibers (namely nanotubes) with a diameter of less than 50 nm. ⇑ Corresponding authors at: Institute of Advanced Materials, School of Materials Science and Engineering, East China Jiaotong University, Nanchang 330013, China. E-mail addresses: [email protected] (Z. Yang), [email protected] (H. Luo). https://doi.org/10.1016/j.matlet.2019.04.041 0167-577X/Ó 2019 Elsevier B.V. All rights reserved.
In this work, we report a novel three-dimensional (3D) scaffold composed of hollow ultrafine MBG fibers (ca. 40 nm) via a facile and scalable template-assisted sol–gel method. The effects of processing variables such as ethanol to water ratio (Ve:Vw), aging time (t) and calcination temperature (T) on the structure of the scaffolds were investigated. 2. Experimental 2.1. Preparation of MBGH scaffold The hollow MBG fiber (MBGH) scaffold was prepared by template-assisted sol–gel method using bacterial cellulose (BC) and nonionic block copolymer (P123) as co-templates. In a typical process, 4 g of P123 was dissolved in 50 mL of ethanol, then 9 mL of tetraethyl orthosilicate (TEOS), 1.75 g of Ca(NO3)24H2O (CN) and 0.85 mL of triethyl phosphate (TEP) were added into the solution and stirred for 24 h. Subsequently, 125 mg of BC was immersed in the solution. After stirring for another 24 h, the obtained materials were rinsed with ethanol and then soaked in the mixture of ethanol and water with varying ratios (Ve:Vw = 6:1, 9:1 and 12:1) for 12, 24 and 36 h to undergo hydrolysis and poly-condensation. Finally, specimens were freeze-dried and calcined at 500, 600 and 700 °C for 5 h.
202
J. Xiao et al. / Materials Letters 248 (2019) 201–203
2.2. Characterizations To determine whether nanotubular structure was obtained, products were observed using transmission electron microscopy (TEM, Tecnai G2F-20) and the obtained MBGH scaffold was further characterized by scanning electron microscopy (SEM, Hitachi S4800). Energy dispersive X-ray spectroscopy (EDS) was used to qualitatively analyze the surface chemical composition of the scaffold. In addition, X-ray diffraction (XRD, Rigaku D/Max 2500 v/pc) and N2 adsorption–desorption analyses (Quantachrome NOVA 2200e) were carried out.
3. Results and discussion In the present study, we investigated the effects of processing variables including Ve:Vw, t and T on the structure of the resultant products. We find that Ve:Vw = 9:1 is the optimum value to obtain nanotubular structure (Fig. 1b), otherwise the resultants are nanofibers (Fig. 1a) and nanoparticles (Fig. 1c) when Ve:Vw = 6:1 and 12:1, respectively, due to the fact that too fast or too slow hydrolysis rate results in uncontrollable synthesis process, not favorable to obtain nanotubular structure. The aging time also has a significant impact on product structure. At t = 24 h, a typical nanotube can be obtained (Fig. 1b) while t = 12 and 36 h results in nanofibers (Fig. 1d) and nanoparticles (Fig. 1e), respectively. The results indicate that too short or too long aging time is also not favorable to obtain nanotubular structure. Similarly, nanotubular products can be obtained when T = 600 °C while nanoparticles (Fig. 1f and g) are noted at T = 500 and 700 °C. The high calcination temperature causes overheating, which can result in structural collapse, only forming the nanoparticles. Similarly, it is also difficult to create nanotubular structure at the low calcination temperature. As shown in Fig. 1h, under optimum parameters (Ve:Vw = 9:1, t = 24 h and T = 600 °C), a sound nanotubular scaffold can be obtained which almost fully inherits the 3D interconnected porous structure of BC (Fig. 1i). The resultant nanotubes show a diameter of around 40 nm and a wall thickness of 8 nm (Fig. 1b). The typical
Fig. 2. Typical fabrication process of MBGH scaffold.
