Reinforcement of polyetheretherketone polymer with titanium for improved mechanical properties and in vitro biocompatibility Hyun-Do Jung,1,2* Hui-Sun Park,1* Min-Ho Kang,1 Yuanlong Li,1 Hyoun-Ee Kim,1 Young-Hag Koh,3 Yuri Estrin4,5 1
Department of Materials Science and Engineering, Seoul National University, Seoul 151-742, Korea Liquid Processing & Casting Technology R&D Group, Korea Institute of Industrial Technology, Incheon 406-840, Korea 3 School of Biomedical Engineering, Korea University, Seoul 136-703, Korea 4 Centre for Advanced Hybrid Materials, Department of Materials Engineering, Monash University, Clayton, Victoria 3800, Australia 5 Laboratory for Hybrid Nanostructured Materials, NITU MISiS, Moscow, Russia 2
Received 22 May 2014; revised 26 October 2014; accepted 9 December 2014 Published online 00 Month 2014 in Wiley Online Library (wileyonlinelibrary.com). DOI: 10.1002/jbm.b.33361 Abstract: Blends of ductile Ti metal with polyetheretherketone (PEEK) polymer were studied with regard to their mechanical properties and in vitro biocompatibility. PEEK/Ti composites with various Ti contents, ranging from 0 vol % to 60 vol %, were produced by compression molding at 370 C. In all composites produced, regardless of the initial Ti content, Ti particles were well distributed in the PEEK matrix. Addition of Ti led to a significant increase in mechanical properties of PEEK. Specifically, an increase in Ti content enhanced compressive strength and stiffness, while preserv-
ing ductile fracture behavior. In addition, the use of Ti for reinforcement of PEEK provided the composites with improved in vitro biocompatibility in terms of the attachment, C 2015 proliferation, and differentiation of MC3T3-E1 cells. V Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 00B: 000–000, 2015.
Key Words: polymers, metals, particle-reinforced composites, mechanical properties, powder processing
How to cite this article: Jung, H-D, Park, H-S, Kang, M-H, Li, Y, Kim, H-E, Koh, Y-H, Estrin, Y. 2015. Reinforcement of polyetheretherketone polymer with titanium for improved mechanical properties and in vitro biocompatibility. J Biomed Mater Res Part B 2015:00B:000–000.
INTRODUCTION
Recent decades saw a rapid increase in the use of orthopedic implants for treating back and spine impairments, which are the primary cause of restricted activity.1–4 As implant materials, polyetheretherketone (PEEK), one of the most widely used biocompatible polymers, has great advantages over traditional metallic implant materials. For example, PEEK polymer has a much lower stiffness (3–4 GPa) than metals, which can effectively mitigate the risk of bone resorption and implant loosening during services.5–8 In addition, the bone healing process around PEEK implants can be visualized using conventional medical imaging systems, such as magnetic resonance imaging (MRI) and computer tomography (CT).9–12 On the other hand, bare PEEK polymer has limited biocompatibility/bioactivity in vitro and in vivo, which limits its wider application in orthopedic implants. This is why considerable effort has been made to incorporate bioactive ceramics, including calcium phosphate (CaP) ceramics and
bioactive glasses, as a reinforcement into PEEK implants.13–16 However, one of the problems associated with the use of brittle ceramic reinforcements is a drastic reduction in mechanical strength for large volume fractions of ceramics.17,18 In general, the mechanical properties and the biological performance of these composites are strongly affected by the amount of reinforcements as well as their properties.15,19,20 In this article, we demonstrate that an alternative approach, viz., the use of ductile Ti metal as a novel reinforcement leads to improved mechanical properties while at the same time enhancing the in vitro biocompatibility of PEEK implants. Titanium was selected as a ductile reinforcement owing to its high specific strength, relatively low stiffness, and outstanding biocompatibility—a combination of properties that makes Ti superior to most other bio-metals.21,22 PEEK/Ti composites with various Ti contents (0 vol %, 15 vol %, 30 vol %, 45 vol %, and 60 vol %) were produced by compression molding at 370 C with an uniaxial
*Both authors contributed equally to this work. Correspondence to: Y. H. Koh; e-mail: [email protected] Contract grant sponsor: The Technology Innovation Program funded by the Ministry of Knowledge Economy; contract grant number: 10037915 Contract grant sponsor: Russian Ministry for Education and Science; contract grant number: 14.A12.31.0001
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FIGURE 1. (A) SEM image of the Ti powders used as the reinformecent and (B) particle size distribution.
load of 350 MPa. The microstructure and crystal structure of PEEK/Ti composites were investigated, while their mechanical properties were examined by compressive and tensile strength tests. The in vitro biocompatibility of PEEK/ Ti composites was also evaluated in terms of attachment, proliferation, and differentiation of pre-osteoblast MC3T3E1 cells. MATERIALS AND METHODS
Starting materials Commercially available PEEK powder (450PF, Victrex USA Inc., Greenville, SC) with a mean particle size of 50 mm and Ti powder (2325 mesh, Alfa Aesar, Ward Hill, MA) were used as the starting materials. The morphology of the Ti powders was characterized by field emission scanning electron microscopy (FE-SEM, JSM-6360, JEOL, Tokyo, Japan) and their particle size distribution was examined by a particle size analyzer (CILAS 1090 L, USA). PEEK/Ti composite production PEEK/Ti mixtures with various Ti contents (0 vol %, 15 vol %, 30 vol %, 45 vol %, and 60 vol %) were prepared by mechanically blending PEEK and Ti powders via dry ballmilling without balls for 1 h. The prepared PEEK/Ti mixtures were then dried overnight at 70 C to remove any moisture. The resultant PEEK/Ti mixtures were put in a rigid die with a diameter of 12 mm and compressed at
370 C under a uniaxial load of 350 MPa for 30 min. The produced PEEK/Ti composites were polished and ultrasonically cleaned in acetone, ethanol, and distilled water in sequence.
Microstructure and crystal structure evaluation The microstructure of PEEK/Ti composites was evaluated by FE-SEM. Back-scattered electron (BSE) mode during FESEM observations was also employed to distinguish the Ti particles from the PEEK matrix. The crystal structure of the composites was characterized by X-ray diffraction (XRD, D8Advance, BRUKER, Germany) using a monochromatic Cu Ka radiation. The samples were scanned over a diffraction angle range from 20 to 60 at a scanning rate of 1 /min.
Crystallinity evaluation The crystallinity of the PEEK/Ti composites with various Ti contents (0 vol %, 15 vol %, 30 vol %, 45 vol %, and 60 vol %) was characterized by differential scanning calorimeter (DSC, DSC Q1000, TA Instrument, UK). The samples were heated up to 390 C at a heating rate of 10 C/min in a flowing nitrogen atmosphere and then cooled to room temperature. The crystallinity (Xc) of the PEEK polymer was calculated by considering the following equation.23
FIGURE 2. Optical image of the PEEK/Ti composites with various Ti contents (0 vol %, 15 vol %, 30 vol %, 45 vol %, and 60 vol %). [Color figure can be viewed in the online issue, which is available at wileyonlinelibrary.com.]
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TI AS REINFORCEMENT IN PEEK FOR IMPROVED MECHANICAL AND BIOLOGICAL PROPERTIES
ORIGINAL RESEARCH REPORT
FIGURE 3. SEM images of the PEEK/Ti composites with various Ti contents: (A) 15 vol %, (B) 30 vol %, (C) 45 vol %, and (D) 60 vol %.
