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Synthesis and characterization of Polyurethane – Titanium Dioxide – Hydroxyapatite nanocomposite for biomedical applications
Available online at www.sciencedirect.com
ScienceDirect Materials Today: Proceedings 3 (2016) 4052–4057
www.materialstoday.com/proceedings
ICMRA 2016
Synthesis and characterization of Polyurethane – Titanium Dioxide – Hydroxyapatite nanocomposite for biomedical applications A Ratnakara+ , K Hari Prasadb , S Vivekananthanc*+, P C Karthikac, Aashutosh Kumarb a
c
Centre for Nanoscience and Technology, Pondicherry University, India. b Department of Physics, Pondicherry University, Puducherry India. Department of Physics and Nanotechnology, SRM University, Chennai, India.
Abstract
Need for a stable polymeric material with an excellent biocompatibility property is the most sought one in the field of implant science and engineering. The material’s scale up requires a complex mechanism or environment or the precursors to develop the material itself require an investment, i.e. the overall process cum procedure might not be economical. Here, in this paper, an attempt has been made to synthesize, a polymer based nanocomposite comprising titanium di oxide nanoparticles and hydroxyapatite nanoparticles as fillers; distributed within a polyurethane matrix which is economical and could be scaled up easily. The same has been characterized to understand their structure, morphology, mechanical property and in vitro biocompatibility through XRD, SEM, tensile tests and simulated body fluid tests. From the characterizations it was found that, the material was stable, biocompatible under tough conditions and the material had a simple foam structure (porous) except for which the boundaries that are shared by the pores are rigid providing the material with a good mechanical strength. © 2016 Elsevier Ltd. All rights reserved. Selection and Peer-review under responsibility of International conference on materials research and applications-2016. Keywords: nanocomposite; titanium di oxide; hydroxyapatite; polyurethane matrix; in vitro biocompatibility; simulated body fluid tests; enhanced mechanical property; tensile test.
2214-7853 © 2016 Elsevier Ltd. All rights reserved. Selection and Peer-review under responsibility of International conference on materials research and applications-2016.
A. Ratnakar et al. / Materials Today: Proceedings 3 (2016) 4052–4057
4053
1. Introduction Implant science and engineering of Biomedical Science requires materials of different magnitude and properties to figure out solution for problems that circles around designing an implant (both active, passive devices and structural implants), NEMS, MEMS, membranes as filters for bio-fluids, etc., [1], [2]. Much of the focuses are on eliminating the use of engineered glasses, metals and alloys to design and construct an implant [3]. Especially, the active implant devices such as ventricular assist devices and the passive implants such as stents, eye lens etc. [4], [5]. The materials either interact with the immune system directly or they setup conditions that force the immune system to react [3]. While focusing on the other research domains of biomedical science, researchers are focusing on developing nonmetallic materials that could act as filters or act as a scaffold or behave like an artificial muscle etc. [6]. Most of the polymers preferred for biomed, biotech, biomechanical applications are the well-known PMMA, PVP, PVA, PCL, etc., and their blends and crosslinks [7]. The reported polymers, their crosslinks, blends and blends of crosslinks vice versa have all been presently used for a wide range of applications such as coatings for implants, carriers/vehicles for drug delivery, transdermal patches, cosmetic implants etc. [8-10]. These polymers possess wide range of properties as a bulk structure but most of them fail when they are used to design a microstructure [11]. In this research work, an attempt has been made to synthesize a nanocomposite using titanium di oxide (TiO 2) nanoparticles and hydroxyapatite (HAp) nanoparticles as fillers within a polyurethane matrix to obtain a porous biocompatible material with good mechanical properties. 1.1. Importance of titanium dioxide and hydroxyapatite nanoparticles as filler materials Titanium dioxide (TiO2) and hydroxyapatite (HAp) nanoparticles are the most researched and reported materials for their multidisciplinary applications such as coatings for implants, as drug carriers/vehicles in targeted drug delivery or bio imaging [12-14]. While hydroxyapatite nanoparticles have been the best biocompatible and bone equivalent material for almost five decades of biomedical science research works [15], [16]. The hydroxyapatite’s needle shapes have been engineered by various optimized protocols to obtain HAps with enhanced morphology and reactive surface [17]. These nanoparticles with varied morphologies are preferred to develop direct tissue contact transdermal patches which can act as a drug carrier as well as a tissue regenerator.