fabrication process of MBGH scaffold is schematically illustrated in Fig. 2. The hydroxyl groups on the surface of BC fibers may also act as a catalyst to accelerate the hydrolysis and condensation of the precursors, thus promoting the formation of MBGH. As shown in Fig. 3a, EDS results confirm the presence of Si, Ca, P and O in MBGH scaffold. The wide-angle XRD pattern reveals the amorphous nature of MBGH scaffold since no diffraction peak is noted except for a wide SiO2 peak at 2h = 25° (Fig. 3b) [8]. The small-angle XRD pattern demonstrates an apparent diffraction peak at 2h = 0.5–1° (inset in Fig. 3b), suggesting that there are ordered mesopores in MBGH scaffold [9]. The high-resolution TEM (HRTEM) further confirms presence of mesopores (3.8 nm) in nanotube walls (Fig. 3c). Moreover, N2 adsorption–desorption result verifies typical IV isotherms and shows hysteresis loop (Fig. 3d), which is an indication of mesoporous structure, agreeing with the previous reports [10,11]. Fig. 3d suggests that MBGH scaffold possesses dual mesopore sizes of 3.9 and 15.1 nm, the former being pores in the walls and the latter being formed by neighboring nanotubes. N2 adsorption–desorption measurement reveals a large surface area of 579.0 m2 g 1. The pore size (3.9 nm) in tube walls is comparable to that of previously reported MBG powder [12] and thick MBG fibers [1] while the surface area is significantly larger than all MBG products reported so far (Table 1) [1,7,13–18], which is due to its ultra-small tube diameter than literature values (Table 1) [7,14–19]. The presence of mesopores and large surface area can significantly improve its bioactivity [20]. In addition, the bioactive agents (such as drugs and growth factors) can be incorporated into MBGH scaffold through mesopores (for small molecular drugs) [21] and the cavities of nanotubes (for big molecular growth factors). Therefore, such MBGH scaffold holds great promise in tissue engineering and regenerative medicine as well as drug delivery.
4. Conclusions
Fig. 1. (a–g) TEM images of various products prepared under different conditions. (h) SEM of MBGH prepared at optimum conditions (Ve:Vw = 9:1, t = 24 h and T = 600 °C). (i) SEM image of BC (inset shows low magnified TEM image in Fig. 1b).
We have successfully prepared a novel 3D scaffold consisting of hollow ultrafine MBG fibers (namely nanotubes) using templateassisted sol–gel method. There are ordered mesopores in the tube walls with a size of 3.9 nm. The nanotubes have an ultra-small diameter of ca. 40 nm which is the smallest among all reported values and the MBGH scaffold shows a larger specific surface area (579.0 m2 g 1) than all MBG reported so far. It is expected that the hollowness and fine fibers enable the scaffold to exhibit good
203
J. Xiao et al. / Materials Letters 248 (2019) 201–203
Fig. 3. (a) EDS elemental mapping, (b) wide-angle XRD pattern (inset shows small-angle XRD pattern), (c) HRTEM image, and (d) N2 adsorption–desorption isotherms (inset presents the pore size distribution) of MBGH scaffold.
Table 1 Comparisons of fiber diameter, specific surface area and pore size of bioactive glass prepared by different methods. Method
Outer diameter (nm)
Inner diameter (nm)
Specific surface area (m2 g 1)
Pore size (nm)
Refs.
Electrospinning
400.0 450.0 330.0 500.0 300.0 45.0
200.0 280.0 170.0 100.0 160.0 25.0
154.0 449.7 – – 52.0 579.0
2.0–9.0 1.7 – – lm 3.9
[7] [14] [15] [16] [17] this work
Collagen-template BC template
bioactivity and sustainable drug delivery, which make it very promising in the applications of tissue engineering and drug delivery. Conflict of interest None. Acknowledgements This work was supported by the National Natural Science Foundation of China (Nos. 51572187 and 30660264) and the Youth Science Foundation of Jiangxi Province (Grant no. 20181BAB216010). References [1] F.-Y. Hsu, H.-W. Hsu, Y.-H. Chang, J.-L. Yu, L.-R. Rau, S.-W. Tsai, Mater. Sci. Eng. C 89 (2018) 346–354. [2] E. Schnell, K. Klinkhammer, S. Balzer, G. Brook, D. Klee, P. Dalton, J. Mey, Biomaterials 28 (2007) 3012–3025. [3] S. Chen, S.K. Boda, S.K. Batra, X. Li, J. Xie, Adv. Healthc. Mater. 7 (2018) 1701024–1701044.