Xc ð%Þ ¼ DHm =ðDHo 3WPEEK Þ3100
(1)
where DHm is the melting enthalpy for the PEEK/Ti composite, WPEEK is the weight percentage of the PEEK, and DHo (130 J/g) is the melting enthalpy for 100% crystalline PEEK polymer. Testing of mechanical properties To evaluate the mechanical properties of PEEK/Ti composites, compressive and tensile strength tests were conducted in accordance with ASTM D69517,24 and ASTM 638,17,23,25 respectively. Cylindrical specimens with a diameter of 12 mm and a height of 20 mm were compressed uniaxially at a constant cross-head speed of 2 mm/min in a screw-driven testing machine (Instron 5565, Instron Corp., Canton, MA). In addition, specimens with a thickness of 1.5 mm and a gauge length of 10 mm were elongated uniaxially at a constant cross-head speed of 1 mm/min. The stress and strain responses of the specimens were monitored throughout the compressive and tensile strength tests. Five specimens were tested to obtain sufficient statistics of the measurements. The fractured surfaces of the samples were examined by SEM. In vitro biocompatibility tests The in vitro biocompatibility of PEEK/Ti composites was evaluated in terms of cell attachment, proliferation, and differentiation using pre-osteoblasts MC3T3-E1 cells (ATCC, CRL-2593, USA). Pre-incubated cells were seeded onto the specimens with densities of 5 3 104 cells/mL, 1 3 104 cells/mL, and 2.5 3 103 cells/mL for the cell-attachment,
cell-proliferation, and cell-differentiation assays, respectively. The cells were cultured in a medium consisting of an aminimum essential medium (a-MEM, Welgene Co., Seoul, Korea) supplemented with 5% fetal bovine serum (FBS) and 1% penicillin–streptomycin in a humidified incubator with 5% CO2 at 37 C. The morphologies of the attached cells on PEEK/Ti composites were examined using SEM. After 3 h of culturing, the cells on the substrates were fixed with 2.5%
FIGURE 4. XRD patterns of the PEEK/Ti composites with various Ti contents: (A) 0 vol %, (B) 15 vol %, (C) 30 vol %, (D) 45 vol %, and (E) 60 vol %. 䉬 PEEK and |: Ti). [Color figure can be viewed in the online issue, which is available at wileyonlinelibrary.com.]
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TABLE I. Crystallinity (Xc) of the PEEK/Ti Composites With Various Ti Contents (0 vol %, 15 vol %, 30 vol %, 45 vol %, and 60 vol %) Ti Content (wt %) Crystallinity, XC (%)
0 21.8
15 17.5
30 9.3
45 9.0
60 8.7
glutaraldehyde and then dehydrated in a graded ethanol series (75, 90, 95, and 100% ethanol). The cell proliferation rate was examined using an MTS (methoxyphenyl tetrazolium salt) assay with 3-(4, 5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl) -2H-tetrazolium (MTS, Promega, Madison, WI) for mitochondrial reduction. After culturing for 3 and 5 days, the quantity of the formazan product, which was measured in terms of the light absorbance at the wavelength of 490 nm using a micro-reader (Model 550; Biorad, USA), was directly proportional to the number of living cells in the culture. Cell differentiation was assessed using an alkaline phosphatase (ALP) activity test, in which 10 mM bglycerophosphate (b-GP) and 50 mg/mL ascorbic acid (AA) were added to the culture medium. After culturing for 7 days, p-nitrophenol (pNP) production was colorimetrically measured in terms of the light absorbance at the wavelength of 405 nm using a micro reader (Model 550;Biorad, USA). During this reaction, pNPP was converted to pNP in the presence of ALP; therefore, the pNP production rate was proportional to the ALP activity. Magnetic resonance imaging scan The compatibility of the PEEK/Ti composites with magnetic resonance imaging (MRI) was evaluated using a 3.0 T MRI scanner (Discovery MR 750, GE Healthcare, USA). For comparison purposes, the bare PEEK and Ti were also tested. The specimens, 12 mm in diameter and 1 mm in thickness, were implanted in cadaveric pigs. Subsequently, the porcine models were scanned using MRI. Statistical analysis Experimental data were expressed in terms of values 6 standard deviation (SD) values. Statistical evaluation was performed using a one-way analysis of variance (ANOVA) and p
FIGURE 5. Representative compressive stress vs. strain curves for the PEEK/Ti composites with various Ti contents: (A) 0 vol %, (B) 15 vol %, (C) 30 vol %, (D) 45 vol %, and (E) 60 vol %. [Color figure can be viewed in the online issue, which is available at wileyonlinelibrary.com.]
values less than 0.05 were considered to be statistically significant. RESULTS AND DISCUSSION
Ti powders as reinforcement The mechanical properties of the polymer-based composites are strongly affected by the fraction of reinforcement and its distribution in the polymer matrix.13 In this study, relatively coarse Ti particles with a mean size (D50) of 26.63 lm were used as the reinforcement, as shown in Figure 1(A,B). This approach would allow the coarse Ti particles to be well mixed with the PEEK powders via simple dry ballmilling. In addition, relatively large Ti particles would effectively withstand applied compressive and/or tensile loads because of their ductility, which would, accordingly, lead to considerably enhanced mechanical properties. Morphology and microstructure PEEK/Ti composites with various Ti contents (0 vol %, 15 vol %, 30 vol %, 45 vol %, and 60 vol %) were produced by compression molding at 370 C, a temperature slightly in excess of the melting point of PEEK (Tm 5 343 C), under an
FIGURE 6. (A) Compressive strength, (B) compressive elastic modulus, and (C) strain at failure for the PEEK/Ti composites with various Ti contents (0 vol %, 15 vol %, 30 vol %, 45 vol %, and 60 vol %). [Color figure can be viewed in the online issue, which is available at wileyonlinelibrary.com.]
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FIGURE 7. BSE images of the fracture surfaces of the PEEK/Ti composites with various Ti contents: (A) 30 vol %, (B) 45 vol %, and (C) 60 vol %.
applied load of 350 MPa. Figure 2 shows the representative optical image of the PEEK/Ti composites. As seen in the figure, all the composites produced, regardless of the Ti content, showed no noticeably large defects, such as voids or cracks. The physical appearance of the composites varied with the composition, that is, as they became darker with an increase in the Ti content. Figure 3(A–D) shows the representative SEM micrographs of the PEEK/Ti composites with various Ti contents. For all Ti composites, the Ti particles, appearing bright on the micrographs, were well dispersed in the PEEK matrix and did not show any pronounced agglomeration. However, some relatively large cavities were observed, which were presumably generated by the detachment of Ti particles as a result of polishing for SEM specimen preparation.