2. Experimental
The TiO2 nanoparticles and HAp nanoparticles were synthesized by the methods described in [18] and [19]. Necessary modifications were made to the protocol with respect to the change in temperature, pH level of the sols, stirring duration and drying conditions for better or same output. 0.5g of the synthesized TiO 2 nanoparticles and 2.5g HAp nanoparticles were introduced into optimized quantities of Polytetramethylene ether glycol (PTMEG), toluene diisocyanate (TDI) respectively. The PTMEG gets a milky white tone while the TDI acquires a dirt white color. The PTMEG and TDI are stirred individually using a mechanical stirrer to enable even distribution of the nanoparticles within the solution. 1,4-butanediol (chain extender) and DABCO (hardener) were added to the PTMEG with TiO 2 particles and TDI with HAp nanoparticles respectively. TDI with HAp and DABCO was added to PTMEG with TiO2 particles and TDI. The overall temperature generated during the interaction of the two solutions was controlled using an ice bath to slow down the hardening process. When sufficient viscosity was achieved the mixture was quickly transferred to the polystyrene templates to form the ASTM D3039 standard specimen. The specimens were then subjected characterizations to study their properties after they were dried at room temperature for 80 hours with a load of 1 ton, temporarily sealing the open side of the templates.
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A. Ratnakar et al. / Materials Today: Proceedings 3 (2016) 4052–4057
Fig. 1. XRD graph obtained for the nanocomposite (PU-TiO2-HAp)
3. Results and discussion 3.1 X-Ray Diffraction (XRD) The XRD result, Fig.1., obtained for the nanocomposites were all amorphous which could be due to the presence of excess polymer matrix than the nanoparticles. The amorphous peaks could also be due to the fact that the nanoparticles were firmly encapsulated and bounded by the polyurethane, preventing the diffraction process. From the result it can also be concluded that the polyurethane did not get crystallized or semi crystallized during the one step synthesis process. 3.2 FE-Scanning Electron Microscope (FE-SEM) The morphology of the synthesized nanocomposite was observed under FE-SEM to explore the structure of the nanocomposite. From Fig.2, it can be noticed that the synthesized nanocomposite is extremely porous. It can also be noticed that the pores are in relation with the other pores (pores within pores) which could possibly be the best explanation for the low mass of the nanocomposite. The presence of pores also confirms the fact that the synthesized polymer based composite could be an ideal material for collecting biofluids or storing drug, etc., if they are biocompatible. 3.3 Tensile tests Tensile property of the prepared material (according to ASTM D3039) was studied by subjecting the sample to tensometer tests. The samples were fixed to one end through a holder while the other end was pulled through an assembly which enables a gradual and equal elongation within a sample. The loads which resulted in fracture were
A. Ratnakar et al. / Materials Today: Proceedings 3 (2016) 4052–4057
4055
Fig. 2. Morphology of the synthesized nanocomposite through FE-SEM noted down and necessary corrections were added to define factor of safety. From the graph Fig.3., it can be noticed, the nanocomposite has the ability to withstand 17.6 MPa of load which makes the polymer very much suitable for load bearing applications. The nanocomposites were prepared as per ASTM D3039.
Fig. 3. Graph obtained from the microtenso meter explaining the tensile strength
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A. Ratnakar et al. / Materials Today: Proceedings 3 (2016) 4052–4057
3.4 Simulated Body Fluid Test (SBF) The synthesized nanocomposites were cut into pieces and were subjected to SBF tests. SBF solutions were prepared as per the stand protocol followed by other researchers. The SBF solutions were changed once in every 25 hours. The tests were carried out for 24 days and 17 hours. The samples were recovered and dried immediately. Presence of some aggregates was noticed within the pores and on the surface of the polymer boundaries that link the pores. These aggregates were isolated from the nanocomposites and were subjected to EDS to analyze their composition. Since the nanocomposite had hydroxyapatites embedded within the structure, subjecting the whole sample to EDS could mislead the investigation process.
3.5 Energy Dispersive X Ray analyses (EDS) The EDS was carried out to confirm the composition of the aggregates that were present in the pores and on the surface of the nanocomposite. From Fig.4., it can be concluded that the aggregates formed are hydroxyapatite proving the biocompatibility of the synthesized polyurethane matrix based titanium dioxide and hydroxyapatite nanoparticles.