[4] C. Gao, Q. Gao, X. Bao, Y. Li, A. Teramoto, K. Abe, J. Am. Ceram. Soc. 94 (2011) 2841–2845. [5] Y. Hong, X. Chen, X. Jing, H. Fan, B. Guo, Z. Gu, X. Zhang, Adv. Mater. 22 (2010) 754–758. [6] H. Lu, T. Zhang, X.P. Wang, Q.F. Fang, J. Mater. Sci.: Mater. Med. 20 (2009) 793– 798. [7] Y. Hong, X. Chen, X. Jing, H. Fan, Z. Gu, X. Zhang, Adv. Funct. Mater. 20 (2010) 1503–1510. [8] R.F.P. Pereira, K. Zehbe, C. Gunter, T. Dos Santos, S.C. Nunes, F.A.A. Paz, M.M. Silva, P.L. Granja, A. Taubert, V. de Zea Bermudez, ACS Omega 3 (2018) 10811– 10822. [9] N. Gomez-Cerezo, E. Verron, V. Montouillout, F. Fayon, P. Lagadec, J.M. Bouler, B. Bujoli, D. Arcos, M. Vallet-Regi, Acta Biomater. 76 (2018) 333–343. [10] X. Li, X. Chen, G. Miao, H. Liu, C. Mao, G. Yuan, Q. Liang, X. Shen, C. Ning, X. Fu, J. Mater. Chem. B 2 (2014) 7045–7054. [11] X. Li, F. Qu, W. Li, H. Lin, Y. Jin, J. Sol-Gel Sci. Technol. 63 (2012) 416–424. [12] C. Wu, J. Chang, Interface Focus 2 (2012) 292–306. [13] A. El-Fiqi, J.-H. Kim, H.-W. Kim, A.C.S. Appl, Mater. Interfaces 7 (2015) 1140– 1152. [14] Z. Ma, G. Dong, C. Lv, J. Qiu, Mater. Lett. 88 (2012) 136–139. [15] B. Song, L. Wu, C. Wu, J. Chang, Biomed. Glasses 1 (2015) 136–139. [16] J. Xie, E.R. Blough, C.H. Wang, Acta Biomater. 8 (2012) 811–819. [17] S. Chen, A. Osaka, N. Hanagata, J. Mater. Chem. 21 (2011) 4332–4338. [18] W. Liu, X. Wang, X. Gao, X. Chen, X. Yu, H. Wang, X. Deng, Ceram. Int. 39 (2013) 8521–8526. [19] N. Ghaebi Panah, P. Alizadeh, B. Eftekhari Yekta, N. Motakef-Kazemi, Ceram. Int. 42 (2016) 10935–10942. [20] Y. Zhang, L. Xia, D. Zhai, M. Shi, Y. Luo, C. Feng, B. Fang, J. Yin, J. Chang, C. Wu, Nanoscale 7 (2015) 19207–19221. [21] C. Wu, Y. Zhou, J. Chang, Y. Xiao, Acta Biomater. 9 (2013) 9159–9168.
Contents lists available at ScienceDirect
Materials Letters journal homepage: www.elsevier.com/locate/mlblue
Constructing 3D scaffold with 40-nm-diameter hollow mesoporous bioactive glass nanofibers Jian Xiao a, Yizao Wan a,b, Fanglian Yao c, Yuan Huang a, Yong Zhu c, Zhiwei Yang a,b,⇑, Honglin Luo a,b,⇑ a
School of Materials Science and Engineering, Tianjin University, Tianjin 300072, China Institute of Advanced Materials, School of Materials Science and Engineering, East China Jiaotong University, Nanchang 330013, China c Key Laboratory of Systems Bioengineering of Ministry of Education, School of Chemical Engineering and Technology, Tianjin University, Tianjin 300072, China b
a r t i c l e
i n f o
Article history: Received 20 February 2019 Received in revised form 5 April 2019 Accepted 10 April 2019 Available online 10 April 2019 Keywords: Sol–gel preparation Biomaterials Bioactive glass Nanotube Mesoporous structure Scaffold
a b s t r a c t In this paper, a novel three-dimensional (3D) scaffold consisting of hollow mesoporous bioactive glass (MBG) nanofibers was synthesized via template-assisted sol–gel method. The hollow mesoporous fibers show an ultra-small diameter of around 40 nm, which is the smallest among all currently reported MBG fibers, and the resultant scaffold possesses a large specific surface area of 579.0 m2 g 1, which is the largest of all MBG products reported so far. It is believed that such ultrafine diameter and the presence of mesopores will endow the scaffold with excellent bioactivity, which makes it a promising candidate in controlled drug release and bone tissue engineering. Ó 2019 Elsevier B.V. All rights reserved.