Crystal structure The crystallographic structure of the PEEK/Ti composites were examined by XRD, as shown in Figure 4(A–E). While the bare PEEK sample showed only peaks corresponding to those of the crystalline PEEK polymer [Figure 4(A)], additional strong peaks associated with the crystalline Ti were found for the PEEK/Ti composites [Figure 4(B–E)]. The relative intensities of these peaks increased substantially with an increase in Ti content. No other peaks were observed,
suggesting that the crystalline structures of the PEEK and Ti phases were not affected by compression molding at 370 C. Crystallinity of PEEK/Ti composites The crystallinity of the PEEK/Ti composites with various Ti contents (0 vol %, 15 vol %, 30 vol %, 45 vol %, and 60 vol %), which was calculated by differential scanning calorimeter (DSC), is summarized in Table I. The degree of crystallization decreased from 21.8% to 8.7% with increasing Ti content from 0 vol % to 60 vol %, presumably due to the high thermal conductivity of Ti metal. It should be noted that the crystallinity of the PEEK polymer would be expected to affect the mechanical properties of the PEEK/Ti composites produced. Mechanical properties For evaluating the potential applications of the PEEK/Ti composites as orthopedic implants, their mechanical properties were examined by compressive and tensile strength tests. Figure 5(A–E) shows the typical compressive stress versus strain curves of the PEEK/Ti composites with various Ti contents. For all Ti contents, the samples exhibited ductile fracture behavior, that is, an initial elastic deformation was followed by a considerable amount of plastic strain before fracture. It should be noted that even the PEEK/Ti composite with a Ti content as high as 60 vol % still
FIGURE 8. (A) Ultimate tensile strength and (B) tensile modulus for the PEEK/Ti composites with various Ti contents (0 vol %, 15 vol %, 30 vol %, 45 vol %, and 60 vol %).
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FIGURE 9. SEM images of the MC3T3-E1 cells that were cultured for 3 h on the PEEK/Ti composites with various Ti contents: (A) 0 vol %, (B) 15 vol %, (C) 30 vol %, (D) 45 vol %, and (E) 60 vol %.
possessed a fair amount of ductility, which is unobtainable when brittle ceramics are used as reinforcement. Figure 6(A–C) presents compressive strength, stiffness, and strain at failure of the PEEK/Ti composites. As the Ti content increased from 0 vol % to 60 vol %, the compressive strength and stiffness of the composites increased significantly: from 132 6 12 MPa to 246 6 9 MPa and from 3.1 6 0.1 GPa to 7.7 6 0.3 GPa, respectively. It should be noted that these values compare favorably to the compressive strength (106–215 MPa) and stiffness (16–23 GPa) of natural cortical bone.26–28 It is remarkable that the strain at failure did not change much with an increase in Ti content from 0 vol % to 30 vol %, and was in the range of 17.4%– 17.7%. On the other hand, higher Ti contents (40 vol %) led to a decrease in strain at failure. However, it should be noted that the strains at failure obtained in this study are much higher than those for ceramic-reinforced PEEK composites, such as, for example, HA whisker-reinforced PEEK, which has a relatively low value of 3%.25,29
The fracture surfaces of the PEEK/Ti composites were examined by SEM to interpret their fracture behavior under compression. Figure 7(A–C) shows the representative BSE images of the samples with various Ti contents (30 vol %, 45 vol %, and 60 vol %) after compressive strength tests. The samples with a Ti content of 30 vol % revealed relatively smooth fracture surface without noticeable large deboning at the Ti/PEEK interface [Figure 6(A)], suggesting the relative strong bonding between the Ti and PEEK phases. However, when higher Ti contents (40 vol %) were used, the samples revealed a number of Ti particles exposed [Figure 6(B,C)] due to the very high stiffness of Ti metal compared to the PEEK polymer. The mechanical properties of the PEEK/Ti composites were also evaluated by tensile strength tests. The ultimate tensile strength and tensile modulus are shown in Figures 8(A,B), respectively. The samples with Ti contents 30 vol % and 40 vol % showed much higher ultimate tensile strengths [Figure 7(A)] and tensile modulus [Figure 7(B)]
FIGURE 10. (A) Cell viability and (B) ALP activity of the MC3T3-E1 cells that were cultured for 5 days and 7 days on the PEEK/Ti composites with various Ti contents (0 vol %, 15 vol %, 30 vol %, 45 vol %, and 60 vol %). (* 5 p < 0.05, ** 5 p < 0.005). [Color figure can be viewed in the online issue, which is available at wileyonlinelibrary.com.]
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FIGURE 11. MRI images of (A) the bare PEEK, (B) PEEK/Ti composite with a Ti content of 45 vol %, and (C) bare Ti.
than the PEEK polymer. These great improvements were mainly attributed to the use of ductile Ti metal as the reinforcement, which can be hardly obtainable using brittle ceramic fillers. More specifically, Ti particles in the PEEK/Ti composites can very effectively withstand the applied load under tension because of their good ductility but with high stiffness. However, further detailed studies on the relationship of mechanical properties under multiple loading conditions should be carried out for verifying the utility of the PEEK/Ti composites produced in this study as the loadbearing implants. In vitro biocompatibility The in vitro biocompatibility of the PEEK/Ti composites with various Ti contents was examined using in vitro cell tests. Figure 9(A–E) shows the representative SEM images of the composites after 3 h of MC3T3-E1 cell culturing. Generally, none of the composites showed any signs of cytotoxicity. However, for bare PEEK, cells with a relatively round shape that poorly adhered to and spread onto its surface were observed [Figure 9(A)]. By contrast, cells showed filopodia extensions and flattened morphology on the surfaces of the Ti- reinforced composites [Figure 9(B–E)]. Furthermore, it was observed that the cells preferentially adhered to and spread on the Ti particles, suggesting that Ti may provide more biocompatible surface for the initial cell attachment.30 The degree of cell proliferation on the PEEK/Ti composites after 5 days of cell culturing was examined using an MTS assay, as shown in Figure 10(A). The Ti- reinforced composites showed significantly larger absorbance values (p < 0.05) than did the bare PEEK. In addition, similar to the cell proliferation behavior, after 7 days of culturing, significantly higher ALP activity levels were observed for the Ti- reinforced composites, compare Figure 10(B). Moreover, the ALP activity continuously increased with an increase in Ti content up to 45 vol %. These findings suggest that the reinforcement of PEEK polymer with Ti metal can significantly facilitate the attachment, proliferation, and differentiation of MC3T3-E1 cells in vitro, which would be expected to provide enhanced osseointegration ability in vivo.31 Compatibility with MRI One of the most striking advantages of PEEK polymer is its excellent compatibility with conventional medical imaging
systems, such as MRI and CT, which allows for the bone healing process around implants to be monitored.9–12 It was thereof of importance to investigate how the addition of Ti affects the possibility of medical imaging of PEEK. Figure 11(A–C) shows typical MRI images of the bare PEEK, PEEK/ Ti composite with a Ti content of 45 vol %, and bare Ti. The bare PEEK showed negligible artifacts on a MRI scan, which represented the original geometry of the implanted PEEK faithfully [Figure 11(A)]. By contrast, the bare Ti showed severe artifacts on a MRI scan, as is often the case with traditional metallic implants [Figure 11(C)]. However, the PEEK/Ti composite with a high Ti content of 45 vol % still retained reasonable compatibility with MRI, although some artifacts occurred around the edges of the implants [Figure 11(B)]. These findings suggest that the use of Ti metal as reinforcement would only slightly reduce the excellent compatibility of PEEK with MRI and would still allow visualization of tissue/bone growth.
