Biomechanical and bioactivity concepts of polyetheretherketone composites for use in orthopedic implants-a review.

Review Article

Biomechanical and bioactivity concepts of polyetheretherketone composites for use in orthopaedic implants - a review Mohamed Ruslan Abdullah1,a, Amirhossein Goharian2, 5, b*, Mohammed Rafiq Abdul Kadir2, 3,c, Mat Uzir Wahit4,d 1

Centre for Composites, Universiti Teknologi Malaysia, 81310 Johor Bahru, Malaysia Medical Devices & Technology Group, Universiti Teknologi Malaysia, 81310 Johor Bahru, Malaysia 3 Department of Biomechanics & Biomedical Materials, Faculty of Biomedical Engineering and Health Science, Universiti Teknologi Malaysia, 81310 Johor Bahru, Malaysia 4 Polymer Engineering Department, Faculty of Chemical Engineering, Universiti Teknologi Malaysia, 81310 Johor Bahru, Malaysia 5 R&D Department, Leonix Sdn. Bhd., 11960 Penang, Malaysia

2

a

[email protected] [email protected] c [email protected] d [email protected] b

* Corresponding author: Medical Devices & Technology Group, Faculty of Biomedical Engineering and Health Science, Universiti Teknologi Malaysia, Johor, Malaysia. Tel.: +(60)17-7091275. Email: [email protected]

Abstract The use of Polyetheretherketone (PEEK) composites in the trauma plating system, total replacement implants, and tissue scaffolds has found great interest among researchers. In recent years (2008 afterward), this type of composites has been examined for suitability as substitute material over stainless steel, titanium alloys, ultra high molecular weight polyethylene (UHMWPE), or even biodegradable materials in orthopaedic implant applications. Biomechanical and bioactivity concepts were contemplated for development of PEEK orthopaedic implants and a few primary clinical studies reported the clinical outcomes of PEEK-based orthopaedic implants. This study aims to review and discuss the recent concepts and contribute further concepts in terms of biomechanical and bioactivity challenges for development of PEEK and PEEK composites in orthopaedic implants. Keywords: Polyetheretherketone, biomechanical, bioactivity, orthopaedic implants

This article has been accepted for publication and undergone full peer review but has not been through the copyediting, typesetting, pagination and proofreading process which may lead to differences between this version and the Version of Record. Please cite this article as an ‘Accepted Article’, doi: 10.1002/jbm.a.35480 This article is protected by copyright. All rights reserved.

Journal of Biomedical Materials Research: Part A

Contents 1.

INTRODUCTION .......................................................................................................................... 2

2.

BIOMECHANICAL CONCEPTS .................................................................................................. 3

3.

2.1

Mechanical stability & stress shielding................................................................................... 3

2.2

Wear ........................................................................................................................................ 5

BIOACTIVITY CONCEPTS ......................................................................................................... 7 3.1

4.

5.

6.

Bioactive coating of PEEK ..................................................................................................... 7

PEEK ORTHOPAEDIC IMPLANTS .......................................................................................... 10 4.1

PEEK in bioactive implants .................................................................................................. 10

4.2

PEEK in spine implants ........................................................................................................ 13

4.3

PEEK in trauma and joint implants....................................................................................... 14

BIOACTIVITY AND BIOMECHANICAL CONCEPTS FOR FURTHER STUDIES .............. 17 5.1

Spinal implant ....................................................................................................................... 17

5.2

Joint implants ........................................................................................................................ 17

5.3

Trauma implants ................................................................................................................... 18

CONCLUSION ............................................................................................................................. 21

ACKNOWLEDGEMENT .................................................................................................................... 22 CONFLICT OF INTEREST and ETHICAL APPROVAL .................................................................. 22 References ............................................................................................................................................. 22

1. INTRODUCTION Polyetheretherketone (PEEK) polymer has been introduced as a candidate material to be utilized for substitution of metals in orthopaedic implants. The PEEK composites were proposed as an advanced biomaterial to treat the trauma, arthroplasty, or tissue loss injuries [1, 2]. The PEEK composite materials have been biomechanically tested and the strength of these materials has been assessed to use in load-bearing implants [3]. For instance, superior radiography properties, wear resistance, and fatigue strength of the carbon fiber reinforced polyetheretherketone (CFRPEEK) have been extensively addressed [3, 4]. The Young's modulus of implant materials has a crucial role in extent of stress shielding. PEEK polymer has a lower modulus compared to metallic implants and its composites could be designed to 2 John Wiley & Sons, Inc. This article is protected by copyright. All rights reserved.