1. Introduction Bioactive glasses (BGs) play a central role in bone regeneration due to their excellent in vitro bioactivity, osteoconductivity and osteoinductivity [1]. Recently, nanofibrous BG scaffolds have gained much interest since their structural resemblance to extracellular matrix (ECM) enables them to manipulate cell fate by providing topographical cues [2,3]. The nanofibrous BG structure provides high specific surface area which allows for rapid dissolution of ions, high protein absorption [4], controlled drug delivery [5] and osteogenic potential [4]. Accordingly, much effort has been devoted to increasing specific surface area of BG fibrous scaffolds. To date, there are two effective ways of achieving this. The first method is to induce porosity and hollowness [6,7]. The second strategy is to reduce the diameter of BG fibers. Although MBG scaffolds with small fibers can offer large surface area, the current technologies (mostly based on electrospinning) are unable to produce ultrafine BG fibers smaller than 100 nm. No report can be found in literature on hollow MBG fibers (namely nanotubes) with a diameter of less than 50 nm. ⇑ Corresponding authors at: Institute of Advanced Materials, School of Materials Science and Engineering, East China Jiaotong University, Nanchang 330013, China. E-mail addresses: [email protected] (Z. Yang), [email protected] (H. Luo). https://doi.org/10.1016/j.matlet.2019.04.041 0167-577X/Ó 2019 Elsevier B.V. All rights reserved.
In this work, we report a novel three-dimensional (3D) scaffold composed of hollow ultrafine MBG fibers (ca. 40 nm) via a facile and scalable template-assisted sol–gel method. The effects of processing variables such as ethanol to water ratio (Ve:Vw), aging time (t) and calcination temperature (T) on the structure of the scaffolds were investigated. 2. Experimental 2.1. Preparation of MBGH scaffold The hollow MBG fiber (MBGH) scaffold was prepared by template-assisted sol–gel method using bacterial cellulose (BC) and nonionic block copolymer (P123) as co-templates. In a typical process, 4 g of P123 was dissolved in 50 mL of ethanol, then 9 mL of tetraethyl orthosilicate (TEOS), 1.75 g of Ca(NO3)24H2O (CN) and 0.85 mL of triethyl phosphate (TEP) were added into the solution and stirred for 24 h. Subsequently, 125 mg of BC was immersed in the solution. After stirring for another 24 h, the obtained materials were rinsed with ethanol and then soaked in the mixture of ethanol and water with varying ratios (Ve:Vw = 6:1, 9:1 and 12:1) for 12, 24 and 36 h to undergo hydrolysis and poly-condensation. Finally, specimens were freeze-dried and calcined at 500, 600 and 700 °C for 5 h.
202
J. Xiao et al. / Materials Letters 248 (2019) 201–203
2.2. Characterizations To determine whether nanotubular structure was obtained, products were observed using transmission electron microscopy (TEM, Tecnai G2F-20) and the obtained MBGH scaffold was further characterized by scanning electron microscopy (SEM, Hitachi S4800). Energy dispersive X-ray spectroscopy (EDS) was used to qualitatively analyze the surface chemical composition of the scaffold. In addition, X-ray diffraction (XRD, Rigaku D/Max 2500 v/pc) and N2 adsorption–desorption analyses (Quantachrome NOVA 2200e) were carried out.