CONCLUSIONS
Titanium metal was used as ductile reinforcement for enhancing the mechanical properties and the in vitro biocompatibility of PEEK polymer. Simple compression molding at 370 C allowed the production of relatively dense PEEK/ Ti composites with good dispersion of Ti particles in PEEK matrixes. With an increase in Ti content from 0 vol % to 60 vol %, the compressive strength of the composites rose significantly from 132 6 12 MPa to 246 6 9 MPa and the stiffness increased from 3.1 6 0.1 GPa to 7.7 6 0.3 GPa, while preserving good compressive ductility. In addition, the composites with Ti contents of 30 vol % and 45 vol % showed much higher ultimate tensile strength and modulus than the pure PEEK polymer. The cell variability and the ALP activity also increased significantly with an increase in Ti content. These findings indicate that the use of Ti as a ductile reinforcement could significantly enhance the mechanical properties and in vitro biocompatibility of PEEK polymer. This favorable combination of properties of the PEEK/Ti composites can potentially be used in orthopedic implants. REFERENCES 1. Praemer A, Furner S, Rice DP. Musculoskeletal Conditions in the United States: Park Ridge: American Academy of Orthopaedic Surgeons; 1992.
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2. Toth JM, Wang M, Estes BT, Scifert JL, Seim HB, Turner AS. Polyetheretherketone as a biomaterial for spinal applications. Biomaterials 2006;27:324–334. 3. Andersson GB. Epidemiological features of chronic low-back pain. Lancet 1999;354:581–585. 4. Kuslich SD, Ulstrom CL, Griffith SL, Ahern JW, Dowdle JD. The Bagby and Kuslich method of lumbar interbody fusion: History, techniques, and 2-year follow-up results of a United States prospective, multicenter trial. Spine 1998;23:1267–1278. 5. Wenz L, Merritt K, Brown S, Moet A, Steffee A. In vitro biocompatibility of polyetheretherketone and polysulfone composites. J Biomed Mater Res 1990;24:207–215. 6. Katzer A, Marquardt H, Westendorf J, Wening J, Von Foerster G. Polyetheretherketone-cytotoxicity and mutagenicity in vitro. Biomaterials 2002;23:1749–1759. 7. Kurtz SM, Devine JN. PEEK biomaterials in trauma, orthopedic, and spinal implants. Biomaterials 2007;28:4845–4869. 8. Cho D.Y, Liau WR, Lee WY, Liu JT, Chiu CL, Sheu PC. Preliminary experience using a polyetheretherketone (PEEK) cage in the treatment of cervical disc disease. Neurosurgery 2002;51:1343–1350. € hn T, Krause H, Voges U, 9. Hempel E, Fischer H, Gumb L, Ho Breitwieser H, Gutmann B, Durke J, Bock M, Melzer A. An MRIcompatible surgical robot for precise radiological interventions. Comput Aided Surg 2003;8:180–191. [PMC][15360099] 10. Schulte M, Schultheiss M, Hartwig E, Wilke H-J, Wolf S, Sokiranski R, Fleiter T, Kinzl L, Claes L. Vertebral body replacement with a bioglass-polyurethane composite in spine metastases-clinical, radiological and biomechanical results. Eur Spine J 2000;9:437–444. 11. Ernstberger T, Heidrich G, Schultz W, Grabbe E. Implant detectibility of intervertebral disc spacers in post fusion MRI: Evaluation of the MRI scan quality by using a scoring system-an in vitro study. Neuroradiology 2007;49:103–109. 12. Cutler AR, Siddiqui S, Avinash L M, Hillard VH, Cerabona F, Das K. Comparison of polyetheretherketone cages with femoral cortical bone allograft as a single-piece interbody spacer in transforaminal lumbar interbody fusion. J Neurosurg Spine 2006;5:534–539. 13. Diez-Pascual AM, Naffakh M, Marco C, Ellis G, Gomez-Fatou MA. High-performance nanocomposites based on polyetherketones. Prog Mater Sci 2012;57:1106–1190. 14. Tang S, Cheang P, AbuBakar M, Khor K, Liao K. Tension–tension fatigue behavior of hydroxyapatite reinforced polyetheretherketone composites. Int J Fat 2004;26:49–57. 15. Kane RJ, Converse GL, Roeder RK. Effects of the reinforcement morphology on the fatigue properties of hydroxyapatite reinforced polymers J Mech Behav Biomed 2008;1:261–268. 16. Roeder RK, Smith SM, Conrad TL, Yanchak NJ, Merrill CH, Converse GL. Porous and bioactive PEEK implants for interbody spinal fusion. Adv Mater Process 2009;167:46–48.
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17. Bakar A, Cheang P, Khor K. Mechanical properties of injection molded hydroxyapatite-polyetheretherketone biocomposites. Comp Sci Technol 2003;63:421–425. 18. Hengky C, Kelsen B, Cheang P. Mechanical and biological characterization of pressureless sintered hydroxapatite-polyetheretherketone biocomposite. ICBME 2008, Singapore, 2009, Vol. 23. pp 261–264. 19. Williams D, McNamara A, Turner R. Potential of polyetheretherketone (PEEK) and carbon-fibre-reinforced PEEK in medical applications. J Mater Sci Lett 1987;6:188–190. 20. Ma R, Weng L, Fang L, Luo Z, Song S. Structure and mechanical performance of in situ synthesized hydroxyapatite/polyetheretherketone nanocomposite materials. J Sol gel Sci Technol 2012;62: 52–56. 21. Long M, Rack H. Titanium alloys in total joint replacement—A materials science perspective. Biomaterials 1998;19:1621–1639. 22. Jung HD, Yook SW, Jang TS, Li Y, Kim HE, Koh YH. Dynamic freeze casting for the production of porous titanium (Ti) scaffolds. Mater Sci Eng C 2013;33:59–63. 23. Sarasua J, Remiro P, Pouyet J. The mechanical behaviour of PEEK short fibre composites. J Mater Sci 1995;30:3501–3508. 24. Ferguson SJ, Visser JMA, Polikeit A. The long-term mechanical integrity of non-reinforced PEEK-OPTIMA polymer for demanding spinal applications: Experimental and finite-element analysis. Eur Spine J 2006;15:149–156. 25. Converse GL, Yue W, Roeder RK. Processing and tensile properties of hydroxyapatite-whisker-reinforced polyetheretherketone. Biomaterials 2007;28:927–935. 26. Ashman R, Cowin S, Van Buskirk W, Rice J. A continuous wave technique for the measurement of the elastic properties of cortical bone. J Biomech 1984;17:349–361. [PMC][6736070] 27. Yaszemski MJ, Payne RG, Hayes WC, Langer R, Mikos AG. Evolution of bone transplantation: Molecular, cellular and tissue strategies to engineer human bone. Biomaterials 1996;17:175– 185. 28. Rho JY, Kuhn-Spearing L, Zioupos P. Mechanical properties and the hierarchical structure of bone. Med Eng Phys 1998;20:92– 102. 29. Roeder RK, Sproul MM, Turner CH. Hydroxyapatite whiskers provide improved mechanical properties in reinforced polymer composites. J Biomed Mater Res A 2003;67:801–812. 30. Wu X, Liu X, Wei J, Ma J, Deng F, Wei S. Nano-TiO2/PEEK bioactive composite as a bone substitute material: In vitro and in vivo studies. Int J Nanomed 2012;7:1215–1225. 31. Olivares-Navarrete R, Gittens RA, Schneider JM, Hyzy SL, Haithcock DA, Ullrich PF, Schwartz Z, Boyan BD. Osteoblasts exhibit a more differentiated phenotype and increased bone morphogenetic protein production on titanium alloy substrates than on poly-ether-ether-ketone. Spine J 2012;12:265–272.