Fig. 4. EDS of the aggregates isolated from the nanocomposites that were subjected to simulated body fluid tests for 24 days. 4. Conclusions A porous polyurethane based TiO2 and HAp nanocomposite was developed by a simple one step synthesis process. From the SEM, SBF tests and tensile tests it can be concluded that the synthesized nanocomposite has reasonable porous structure, mechanical properties and biocompatibility respectively, making the nanocomposite a suitable material for a wide range of applications such filtering bio-fluids such as blood, CSF etc., and for applications that require a cushioning applications or load bearing applications (6-12Mpa). It can also be noted that the synthesis process can be scaled up with simple improvisations which can result in mass production of the material.
A. Ratnakar et al. / Materials Today: Proceedings 3 (2016) 4052–4057
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Acknowledgement The corresponding author and the co-authors are profoundly grateful to the Nanotechnology Research Center, SRM University and Material Science and Characterization Laboratory, Department of Physics & Nanotechnology, SRM University for their assistance in carrying out the experimentation and characterizing the samples. The authors also express their gratitude to Material testing lab of Tagore Engineering College for their assistance in performing hardness and tensometer tests. +Both the authors have contributed/are contributing equally for the outcomes of this research work. References [1] Soumya Nag and Rajarshi Banerjee. ASM Handbook, Vol. 23 (2012). [2] Irena Gotman, Ph.D., Characteristics of Metals Used in Implants. Journal of Endourology, Vol. 11, No. 6, (1997). [3] J.P. Simon, G. Fabry, ActaOrthopedicaBelgia, Vol 57-1 (1991). [4] Anne Strohbach and Raila Busch, Vol 2015, Article ID 782653, 11, (2015). [5] Robert C. Eberhart, Shih-Horngsu, Kytai Truong Nguyen, Meital Zilberman, Liping Tang, Kevin D. Nelson and Peter Frenkel, J. Biomater. Sci. Polymer Edn, Vol. 14, No. 4, pp. 299–312 (2003). [6] Yariv Cohen: Biofiltration, Bioresource Technology 77,257-274(2001). [7] Deller RC, Vatish M, Mitchell DA, Gibson MI: Synthetic polymers enable non-vitreous cellular cryopreservation by reducing ice crystal growth during thawing, Nat Commun.,5:3244, (2014). [8] Ravinder Kaur, Mrs. Sukhvir Kaur, J. of Drug Delivery and Therapeutics, 4(3), 32-36 (2014). [9] Sateesh Kandavilli, Vinod Nair, and Ramesh Panchagnula, Pharmaceutical Technology (2002). [10] Francisco López-Huerta, Blanca Cervantes, Octavio González, Julián Hernández-Torres, Leandro García-González, Rosario Vega, Agustín L. Herrera-May and Enrique Soto, Materials, 7, 4105-4117 (2014). [11] Jin Huanga, Ping Dong, WeichangHaob, Tianmin Wangb, YayiXiac, Guozu Dad, Yubo Fana, Applied Surface Science 313, 172–182(2014). [14] V. J. Sawant and R. V. Kupwade, Der Pharmacia Lettre, 7 (6), 37-44 (2015). [15] Kiyoshi Kanie and TadaoSugimoto,Chem. Commu.1584-1585 (2004). [16] Huanan Wang, Yubao Li, Yi Zuo, Jihua Li, Sansi Ma, Lin Cheng, Biomaterials, 28, 3338–3348(2007). [17] Ming Li, Yanbo Wang, Qian Liu, QiuhongLi, Yan Cheng, Yufeng Zheng, Tingfei Xia and Shicheng Wei, J. Mater. Chem. B, 1, 475 (2013). [18] Zhihong Dong, Yubao Li, Qin Zou, Applied Surface Science 255, 6087–6091(2009). [19] Khan AS, Ahmed Z, Edirisinghe MJ, Wong FSL, Rehman IU, ActaBiomater, 4 (5) 1275 – 1287 (2008). [20] Haimei Liu, Wensheng Yang, Ying Ma, Yaan Cao, Jiannian Yao, Jing Zhang and Tiandou Hu, Langmuir, 19, 3001-3005 (2003). [21] Naruporn Monmaturapoj, Journal of Metals, Materials and Minerals. Vol.18 No.,15-20 (2008).