3. Results and discussion In the present study, we investigated the effects of processing variables including Ve:Vw, t and T on the structure of the resultant products. We find that Ve:Vw = 9:1 is the optimum value to obtain nanotubular structure (Fig. 1b), otherwise the resultants are nanofibers (Fig. 1a) and nanoparticles (Fig. 1c) when Ve:Vw = 6:1 and 12:1, respectively, due to the fact that too fast or too slow hydrolysis rate results in uncontrollable synthesis process, not favorable to obtain nanotubular structure. The aging time also has a significant impact on product structure. At t = 24 h, a typical nanotube can be obtained (Fig. 1b) while t = 12 and 36 h results in nanofibers (Fig. 1d) and nanoparticles (Fig. 1e), respectively. The results indicate that too short or too long aging time is also not favorable to obtain nanotubular structure. Similarly, nanotubular products can be obtained when T = 600 °C while nanoparticles (Fig. 1f and g) are noted at T = 500 and 700 °C. The high calcination temperature causes overheating, which can result in structural collapse, only forming the nanoparticles. Similarly, it is also difficult to create nanotubular structure at the low calcination temperature. As shown in Fig. 1h, under optimum parameters (Ve:Vw = 9:1, t = 24 h and T = 600 °C), a sound nanotubular scaffold can be obtained which almost fully inherits the 3D interconnected porous structure of BC (Fig. 1i). The resultant nanotubes show a diameter of around 40 nm and a wall thickness of 8 nm (Fig. 1b). The typical
Fig. 2. Typical fabrication process of MBGH scaffold.
fabrication process of MBGH scaffold is schematically illustrated in Fig. 2. The hydroxyl groups on the surface of BC fibers may also act as a catalyst to accelerate the hydrolysis and condensation of the precursors, thus promoting the formation of MBGH. As shown in Fig. 3a, EDS results confirm the presence of Si, Ca, P and O in MBGH scaffold. The wide-angle XRD pattern reveals the amorphous nature of MBGH scaffold since no diffraction peak is noted except for a wide SiO2 peak at 2h = 25° (Fig. 3b) [8]. The small-angle XRD pattern demonstrates an apparent diffraction peak at 2h = 0.5–1° (inset in Fig. 3b), suggesting that there are ordered mesopores in MBGH scaffold [9]. The high-resolution TEM (HRTEM) further confirms presence of mesopores (3.8 nm) in nanotube walls (Fig. 3c). Moreover, N2 adsorption–desorption result verifies typical IV isotherms and shows hysteresis loop (Fig. 3d), which is an indication of mesoporous structure, agreeing with the previous reports [10,11]. Fig. 3d suggests that MBGH scaffold possesses dual mesopore sizes of 3.9 and 15.1 nm, the former being pores in the walls and the latter being formed by neighboring nanotubes. N2 adsorption–desorption measurement reveals a large surface area of 579.0 m2 g 1. The pore size (3.9 nm) in tube walls is comparable to that of previously reported MBG powder [12] and thick MBG fibers [1] while the surface area is significantly larger than all MBG products reported so far (Table 1) [1,7,13–18], which is due to its ultra-small tube diameter than literature values (Table 1) [7,14–19]. The presence of mesopores and large surface area can significantly improve its bioactivity [20]. In addition, the bioactive agents (such as drugs and growth factors) can be incorporated into MBGH scaffold through mesopores (for small molecular drugs) [21] and the cavities of nanotubes (for big molecular growth factors). Therefore, such MBGH scaffold holds great promise in tissue engineering and regenerative medicine as well as drug delivery.
4. Conclusions
Fig. 1. (a–g) TEM images of various products prepared under different conditions. (h) SEM of MBGH prepared at optimum conditions (Ve:Vw = 9:1, t = 24 h and T = 600 °C). (i) SEM image of BC (inset shows low magnified TEM image in Fig. 1b).
We have successfully prepared a novel 3D scaffold consisting of hollow ultrafine MBG fibers (namely nanotubes) using templateassisted sol–gel method. There are ordered mesopores in the tube walls with a size of 3.9 nm. The nanotubes have an ultra-small diameter of ca. 40 nm which is the smallest among all reported values and the MBGH scaffold shows a larger specific surface area (579.0 m2 g 1) than all MBG reported so far. It is expected that the hollowness and fine fibers enable the scaffold to exhibit good
203
J. Xiao et al. / Materials Letters 248 (2019) 201–203
Fig. 3. (a) EDS elemental mapping, (b) wide-angle XRD pattern (inset shows small-angle XRD pattern), (c) HRTEM image, and (d) N2 adsorption–desorption isotherms (inset presents the pore size distribution) of MBGH scaffold.
Table 1 Comparisons of fiber diameter, specific surface area and pore size of bioactive glass prepared by different methods. Method
Outer diameter (nm)
Inner diameter (nm)
Specific surface area (m2 g 1)
Pore size (nm)
Refs.