TI AS REINFORCEMENT IN PEEK FOR IMPROVED MECHANICAL AND BIOLOGICAL PROPERTIES
Department of Materials Science and Engineering, Seoul National University, Seoul 151-742, Korea Liquid Processing & Casting Technology R&D Group, Korea Institute of Industrial Technology, Incheon 406-840, Korea 3 School of Biomedical Engineering, Korea University, Seoul 136-703, Korea 4 Centre for Advanced Hybrid Materials, Department of Materials Engineering, Monash University, Clayton, Victoria 3800, Australia 5 Laboratory for Hybrid Nanostructured Materials, NITU MISiS, Moscow, Russia 2
Received 22 May 2014; revised 26 October 2014; accepted 9 December 2014 Published online 00 Month 2014 in Wiley Online Library (wileyonlinelibrary.com). DOI: 10.1002/jbm.b.33361 Abstract: Blends of ductile Ti metal with polyetheretherketone (PEEK) polymer were studied with regard to their mechanical properties and in vitro biocompatibility. PEEK/Ti composites with various Ti contents, ranging from 0 vol % to 60 vol %, were produced by compression molding at 370 C. In all composites produced, regardless of the initial Ti content, Ti particles were well distributed in the PEEK matrix. Addition of Ti led to a significant increase in mechanical properties of PEEK. Specifically, an increase in Ti content enhanced compressive strength and stiffness, while preserv-
ing ductile fracture behavior. In addition, the use of Ti for reinforcement of PEEK provided the composites with improved in vitro biocompatibility in terms of the attachment, C 2015 proliferation, and differentiation of MC3T3-E1 cells. V Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 00B: 000–000, 2015.
Key Words: polymers, metals, particle-reinforced composites, mechanical properties, powder processing
How to cite this article: Jung, H-D, Park, H-S, Kang, M-H, Li, Y, Kim, H-E, Koh, Y-H, Estrin, Y. 2015. Reinforcement of polyetheretherketone polymer with titanium for improved mechanical properties and in vitro biocompatibility. J Biomed Mater Res Part B 2015:00B:000–000.
INTRODUCTION
Recent decades saw a rapid increase in the use of orthopedic implants for treating back and spine impairments, which are the primary cause of restricted activity.1–4 As implant materials, polyetheretherketone (PEEK), one of the most widely used biocompatible polymers, has great advantages over traditional metallic implant materials. For example, PEEK polymer has a much lower stiffness (3–4 GPa) than metals, which can effectively mitigate the risk of bone resorption and implant loosening during services.5–8 In addition, the bone healing process around PEEK implants can be visualized using conventional medical imaging systems, such as magnetic resonance imaging (MRI) and computer tomography (CT).9–12 On the other hand, bare PEEK polymer has limited biocompatibility/bioactivity in vitro and in vivo, which limits its wider application in orthopedic implants. This is why considerable effort has been made to incorporate bioactive ceramics, including calcium phosphate (CaP) ceramics and
bioactive glasses, as a reinforcement into PEEK implants.13–16 However, one of the problems associated with the use of brittle ceramic reinforcements is a drastic reduction in mechanical strength for large volume fractions of ceramics.17,18 In general, the mechanical properties and the biological performance of these composites are strongly affected by the amount of reinforcements as well as their properties.15,19,20 In this article, we demonstrate that an alternative approach, viz., the use of ductile Ti metal as a novel reinforcement leads to improved mechanical properties while at the same time enhancing the in vitro biocompatibility of PEEK implants. Titanium was selected as a ductile reinforcement owing to its high specific strength, relatively low stiffness, and outstanding biocompatibility—a combination of properties that makes Ti superior to most other bio-metals.21,22 PEEK/Ti composites with various Ti contents (0 vol %, 15 vol %, 30 vol %, 45 vol %, and 60 vol %) were produced by compression molding at 370 C with an uniaxial
*Both authors contributed equally to this work. Correspondence to: Y. H. Koh; e-mail: [email protected] Contract grant sponsor: The Technology Innovation Program funded by the Ministry of Knowledge Economy; contract grant number: 10037915 Contract grant sponsor: Russian Ministry for Education and Science; contract grant number: 14.A12.31.0001
C 2015 WILEY PERIODICALS, INC. V
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FIGURE 1. (A) SEM image of the Ti powders used as the reinformecent and (B) particle size distribution.
load of 350 MPa. The microstructure and crystal structure of PEEK/Ti composites were investigated, while their mechanical properties were examined by compressive and tensile strength tests. The in vitro biocompatibility of PEEK/ Ti composites was also evaluated in terms of attachment, proliferation, and differentiation of pre-osteoblast MC3T3E1 cells. MATERIALS AND METHODS
Starting materials Commercially available PEEK powder (450PF, Victrex USA Inc., Greenville, SC) with a mean particle size of 50 mm and Ti powder (2325 mesh, Alfa Aesar, Ward Hill, MA) were used as the starting materials. The morphology of the Ti powders was characterized by field emission scanning electron microscopy (FE-SEM, JSM-6360, JEOL, Tokyo, Japan) and their particle size distribution was examined by a particle size analyzer (CILAS 1090 L, USA). PEEK/Ti composite production PEEK/Ti mixtures with various Ti contents (0 vol %, 15 vol %, 30 vol %, 45 vol %, and 60 vol %) were prepared by mechanically blending PEEK and Ti powders via dry ballmilling without balls for 1 h. The prepared PEEK/Ti mixtures were then dried overnight at 70 C to remove any moisture. The resultant PEEK/Ti mixtures were put in a rigid die with a diameter of 12 mm and compressed at
370 C under a uniaxial load of 350 MPa for 30 min. The produced PEEK/Ti composites were polished and ultrasonically cleaned in acetone, ethanol, and distilled water in sequence.
Microstructure and crystal structure evaluation The microstructure of PEEK/Ti composites was evaluated by FE-SEM. Back-scattered electron (BSE) mode during FESEM observations was also employed to distinguish the Ti particles from the PEEK matrix. The crystal structure of the composites was characterized by X-ray diffraction (XRD, D8Advance, BRUKER, Germany) using a monochromatic Cu Ka radiation. The samples were scanned over a diffraction angle range from 20 to 60 at a scanning rate of 1 /min.
Crystallinity evaluation The crystallinity of the PEEK/Ti composites with various Ti contents (0 vol %, 15 vol %, 30 vol %, 45 vol %, and 60 vol %) was characterized by differential scanning calorimeter (DSC, DSC Q1000, TA Instrument, UK). The samples were heated up to 390 C at a heating rate of 10 C/min in a flowing nitrogen atmosphere and then cooled to room temperature. The crystallinity (Xc) of the PEEK polymer was calculated by considering the following equation.23
FIGURE 2. Optical image of the PEEK/Ti composites with various Ti contents (0 vol %, 15 vol %, 30 vol %, 45 vol %, and 60 vol %). [Color figure can be viewed in the online issue, which is available at wileyonlinelibrary.com.]
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TI AS REINFORCEMENT IN PEEK FOR IMPROVED MECHANICAL AND BIOLOGICAL PROPERTIES
ORIGINAL RESEARCH REPORT
FIGURE 3. SEM images of the PEEK/Ti composites with various Ti contents: (A) 15 vol %, (B) 30 vol %, (C) 45 vol %, and (D) 60 vol %.