ScienceDirect Materials Today: Proceedings 3 (2016) 4052–4057
www.materialstoday.com/proceedings
ICMRA 2016
Synthesis and characterization of Polyurethane – Titanium Dioxide – Hydroxyapatite nanocomposite for biomedical applications A Ratnakara+ , K Hari Prasadb , S Vivekananthanc*+, P C Karthikac, Aashutosh Kumarb a
c
Centre for Nanoscience and Technology, Pondicherry University, India. b Department of Physics, Pondicherry University, Puducherry India. Department of Physics and Nanotechnology, SRM University, Chennai, India.
Abstract
Need for a stable polymeric material with an excellent biocompatibility property is the most sought one in the field of implant science and engineering. The material’s scale up requires a complex mechanism or environment or the precursors to develop the material itself require an investment, i.e. the overall process cum procedure might not be economical. Here, in this paper, an attempt has been made to synthesize, a polymer based nanocomposite comprising titanium di oxide nanoparticles and hydroxyapatite nanoparticles as fillers; distributed within a polyurethane matrix which is economical and could be scaled up easily. The same has been characterized to understand their structure, morphology, mechanical property and in vitro biocompatibility through XRD, SEM, tensile tests and simulated body fluid tests. From the characterizations it was found that, the material was stable, biocompatible under tough conditions and the material had a simple foam structure (porous) except for which the boundaries that are shared by the pores are rigid providing the material with a good mechanical strength. © 2016 Elsevier Ltd. All rights reserved. Selection and Peer-review under responsibility of International conference on materials research and applications-2016. Keywords: nanocomposite; titanium di oxide; hydroxyapatite; polyurethane matrix; in vitro biocompatibility; simulated body fluid tests; enhanced mechanical property; tensile test.
2214-7853 © 2016 Elsevier Ltd. All rights reserved. Selection and Peer-review under responsibility of International conference on materials research and applications-2016.
A. Ratnakar et al. / Materials Today: Proceedings 3 (2016) 4052–4057
4053
1. Introduction Implant science and engineering of Biomedical Science requires materials of different magnitude and properties to figure out solution for problems that circles around designing an implant (both active, passive devices and structural implants), NEMS, MEMS, membranes as filters for bio-fluids, etc., [1], [2]. Much of the focuses are on eliminating the use of engineered glasses, metals and alloys to design and construct an implant [3]. Especially, the active implant devices such as ventricular assist devices and the passive implants such as stents, eye lens etc. [4], [5]. The materials either interact with the immune system directly or they setup conditions that force the immune system to react [3]. While focusing on the other research domains of biomedical science, researchers are focusing on developing nonmetallic materials that could act as filters or act as a scaffold or behave like an artificial muscle etc. [6]. Most of the polymers preferred for biomed, biotech, biomechanical applications are the well-known PMMA, PVP, PVA, PCL, etc., and their blends and crosslinks [7]. The reported polymers, their crosslinks, blends and blends of crosslinks vice versa have all been presently used for a wide range of applications such as coatings for implants, carriers/vehicles for drug delivery, transdermal patches, cosmetic implants etc. [8-10]. These polymers possess wide range of properties as a bulk structure but most of them fail when they are used to design a microstructure [11]. In this research work, an attempt has been made to synthesize a nanocomposite using titanium di oxide (TiO 2) nanoparticles and hydroxyapatite (HAp) nanoparticles as fillers within a polyurethane matrix to obtain a porous biocompatible material with good mechanical properties. 1.1. Importance of titanium dioxide and hydroxyapatite nanoparticles as filler materials Titanium dioxide (TiO2) and hydroxyapatite (HAp) nanoparticles are the most researched and reported materials for their multidisciplinary applications such as coatings for implants, as drug carriers/vehicles in targeted drug delivery or bio imaging [12-14]. While hydroxyapatite nanoparticles have been the best biocompatible and bone equivalent material for almost five decades of biomedical science research works [15], [16]. The hydroxyapatite’s needle shapes have been engineered by various optimized protocols to obtain HAps with enhanced morphology and reactive surface [17]. These nanoparticles with varied morphologies are preferred to develop direct tissue contact transdermal patches which can act as a drug carrier as well as a tissue regenerator.