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have a modulus close to that of cortical bone [5]. The related published papers in the area of PEEK and PEEK composites are extensive. In terms of development, biomechanical and bioactivity concepts were used to examine the PEEK and PEEK composites for use in orthopaedic implants. Table 1 shows the progression of the biomechanical and bioactivity studies since 2008 and a significant increase could be observed after 2012. The concepts of biomechanical and bioactivity of PEEK composites for use in orthopaedic implants have been reviewed in this study. Section 2 reviews the selected studies which explore the essential biomechanical concepts of PEEK or PEEK composites for use in orthopaedic implants. The selected studies for bioactivity concepts are then scrutinized in Section 3 to study the perfromance of the PEEK bioactivity for use in orthopaedic implants. In Section 4 the applications of PEEK or PEEK composites in orthopaedic implants (trauma fixation implants, bioactive implants, and total joint replacement implants, and spinal implants) are appraised with respect to biomechanical and bioactivity concepts. In this section some primary clinical outcomes have been also addressed for the PEEK-based orthopaedic implants. Section 5 discusses the challenges and concepts which might be investigated in further researches in order to use the PEEK material in the orthopaedic implants. 2. BIOMECHANICAL CONCEPTS 2.1 Mechanical stability & stress shielding Mechanical stability and physiological stress are the factors that influence fracture healing and joint reconstruction in trauma and total replacement implants respectively. According to Wolff's law [6], the bone counteracts the effects of over-loading and load-shielding (stress shielding). In trauma fractures, stress shielding causes the reduction of physiological stress on the fracture site and therefore, the healed bone strength is not as strong as natural bone. In other words, the cortical bone would not be formed as thick as healthy cortical bone. By 3 John Wiley & Sons, Inc. This article is protected by copyright. All rights reserved.


removing the trauma implant, the healed bone will be stimulated to be more compact and stronger. On the other hand, the stability of the fracture site is crucial for successful fracture healing. If stability is not sufficient, the bone could not be formed at the initial stage of fracture healing and nonunion or malunion might be occurred. Therefore, using high stiffness materials such as stainless steel or titanium alloy would result in lower strength of the healed bone, and using low stiffness material such as polymer or polymer composites would result in insufficient fracture stability to initiate bone formation. CFRPEEK (30% wt) composite has a close mechanical strength to the cortical bone and this could minimize the stress shielding effect [7]. Epari et al. [8] highlighted the importance of shear and axial stability of the fracture fixation during the bone healing. According to the Uhthoff’s et al. [9] study, the cortical segment of the healed bone might be thinner than the healthy bone due to stress shielding of the metal implant. Boudeau et al. [10] implanted a 30% CFRPEEK femoral stem to the femur bone and performed finite element analysis (FEA) and experimental testing on the bone-implant construction. They affirmed that the stress distribution of the implanted femur bone was similar to that of natural healthy bone. Therefore, the balance between flexibility and stability is the key to acquire a healed bone with similar strength of the healthy bone. Fig. 1 demonstrates the schematic comparison of mechanical stability at the fracture site and flexibility of the bone-implant construct for various implant materials. Likewise, the relative stress distribution of the implanted bone is compared with healthy bone for various implant materials (Fig. 1). The flexibility and stability of spine implants have been appraised for CFRPEEK and titanium alloy lumbar spine cage. Kim et al. [11] performed compressive test to evaluate the effect of material properties, cage design, and boundary conditions on the compressive stiffness of the spinal cage. They reported that the compressive strength of the CFRPEEK spinal cage is more affected by altering the cage shape and loading conditions compared to 4 John Wiley & Sons, Inc. This article is protected by copyright. All rights reserved.