Xc ð%Þ ¼ DHm =ðDHo 3WPEEK Þ3100
(1)
where DHm is the melting enthalpy for the PEEK/Ti composite, WPEEK is the weight percentage of the PEEK, and DHo (130 J/g) is the melting enthalpy for 100% crystalline PEEK polymer. Testing of mechanical properties To evaluate the mechanical properties of PEEK/Ti composites, compressive and tensile strength tests were conducted in accordance with ASTM D69517,24 and ASTM 638,17,23,25 respectively. Cylindrical specimens with a diameter of 12 mm and a height of 20 mm were compressed uniaxially at a constant cross-head speed of 2 mm/min in a screw-driven testing machine (Instron 5565, Instron Corp., Canton, MA). In addition, specimens with a thickness of 1.5 mm and a gauge length of 10 mm were elongated uniaxially at a constant cross-head speed of 1 mm/min. The stress and strain responses of the specimens were monitored throughout the compressive and tensile strength tests. Five specimens were tested to obtain sufficient statistics of the measurements. The fractured surfaces of the samples were examined by SEM. In vitro biocompatibility tests The in vitro biocompatibility of PEEK/Ti composites was evaluated in terms of cell attachment, proliferation, and differentiation using pre-osteoblasts MC3T3-E1 cells (ATCC, CRL-2593, USA). Pre-incubated cells were seeded onto the specimens with densities of 5 3 104 cells/mL, 1 3 104 cells/mL, and 2.5 3 103 cells/mL for the cell-attachment,
cell-proliferation, and cell-differentiation assays, respectively. The cells were cultured in a medium consisting of an aminimum essential medium (a-MEM, Welgene Co., Seoul, Korea) supplemented with 5% fetal bovine serum (FBS) and 1% penicillin–streptomycin in a humidified incubator with 5% CO2 at 37 C. The morphologies of the attached cells on PEEK/Ti composites were examined using SEM. After 3 h of culturing, the cells on the substrates were fixed with 2.5%
FIGURE 4. XRD patterns of the PEEK/Ti composites with various Ti contents: (A) 0 vol %, (B) 15 vol %, (C) 30 vol %, (D) 45 vol %, and (E) 60 vol %. 䉬 PEEK and |: Ti). [Color figure can be viewed in the online issue, which is available at wileyonlinelibrary.com.]
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TABLE I. Crystallinity (Xc) of the PEEK/Ti Composites With Various Ti Contents (0 vol %, 15 vol %, 30 vol %, 45 vol %, and 60 vol %) Ti Content (wt %) Crystallinity, XC (%)
0 21.8
15 17.5
30 9.3
45 9.0
60 8.7
glutaraldehyde and then dehydrated in a graded ethanol series (75, 90, 95, and 100% ethanol). The cell proliferation rate was examined using an MTS (methoxyphenyl tetrazolium salt) assay with 3-(4, 5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl) -2H-tetrazolium (MTS, Promega, Madison, WI) for mitochondrial reduction. After culturing for 3 and 5 days, the quantity of the formazan product, which was measured in terms of the light absorbance at the wavelength of 490 nm using a micro-reader (Model 550; Biorad, USA), was directly proportional to the number of living cells in the culture. Cell differentiation was assessed using an alkaline phosphatase (ALP) activity test, in which 10 mM bglycerophosphate (b-GP) and 50 mg/mL ascorbic acid (AA) were added to the culture medium. After culturing for 7 days, p-nitrophenol (pNP) production was colorimetrically measured in terms of the light absorbance at the wavelength of 405 nm using a micro reader (Model 550;Biorad, USA). During this reaction, pNPP was converted to pNP in the presence of ALP; therefore, the pNP production rate was proportional to the ALP activity. Magnetic resonance imaging scan The compatibility of the PEEK/Ti composites with magnetic resonance imaging (MRI) was evaluated using a 3.0 T MRI scanner (Discovery MR 750, GE Healthcare, USA). For comparison purposes, the bare PEEK and Ti were also tested. The specimens, 12 mm in diameter and 1 mm in thickness, were implanted in cadaveric pigs. Subsequently, the porcine models were scanned using MRI. Statistical analysis Experimental data were expressed in terms of values 6 standard deviation (SD) values. Statistical evaluation was performed using a one-way analysis of variance (ANOVA) and p
FIGURE 5. Representative compressive stress vs. strain curves for the PEEK/Ti composites with various Ti contents: (A) 0 vol %, (B) 15 vol %, (C) 30 vol %, (D) 45 vol %, and (E) 60 vol %. [Color figure can be viewed in the online issue, which is available at wileyonlinelibrary.com.]
values less than 0.05 were considered to be statistically significant. RESULTS AND DISCUSSION
Ti powders as reinforcement The mechanical properties of the polymer-based composites are strongly affected by the fraction of reinforcement and its distribution in the polymer matrix.13 In this study, relatively coarse Ti particles with a mean size (D50) of 26.63 lm were used as the reinforcement, as shown in Figure 1(A,B). This approach would allow the coarse Ti particles to be well mixed with the PEEK powders via simple dry ballmilling. In addition, relatively large Ti particles would effectively withstand applied compressive and/or tensile loads because of their ductility, which would, accordingly, lead to considerably enhanced mechanical properties. Morphology and microstructure PEEK/Ti composites with various Ti contents (0 vol %, 15 vol %, 30 vol %, 45 vol %, and 60 vol %) were produced by compression molding at 370 C, a temperature slightly in excess of the melting point of PEEK (Tm 5 343 C), under an
FIGURE 6. (A) Compressive strength, (B) compressive elastic modulus, and (C) strain at failure for the PEEK/Ti composites with various Ti contents (0 vol %, 15 vol %, 30 vol %, 45 vol %, and 60 vol %). [Color figure can be viewed in the online issue, which is available at wileyonlinelibrary.com.]
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TI AS REINFORCEMENT IN PEEK FOR IMPROVED MECHANICAL AND BIOLOGICAL PROPERTIES
ORIGINAL RESEARCH REPORT
FIGURE 7. BSE images of the fracture surfaces of the PEEK/Ti composites with various Ti contents: (A) 30 vol %, (B) 45 vol %, and (C) 60 vol %.
applied load of 350 MPa. Figure 2 shows the representative optical image of the PEEK/Ti composites. As seen in the figure, all the composites produced, regardless of the Ti content, showed no noticeably large defects, such as voids or cracks. The physical appearance of the composites varied with the composition, that is, as they became darker with an increase in the Ti content. Figure 3(A–D) shows the representative SEM micrographs of the PEEK/Ti composites with various Ti contents. For all Ti composites, the Ti particles, appearing bright on the micrographs, were well dispersed in the PEEK matrix and did not show any pronounced agglomeration. However, some relatively large cavities were observed, which were presumably generated by the detachment of Ti particles as a result of polishing for SEM specimen preparation.