Electrospinning
400.0 450.0 330.0 500.0 300.0 45.0
200.0 280.0 170.0 100.0 160.0 25.0
154.0 449.7 – – 52.0 579.0
2.0–9.0 1.7 – – lm 3.9
[7] [14] [15] [16] [17] this work
Collagen-template BC template
bioactivity and sustainable drug delivery, which make it very promising in the applications of tissue engineering and drug delivery. Conflict of interest None. Acknowledgements This work was supported by the National Natural Science Foundation of China (Nos. 51572187 and 30660264) and the Youth Science Foundation of Jiangxi Province (Grant no. 20181BAB216010). References [1] F.-Y. Hsu, H.-W. Hsu, Y.-H. Chang, J.-L. Yu, L.-R. Rau, S.-W. Tsai, Mater. Sci. Eng. C 89 (2018) 346–354. [2] E. Schnell, K. Klinkhammer, S. Balzer, G. Brook, D. Klee, P. Dalton, J. Mey, Biomaterials 28 (2007) 3012–3025. [3] S. Chen, S.K. Boda, S.K. Batra, X. Li, J. Xie, Adv. Healthc. Mater. 7 (2018) 1701024–1701044.
[4] C. Gao, Q. Gao, X. Bao, Y. Li, A. Teramoto, K. Abe, J. Am. Ceram. Soc. 94 (2011) 2841–2845. [5] Y. Hong, X. Chen, X. Jing, H. Fan, B. Guo, Z. Gu, X. Zhang, Adv. Mater. 22 (2010) 754–758. [6] H. Lu, T. Zhang, X.P. Wang, Q.F. Fang, J. Mater. Sci.: Mater. Med. 20 (2009) 793– 798. [7] Y. Hong, X. Chen, X. Jing, H. Fan, Z. Gu, X. Zhang, Adv. Funct. Mater. 20 (2010) 1503–1510. [8] R.F.P. Pereira, K. Zehbe, C. Gunter, T. Dos Santos, S.C. Nunes, F.A.A. Paz, M.M. Silva, P.L. Granja, A. Taubert, V. de Zea Bermudez, ACS Omega 3 (2018) 10811– 10822. [9] N. Gomez-Cerezo, E. Verron, V. Montouillout, F. Fayon, P. Lagadec, J.M. Bouler, B. Bujoli, D. Arcos, M. Vallet-Regi, Acta Biomater. 76 (2018) 333–343. [10] X. Li, X. Chen, G. Miao, H. Liu, C. Mao, G. Yuan, Q. Liang, X. Shen, C. Ning, X. Fu, J. Mater. Chem. B 2 (2014) 7045–7054. [11] X. Li, F. Qu, W. Li, H. Lin, Y. Jin, J. Sol-Gel Sci. Technol. 63 (2012) 416–424. [12] C. Wu, J. Chang, Interface Focus 2 (2012) 292–306. [13] A. El-Fiqi, J.-H. Kim, H.-W. Kim, A.C.S. Appl, Mater. Interfaces 7 (2015) 1140– 1152. [14] Z. Ma, G. Dong, C. Lv, J. Qiu, Mater. Lett. 88 (2012) 136–139. [15] B. Song, L. Wu, C. Wu, J. Chang, Biomed. Glasses 1 (2015) 136–139. [16] J. Xie, E.R. Blough, C.H. Wang, Acta Biomater. 8 (2012) 811–819. [17] S. Chen, A. Osaka, N. Hanagata, J. Mater. Chem. 21 (2011) 4332–4338. [18] W. Liu, X. Wang, X. Gao, X. Chen, X. Yu, H. Wang, X. Deng, Ceram. Int. 39 (2013) 8521–8526. [19] N. Ghaebi Panah, P. Alizadeh, B. Eftekhari Yekta, N. Motakef-Kazemi, Ceram. Int. 42 (2016) 10935–10942. [20] Y. Zhang, L. Xia, D. Zhai, M. Shi, Y. Luo, C. Feng, B. Fang, J. Yin, J. Chang, C. Wu, Nanoscale 7 (2015) 19207–19221. [21] C. Wu, Y. Zhou, J. Chang, Y. Xiao, Acta Biomater. 9 (2013) 9159–9168.