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the titanium alloy. With CFRPEEK, the flexibility of the spinal cage under compressive loading conditions was enhanced and bone graft osteoinduction was increased. Ponnappan et al. [12] performed compressive bending and torsion tests to evaluate the mechanical behaviour of lumbar fusion rod system. Based on their study, the PEEK rod could provide a more flexible system which enhanced the load-sharing and consequently interbody fusion. They also discovered that the stress at the bone-screw interface was reduced compared to titanium alloy rod. However, the stability of the PEEK rod system has not been proven to be sufficiently stiff compared to titanium alloy rod system. 2.2 Wear CFRPEEK produces lower wear debris compared to ultra high molecular weight polyethylene (UHMWPE) [13]. Wang et al. [14] indicated the lower wear rate of 30% pitch based CFRPEEK against zirconia femoral head compared to UHMWPE-Zirconia articulation. The suitability of CFRPEEK for total hip replacement (low-stress conforming contact conditions) and non suitability for total knee replacement (high-stress nonconforming contact conditions) were reported in Wang’s et al. [14] study. The intensities of contact condition and contact stress are related to the geometry, loading, and boundary conditions. Wang et al. [15] asserted that the contact conditions are crucial in wear rate of the orthopaedic implants. Therefore, the normal wear tests (e.g. pin on disk) which utilize PEEK or CFRPEEK non-orthopaedic samples (samples that are not in orthopaedic implant design) could not be sufficient even for comparison purposes. Scholes et al. [16] proponed the potential articulation of alumina-CFRPEEK as total hip replacement. They found the low wear rate of CFRPEEK-CoCrMo alloy (cobalt-chromiummolybdenum alloy) used in acetabular cup - femoral head articulation [17]. Xin et al. [18] assessed the wear performance of the cervical disc replacement using spine simulator. The test loading conditions were compressive load and the associated motions complied with ISO 5 John Wiley & Sons, Inc. This article is protected by copyright. All rights reserved.


18192-1. The wear rate has been reported as 1.07 mm3/million cycles (mm3/Mc) [19] and 3 mm3/Mc [20] for a combination of UHMWPE and CoCrMo alloy. Kraft et al. [21] assessed the PEEK-based total disc replacement (TDR) and concluded that the volumetric wear rate in PEEK-PEEK cervical TDR is more than that of UHMWPE-CoCr articulation (the loading and boundary conditions were similar but the design shape was different from Ref. [20]). Wang et al. [22] reported the wear rate of 0.243 ± 0.031 mm3/Mc for articulation of zirconiatoughened-alumina (ZTA) head and a pitch-based CFRPEEK cup. Evans et al. [23] corroborated that the CFRPEEK wear rate was increased for contact stress of more than 6 MPa. In contrast, the wear rate of UHMWPE was decreased by enhancing the contact stress which was also shown in Evans's et al. [23] investigation. Therefore, due to the non-conforming contact conditions between femoral and tibial insert in total knee replacement (TKR), the contact stress could be as high as 17 MPa [24] which makes it a challenge to utilize the CFRPEEK component as the tibial insert component. It is worth mentioning that, non-conforming contact condition occurs when two articulation components are dissimilar in contact surfaces and touch each other along a line which results in concentration of the stress at the small contact area. The contact condition in total hip replacement (TKR) conforms to contact conditions between acetabular cup and femoral head components where the articulation components are touching in multiple areas [25]. Excessive wear rate for contact stress of over 6 MPa might be related to the interfacial strength between carbon fibres and PEEK matrix which is not sufficiently strong to tolerate the high contact stress. Sharma et al. [26] reported the improvement of CFRPEEK wear performance by plasma treatment of the adhesion area between carbon fibre and PEEK matrix. The PEEK polymer typically introduces a transfer film when in contact with metallic components by which the polymer is protected from abrasive wear by the harder metal counterface. Zhang et al. [27] showed that the generated transfer film is changed to the plastic flow for contact 6 John Wiley & Sons, Inc. This article is protected by copyright. All rights reserved.