Crystal structure The crystallographic structure of the PEEK/Ti composites were examined by XRD, as shown in Figure 4(A–E). While the bare PEEK sample showed only peaks corresponding to those of the crystalline PEEK polymer [Figure 4(A)], additional strong peaks associated with the crystalline Ti were found for the PEEK/Ti composites [Figure 4(B–E)]. The relative intensities of these peaks increased substantially with an increase in Ti content. No other peaks were observed,
suggesting that the crystalline structures of the PEEK and Ti phases were not affected by compression molding at 370 C. Crystallinity of PEEK/Ti composites The crystallinity of the PEEK/Ti composites with various Ti contents (0 vol %, 15 vol %, 30 vol %, 45 vol %, and 60 vol %), which was calculated by differential scanning calorimeter (DSC), is summarized in Table I. The degree of crystallization decreased from 21.8% to 8.7% with increasing Ti content from 0 vol % to 60 vol %, presumably due to the high thermal conductivity of Ti metal. It should be noted that the crystallinity of the PEEK polymer would be expected to affect the mechanical properties of the PEEK/Ti composites produced. Mechanical properties For evaluating the potential applications of the PEEK/Ti composites as orthopedic implants, their mechanical properties were examined by compressive and tensile strength tests. Figure 5(A–E) shows the typical compressive stress versus strain curves of the PEEK/Ti composites with various Ti contents. For all Ti contents, the samples exhibited ductile fracture behavior, that is, an initial elastic deformation was followed by a considerable amount of plastic strain before fracture. It should be noted that even the PEEK/Ti composite with a Ti content as high as 60 vol % still
FIGURE 8. (A) Ultimate tensile strength and (B) tensile modulus for the PEEK/Ti composites with various Ti contents (0 vol %, 15 vol %, 30 vol %, 45 vol %, and 60 vol %).
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FIGURE 9. SEM images of the MC3T3-E1 cells that were cultured for 3 h on the PEEK/Ti composites with various Ti contents: (A) 0 vol %, (B) 15 vol %, (C) 30 vol %, (D) 45 vol %, and (E) 60 vol %.
possessed a fair amount of ductility, which is unobtainable when brittle ceramics are used as reinforcement. Figure 6(A–C) presents compressive strength, stiffness, and strain at failure of the PEEK/Ti composites. As the Ti content increased from 0 vol % to 60 vol %, the compressive strength and stiffness of the composites increased significantly: from 132 6 12 MPa to 246 6 9 MPa and from 3.1 6 0.1 GPa to 7.7 6 0.3 GPa, respectively. It should be noted that these values compare favorably to the compressive strength (106–215 MPa) and stiffness (16–23 GPa) of natural cortical bone.26–28 It is remarkable that the strain at failure did not change much with an increase in Ti content from 0 vol % to 30 vol %, and was in the range of 17.4%– 17.7%. On the other hand, higher Ti contents (40 vol %) led to a decrease in strain at failure. However, it should be noted that the strains at failure obtained in this study are much higher than those for ceramic-reinforced PEEK composites, such as, for example, HA whisker-reinforced PEEK, which has a relatively low value of 3%.25,29
The fracture surfaces of the PEEK/Ti composites were examined by SEM to interpret their fracture behavior under compression. Figure 7(A–C) shows the representative BSE images of the samples with various Ti contents (30 vol %, 45 vol %, and 60 vol %) after compressive strength tests. The samples with a Ti content of 30 vol % revealed relatively smooth fracture surface without noticeable large deboning at the Ti/PEEK interface [Figure 6(A)], suggesting the relative strong bonding between the Ti and PEEK phases. However, when higher Ti contents (40 vol %) were used, the samples revealed a number of Ti particles exposed [Figure 6(B,C)] due to the very high stiffness of Ti metal compared to the PEEK polymer. The mechanical properties of the PEEK/Ti composites were also evaluated by tensile strength tests. The ultimate tensile strength and tensile modulus are shown in Figures 8(A,B), respectively. The samples with Ti contents 30 vol % and 40 vol % showed much higher ultimate tensile strengths [Figure 7(A)] and tensile modulus [Figure 7(B)]
FIGURE 10. (A) Cell viability and (B) ALP activity of the MC3T3-E1 cells that were cultured for 5 days and 7 days on the PEEK/Ti composites with various Ti contents (0 vol %, 15 vol %, 30 vol %, 45 vol %, and 60 vol %). (* 5 p < 0.05, ** 5 p < 0.005). [Color figure can be viewed in the online issue, which is available at wileyonlinelibrary.com.]
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ORIGINAL RESEARCH REPORT
FIGURE 11. MRI images of (A) the bare PEEK, (B) PEEK/Ti composite with a Ti content of 45 vol %, and (C) bare Ti.
than the PEEK polymer. These great improvements were mainly attributed to the use of ductile Ti metal as the reinforcement, which can be hardly obtainable using brittle ceramic fillers. More specifically, Ti particles in the PEEK/Ti composites can very effectively withstand the applied load under tension because of their good ductility but with high stiffness. However, further detailed studies on the relationship of mechanical properties under multiple loading conditions should be carried out for verifying the utility of the PEEK/Ti composites produced in this study as the loadbearing implants. In vitro biocompatibility The in vitro biocompatibility of the PEEK/Ti composites with various Ti contents was examined using in vitro cell tests. Figure 9(A–E) shows the representative SEM images of the composites after 3 h of MC3T3-E1 cell culturing. Generally, none of the composites showed any signs of cytotoxicity. However, for bare PEEK, cells with a relatively round shape that poorly adhered to and spread onto its surface were observed [Figure 9(A)]. By contrast, cells showed filopodia extensions and flattened morphology on the surfaces of the Ti- reinforced composites [Figure 9(B–E)]. Furthermore, it was observed that the cells preferentially adhered to and spread on the Ti particles, suggesting that Ti may provide more biocompatible surface for the initial cell attachment.30 The degree of cell proliferation on the PEEK/Ti composites after 5 days of cell culturing was examined using an MTS assay, as shown in Figure 10(A). The Ti- reinforced composites showed significantly larger absorbance values (p < 0.05) than did the bare PEEK. In addition, similar to the cell proliferation behavior, after 7 days of culturing, significantly higher ALP activity levels were observed for the Ti- reinforced composites, compare Figure 10(B). Moreover, the ALP activity continuously increased with an increase in Ti content up to 45 vol %. These findings suggest that the reinforcement of PEEK polymer with Ti metal can significantly facilitate the attachment, proliferation, and differentiation of MC3T3-E1 cells in vitro, which would be expected to provide enhanced osseointegration ability in vivo.31 Compatibility with MRI One of the most striking advantages of PEEK polymer is its excellent compatibility with conventional medical imaging
systems, such as MRI and CT, which allows for the bone healing process around implants to be monitored.9–12 It was thereof of importance to investigate how the addition of Ti affects the possibility of medical imaging of PEEK. Figure 11(A–C) shows typical MRI images of the bare PEEK, PEEK/ Ti composite with a Ti content of 45 vol %, and bare Ti. The bare PEEK showed negligible artifacts on a MRI scan, which represented the original geometry of the implanted PEEK faithfully [Figure 11(A)]. By contrast, the bare Ti showed severe artifacts on a MRI scan, as is often the case with traditional metallic implants [Figure 11(C)]. However, the PEEK/Ti composite with a high Ti content of 45 vol % still retained reasonable compatibility with MRI, although some artifacts occurred around the edges of the implants [Figure 11(B)]. These findings suggest that the use of Ti metal as reinforcement would only slightly reduce the excellent compatibility of PEEK with MRI and would still allow visualization of tissue/bone growth.