2. Experimental
The TiO2 nanoparticles and HAp nanoparticles were synthesized by the methods described in [18] and [19]. Necessary modifications were made to the protocol with respect to the change in temperature, pH level of the sols, stirring duration and drying conditions for better or same output. 0.5g of the synthesized TiO 2 nanoparticles and 2.5g HAp nanoparticles were introduced into optimized quantities of Polytetramethylene ether glycol (PTMEG), toluene diisocyanate (TDI) respectively. The PTMEG gets a milky white tone while the TDI acquires a dirt white color. The PTMEG and TDI are stirred individually using a mechanical stirrer to enable even distribution of the nanoparticles within the solution. 1,4-butanediol (chain extender) and DABCO (hardener) were added to the PTMEG with TiO 2 particles and TDI with HAp nanoparticles respectively. TDI with HAp and DABCO was added to PTMEG with TiO2 particles and TDI. The overall temperature generated during the interaction of the two solutions was controlled using an ice bath to slow down the hardening process. When sufficient viscosity was achieved the mixture was quickly transferred to the polystyrene templates to form the ASTM D3039 standard specimen. The specimens were then subjected characterizations to study their properties after they were dried at room temperature for 80 hours with a load of 1 ton, temporarily sealing the open side of the templates.
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A. Ratnakar et al. / Materials Today: Proceedings 3 (2016) 4052–4057
Fig. 1. XRD graph obtained for the nanocomposite (PU-TiO2-HAp)
3. Results and discussion 3.1 X-Ray Diffraction (XRD) The XRD result, Fig.1., obtained for the nanocomposites were all amorphous which could be due to the presence of excess polymer matrix than the nanoparticles. The amorphous peaks could also be due to the fact that the nanoparticles were firmly encapsulated and bounded by the polyurethane, preventing the diffraction process. From the result it can also be concluded that the polyurethane did not get crystallized or semi crystallized during the one step synthesis process. 3.2 FE-Scanning Electron Microscope (FE-SEM) The morphology of the synthesized nanocomposite was observed under FE-SEM to explore the structure of the nanocomposite. From Fig.2, it can be noticed that the synthesized nanocomposite is extremely porous. It can also be noticed that the pores are in relation with the other pores (pores within pores) which could possibly be the best explanation for the low mass of the nanocomposite. The presence of pores also confirms the fact that the synthesized polymer based composite could be an ideal material for collecting biofluids or storing drug, etc., if they are biocompatible. 3.3 Tensile tests Tensile property of the prepared material (according to ASTM D3039) was studied by subjecting the sample to tensometer tests. The samples were fixed to one end through a holder while the other end was pulled through an assembly which enables a gradual and equal elongation within a sample. The loads which resulted in fracture were
A. Ratnakar et al. / Materials Today: Proceedings 3 (2016) 4052–4057
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Fig. 2. Morphology of the synthesized nanocomposite through FE-SEM noted down and necessary corrections were added to define factor of safety. From the graph Fig.3., it can be noticed, the nanocomposite has the ability to withstand 17.6 MPa of load which makes the polymer very much suitable for load bearing applications. The nanocomposites were prepared as per ASTM D3039.
Fig. 3. Graph obtained from the microtenso meter explaining the tensile strength
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A. Ratnakar et al. / Materials Today: Proceedings 3 (2016) 4052–4057
3.4 Simulated Body Fluid Test (SBF) The synthesized nanocomposites were cut into pieces and were subjected to SBF tests. SBF solutions were prepared as per the stand protocol followed by other researchers. The SBF solutions were changed once in every 25 hours. The tests were carried out for 24 days and 17 hours. The samples were recovered and dried immediately. Presence of some aggregates was noticed within the pores and on the surface of the polymer boundaries that link the pores. These aggregates were isolated from the nanocomposites and were subjected to EDS to analyze their composition. Since the nanocomposite had hydroxyapatites embedded within the structure, subjecting the whole sample to EDS could mislead the investigation process.
3.5 Energy Dispersive X Ray analyses (EDS) The EDS was carried out to confirm the composition of the aggregates that were present in the pores and on the surface of the nanocomposite. From Fig.4., it can be concluded that the aggregates formed are hydroxyapatite proving the biocompatibility of the synthesized polyurethane matrix based titanium dioxide and hydroxyapatite nanoparticles.