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stress of over 4 MPa. Laux et al. [28] discovered that the high molecular PEEK could make a thick transfer film at the contact points and protect the wear increment at high contact stress. The smooth surface morphology of PEEK polymer was found to be another factor that influenced the enhancement of the wear rate at high contact stress in Laux's et al. [28] scrutiny. Fig. 2 displays the factors that could enhance the wear resistance of the CFRPEEK composite. UHMWPE has been used as the bearing component in hip, knee, shoulder, and elbow replacement prosthesis. Most of the studies revealed the lower wear rate of CFRPEEK compared to UHMWPE. However, the UHMWPE has undergone improvement so that it can be more wear resistance as the bearing component in joint implants [29, 30]. Reynolds et al. [31] attained the wear rate of 0.037 mm/Mc in clinical study of cross-linked UHMWPE acetabular cup liner against of titanium femoral head. In their research the mean wear rate of 0.054 mm/Mc was reported for a total of 449 patients (from 14 clinical studies) where the commercial cross-linked UHMWPE acetabular cup liners were utilized against titanium femoral component in total hip replacement. Reynolds et al. [31] concluded that the highly cross-linked polyethylene could retain its wear rate in 9 years. Laurent et al. [32] demonstrated the lower wear rate of cross-linked UHMWPE against alumina and CoCr compared to zirconia and lower rate of conventional UHMWPE against zirconia compared to CoCr and alumina. The biomechanical outcomes for the reviewed PEEK implants are given in Table 2. 3. BIOACTIVITY CONCEPTS 3.1 Bioactive coating of PEEK Nakahara et al. [33, 34] developed a hip implant comprising of CFRPEEK acetabular cup, CFRPEEK femoral stem, and alumina femoral head and implanted to the ovine’s hip. Five CFRPEEK acetabular cups and five femoral stems were arranged in two cementless and 7 John Wiley & Sons, Inc. This article is protected by copyright. All rights reserved.


cemented groups. The cementless cups were coated by hydroxyapatite (HA). No stress shielding was observed in both groups. The cementless femoral stems were appropriately integrated to the bone, but the osteointegration of acetabular cups were not successfully obtained in both groups. However, two cementless acetabular cups indicated the bone fixation of acetabular cup. In total, they concluded the successful usage of CFRPEEK in hip implant. In other appraisal by Nakahara et al. [35], the interfacial strength of coated and uncoated CFRPEEK and titanium alloy implants were examined by using the pullout test in the rabbit femur bone. It was shown that the interfacial shear stress of coated CFRPEEK and coated titanium alloy were closed after 6 and 12 weeks of implantation. The similar response to the human osteoblast was achieved in the Sagomonyants's et al. [36] assessment for uncoated titanium alloy and PEEK samples after 2 weeks. However, the interfacial shear strength for uncoated CFRPEEK implant was significantly lower compared to the coated implant. The interfacial shear strength for uncoated titanium alloy kept increasing with time. In order to increase the osteointegration of the PEEK, the plasma immersion ion implantation was utilized by Awaja et al. [37]. In their assessment, the oxygen rich nanofilm was deposited on the surface of PEEK to enhance the surface energy which increased the cell adhesion and protein absorption of the PEEK surface. The proposed process improved the cell adhesion up to 75%. Zhao et al. [38] proposed the sulfonation and subsequent water immersion method to produce a porous layer on PEEK substrate which has enhanced the osteointegration of the PEEK by integration of the bone cells in to the porous layer at the surface of PEEK material. Devine et al. [39] coated the titanium (Ti) on the CFRPEEK screws using vacuum plasma spraying (VPS) and physical vapor deposition (PVD) methods. The uncoated and coated screws were implanted to the sheep’s tibia bone. The results corroborated that the torque removal was higher for VPS coated screws (4.9 ± 1.4 N.m) compared to the PVD coated screws (3.4 ± 0.8 N.m). The shear adhesive strength of VPS coating of the titanium on the