CONCLUSIONS
Titanium metal was used as ductile reinforcement for enhancing the mechanical properties and the in vitro biocompatibility of PEEK polymer. Simple compression molding at 370 C allowed the production of relatively dense PEEK/ Ti composites with good dispersion of Ti particles in PEEK matrixes. With an increase in Ti content from 0 vol % to 60 vol %, the compressive strength of the composites rose significantly from 132 6 12 MPa to 246 6 9 MPa and the stiffness increased from 3.1 6 0.1 GPa to 7.7 6 0.3 GPa, while preserving good compressive ductility. In addition, the composites with Ti contents of 30 vol % and 45 vol % showed much higher ultimate tensile strength and modulus than the pure PEEK polymer. The cell variability and the ALP activity also increased significantly with an increase in Ti content. These findings indicate that the use of Ti as a ductile reinforcement could significantly enhance the mechanical properties and in vitro biocompatibility of PEEK polymer. This favorable combination of properties of the PEEK/Ti composites can potentially be used in orthopedic implants. REFERENCES 1. Praemer A, Furner S, Rice DP. Musculoskeletal Conditions in the United States: Park Ridge: American Academy of Orthopaedic Surgeons; 1992.
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2. Toth JM, Wang M, Estes BT, Scifert JL, Seim HB, Turner AS. Polyetheretherketone as a biomaterial for spinal applications. Biomaterials 2006;27:324–334. 3. Andersson GB. Epidemiological features of chronic low-back pain. Lancet 1999;354:581–585. 4. Kuslich SD, Ulstrom CL, Griffith SL, Ahern JW, Dowdle JD. The Bagby and Kuslich method of lumbar interbody fusion: History, techniques, and 2-year follow-up results of a United States prospective, multicenter trial. Spine 1998;23:1267–1278. 5. Wenz L, Merritt K, Brown S, Moet A, Steffee A. In vitro biocompatibility of polyetheretherketone and polysulfone composites. J Biomed Mater Res 1990;24:207–215. 6. Katzer A, Marquardt H, Westendorf J, Wening J, Von Foerster G. Polyetheretherketone-cytotoxicity and mutagenicity in vitro. Biomaterials 2002;23:1749–1759. 7. Kurtz SM, Devine JN. PEEK biomaterials in trauma, orthopedic, and spinal implants. Biomaterials 2007;28:4845–4869. 8. Cho D.Y, Liau WR, Lee WY, Liu JT, Chiu CL, Sheu PC. Preliminary experience using a polyetheretherketone (PEEK) cage in the treatment of cervical disc disease. Neurosurgery 2002;51:1343–1350. € hn T, Krause H, Voges U, 9. Hempel E, Fischer H, Gumb L, Ho Breitwieser H, Gutmann B, Durke J, Bock M, Melzer A. An MRIcompatible surgical robot for precise radiological interventions. Comput Aided Surg 2003;8:180–191. [PMC][15360099] 10. Schulte M, Schultheiss M, Hartwig E, Wilke H-J, Wolf S, Sokiranski R, Fleiter T, Kinzl L, Claes L. Vertebral body replacement with a bioglass-polyurethane composite in spine metastases-clinical, radiological and biomechanical results. Eur Spine J 2000;9:437–444. 11. Ernstberger T, Heidrich G, Schultz W, Grabbe E. Implant detectibility of intervertebral disc spacers in post fusion MRI: Evaluation of the MRI scan quality by using a scoring system-an in vitro study. Neuroradiology 2007;49:103–109. 12. Cutler AR, Siddiqui S, Avinash L M, Hillard VH, Cerabona F, Das K. Comparison of polyetheretherketone cages with femoral cortical bone allograft as a single-piece interbody spacer in transforaminal lumbar interbody fusion. J Neurosurg Spine 2006;5:534–539. 13. Diez-Pascual AM, Naffakh M, Marco C, Ellis G, Gomez-Fatou MA. High-performance nanocomposites based on polyetherketones. Prog Mater Sci 2012;57:1106–1190. 14. Tang S, Cheang P, AbuBakar M, Khor K, Liao K. Tension–tension fatigue behavior of hydroxyapatite reinforced polyetheretherketone composites. Int J Fat 2004;26:49–57. 15. Kane RJ, Converse GL, Roeder RK. Effects of the reinforcement morphology on the fatigue properties of hydroxyapatite reinforced polymers J Mech Behav Biomed 2008;1:261–268. 16. Roeder RK, Smith SM, Conrad TL, Yanchak NJ, Merrill CH, Converse GL. Porous and bioactive PEEK implants for interbody spinal fusion. Adv Mater Process 2009;167:46–48.
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17. Bakar A, Cheang P, Khor K. Mechanical properties of injection molded hydroxyapatite-polyetheretherketone biocomposites. Comp Sci Technol 2003;63:421–425. 18. Hengky C, Kelsen B, Cheang P. Mechanical and biological characterization of pressureless sintered hydroxapatite-polyetheretherketone biocomposite. ICBME 2008, Singapore, 2009, Vol. 23. pp 261–264. 19. Williams D, McNamara A, Turner R. Potential of polyetheretherketone (PEEK) and carbon-fibre-reinforced PEEK in medical applications. J Mater Sci Lett 1987;6:188–190. 20. Ma R, Weng L, Fang L, Luo Z, Song S. Structure and mechanical performance of in situ synthesized hydroxyapatite/polyetheretherketone nanocomposite materials. J Sol gel Sci Technol 2012;62: 52–56. 21. Long M, Rack H. Titanium alloys in total joint replacement—A materials science perspective. Biomaterials 1998;19:1621–1639. 22. Jung HD, Yook SW, Jang TS, Li Y, Kim HE, Koh YH. Dynamic freeze casting for the production of porous titanium (Ti) scaffolds. Mater Sci Eng C 2013;33:59–63. 23. Sarasua J, Remiro P, Pouyet J. The mechanical behaviour of PEEK short fibre composites. J Mater Sci 1995;30:3501–3508. 24. Ferguson SJ, Visser JMA, Polikeit A. The long-term mechanical integrity of non-reinforced PEEK-OPTIMA polymer for demanding spinal applications: Experimental and finite-element analysis. Eur Spine J 2006;15:149–156. 25. Converse GL, Yue W, Roeder RK. Processing and tensile properties of hydroxyapatite-whisker-reinforced polyetheretherketone. Biomaterials 2007;28:927–935. 26. Ashman R, Cowin S, Van Buskirk W, Rice J. A continuous wave technique for the measurement of the elastic properties of cortical bone. J Biomech 1984;17:349–361. [PMC][6736070] 27. Yaszemski MJ, Payne RG, Hayes WC, Langer R, Mikos AG. Evolution of bone transplantation: Molecular, cellular and tissue strategies to engineer human bone. Biomaterials 1996;17:175– 185. 28. Rho JY, Kuhn-Spearing L, Zioupos P. Mechanical properties and the hierarchical structure of bone. Med Eng Phys 1998;20:92– 102. 29. Roeder RK, Sproul MM, Turner CH. Hydroxyapatite whiskers provide improved mechanical properties in reinforced polymer composites. J Biomed Mater Res A 2003;67:801–812. 30. Wu X, Liu X, Wei J, Ma J, Deng F, Wei S. Nano-TiO2/PEEK bioactive composite as a bone substitute material: In vitro and in vivo studies. Int J Nanomed 2012;7:1215–1225. 31. Olivares-Navarrete R, Gittens RA, Schneider JM, Hyzy SL, Haithcock DA, Ullrich PF, Schwartz Z, Boyan BD. Osteoblasts exhibit a more differentiated phenotype and increased bone morphogenetic protein production on titanium alloy substrates than on poly-ether-ether-ketone. Spine J 2012;12:265–272.
TI AS REINFORCEMENT IN PEEK FOR IMPROVED MECHANICAL AND BIOLOGICAL PROPERTIES