Fig. 4. EDS of the aggregates isolated from the nanocomposites that were subjected to simulated body fluid tests for 24 days. 4. Conclusions A porous polyurethane based TiO2 and HAp nanocomposite was developed by a simple one step synthesis process. From the SEM, SBF tests and tensile tests it can be concluded that the synthesized nanocomposite has reasonable porous structure, mechanical properties and biocompatibility respectively, making the nanocomposite a suitable material for a wide range of applications such filtering bio-fluids such as blood, CSF etc., and for applications that require a cushioning applications or load bearing applications (6-12Mpa). It can also be noted that the synthesis process can be scaled up with simple improvisations which can result in mass production of the material.
A. Ratnakar et al. / Materials Today: Proceedings 3 (2016) 4052–4057
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Acknowledgement The corresponding author and the co-authors are profoundly grateful to the Nanotechnology Research Center, SRM University and Material Science and Characterization Laboratory, Department of Physics & Nanotechnology, SRM University for their assistance in carrying out the experimentation and characterizing the samples. The authors also express their gratitude to Material testing lab of Tagore Engineering College for their assistance in performing hardness and tensometer tests. +Both the authors have contributed/are contributing equally for the outcomes of this research work. References [1] Soumya Nag and Rajarshi Banerjee. ASM Handbook, Vol. 23 (2012). [2] Irena Gotman, Ph.D., Characteristics of Metals Used in Implants. Journal of Endourology, Vol. 11, No. 6, (1997). [3] J.P. Simon, G. Fabry, ActaOrthopedicaBelgia, Vol 57-1 (1991). [4] Anne Strohbach and Raila Busch, Vol 2015, Article ID 782653, 11, (2015). [5] Robert C. Eberhart, Shih-Horngsu, Kytai Truong Nguyen, Meital Zilberman, Liping Tang, Kevin D. Nelson and Peter Frenkel, J. Biomater. Sci. Polymer Edn, Vol. 14, No. 4, pp. 299–312 (2003). [6] Yariv Cohen: Biofiltration, Bioresource Technology 77,257-274(2001). [7] Deller RC, Vatish M, Mitchell DA, Gibson MI: Synthetic polymers enable non-vitreous cellular cryopreservation by reducing ice crystal growth during thawing, Nat Commun.,5:3244, (2014). [8] Ravinder Kaur, Mrs. Sukhvir Kaur, J. of Drug Delivery and Therapeutics, 4(3), 32-36 (2014). [9] Sateesh Kandavilli, Vinod Nair, and Ramesh Panchagnula, Pharmaceutical Technology (2002). [10] Francisco López-Huerta, Blanca Cervantes, Octavio González, Julián Hernández-Torres, Leandro García-González, Rosario Vega, Agustín L. Herrera-May and Enrique Soto, Materials, 7, 4105-4117 (2014). [11] Jin Huanga, Ping Dong, WeichangHaob, Tianmin Wangb, YayiXiac, Guozu Dad, Yubo Fana, Applied Surface Science 313, 172–182(2014). [14] V. J. Sawant and R. V. Kupwade, Der Pharmacia Lettre, 7 (6), 37-44 (2015). [15] Kiyoshi Kanie and TadaoSugimoto,Chem. Commu.1584-1585 (2004). [16] Huanan Wang, Yubao Li, Yi Zuo, Jihua Li, Sansi Ma, Lin Cheng, Biomaterials, 28, 3338–3348(2007). [17] Ming Li, Yanbo Wang, Qian Liu, QiuhongLi, Yan Cheng, Yufeng Zheng, Tingfei Xia and Shicheng Wei, J. Mater. Chem. B, 1, 475 (2013). [18] Zhihong Dong, Yubao Li, Qin Zou, Applied Surface Science 255, 6087–6091(2009). [19] Khan AS, Ahmed Z, Edirisinghe MJ, Wong FSL, Rehman IU, ActaBiomater, 4 (5) 1275 – 1287 (2008). [20] Haimei Liu, Wensheng Yang, Ying Ma, Yaan Cao, Jiannian Yao, Jing Zhang and Tiandou Hu, Langmuir, 19, 3001-3005 (2003). [21] Naruporn Monmaturapoj, Journal of Metals, Materials and Minerals. Vol.18 No.,15-20 (2008).