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CFRPEEK has been reported at 29.7 ± 6.5 MPa [40]. The advantage of the VPS method compared to the PVD method was the melting of the CFRPEEK surface which enhanced the deposition of the Ti coated layer to the CFRPEEK. In plasma spraying method, due to the non-uniform characteristics of the coated layer and the possible distortion of substrate under high temperature of plasma, the sputter coating has been proposed for coating of HA on orthopaedic implants [41, 42]. Rabiei et al. [43] utilized the radio-frequency magnetron sputtering (classified as the physical vapor deposition coating method) for coating of HA on PEEK substrate and then used microwave heat treatment method to convert the amorphous HA coating to the crystalline HA. The intermediate layer of yttria-stabilized zirconia (YSZ) was coated before coating of HA since YSZ forms a crystalline coating layer via sputter coating method. The coating of calcium phosphate based materials has been extensively used to enhance the bioactivity of bioinert orthopaedic implants [44]. The amorphous phase of the coating layer could enhance the early osteointegration while the crystalline phase could prevent resorption or dissolution of the coating layer in the body fluid [44]. In one recent study by Ma et al. [45], the 45 wt.% HAPEEK was modified by silane coupling agent (KH560) and coated on the PEEK substrate to enhance the bioactivity of the PEEK material. Ma et al. [45] achieved that the adhesion of modified HAPEEK to the PEEK was improved compared to the normal HAPEEK. Lee et al. [46] utilized cold spray method to coat HA on PEEK substrate. The HA coated and uncoated cylinder samples were inserted to the rabbit's illium. Tensile test was performed to pull out the implanted screws after 8 weeks of the implantation. The tensile force of 193 ± 94.5 N was attained in HA coated cylinders which were significantly higher than that of uncoated cylinders (18.5 ± 14.1 N). Zhou et al. [47] exposed the PEEK surface to a microwave irradiated concentrated biomimetic fluid. The PEEK samples were etched in NaOH (sodium hydroxide) solution to enhance the formation of apatite layer on the surface. 9 John Wiley & Sons, Inc. This article is protected by copyright. All rights reserved.


The results proved that the deposited coating layer was cytocompatible and bioactive. Titanium ions (TiO2 nanoparticles) were coated to the CFRPEEK substrate by plasma immersion ion implantation in the study of Lu et al. [48]. The advantage of this method was the formation of nanoporous multilevel TiO2 coating layer which has enhanced the antibacterial resistance of the CFRPEEK against staphylococcus aureus and escherichia coli. Hahn et al. [49] has coated HA on the PEEK substrate using aerosol deposition method. No thermal degradation of PEEK substrate was observed. Then the HA coated layer was hydrothermally annealed to promote the crystalline portion of the coating layer. Han et al. [50] has also proposed the electron beam deposition method for coating of pure titanium on the PEEK substrate. Improved osteointegration has been reported for the Ti-coated substrates. In addition of bioactivity intensification, the HA coating could improve the biocompatibility of PEEK/Magnesium composite [51]. Table 3 represents the in-vitro and in-vivo bioactivity tests that have been utilized to evaluate the osteointegration of the coated PEEK substrates in the reviewed papers. 4. PEEK ORTHOPAEDIC IMPLANTS 4.1 PEEK in bioactive implants Due to the physical strength of the PEEK polymer, its composition with bioactive materials has been used as scaffold for reconstruction of bone tissues. Wilmowsky et al. [52] appraised the bioactivity of the laser sintered PEEK powder compounded with carbon, bioglass, and βtricalcium phosphate (β-TCP). Wilmowsky et al. [52] reported that PEEK-bioglass compound had the highest cell viability and could be efficiently utilized as bone substitute. Tissue engineering scaffolds are normally porous materials to allow the tissue cells to penetrate the scaffold and regenerate the tissue at the suffered area. Currently tissue scaffolds are under study for treatment of tissue loss such as cancellous bone, cartilage, and bone marrow. Tan et al. [53] utilized the rapid prototyping laser sintering process to fabricate 10 John Wiley & Sons, Inc. This article is protected by copyright. All rights reserved.

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bioactive HAPEEK composite scaffold. The process parameters such as scan speed, part bed temperature, and laser power were altered to assess the microstructural arrangement of the scaffold to control the porosity for use as tissue scaffold. There was an interest in compounding PEEK polymer with hydoxylapatite (HA) to achieve a bioactive PEEK composite with good mechanical strength and bioactivity. Ma et al. [54] fabricated the HAPEEK composite with HA contents of 2.6, 5.6, 13.4, and 23.9 vol. %. The in vivo bioactivity tests asserted the continuous bounding of bone tissues to the 6.5 vol. % HAPEEK implant without fibrous tissues after three months implantation. Likewise, Ma et al. [55] obtained the tensile stress of 100 MPa for the 6.5 vol % HAPEEK which is close to that of cortical bone (120 MPa [56]). Therefore, Ma et al. [55] concluded that the 6.5 vol % HAPEEK has the desired bioactivity and mechanical strength for use as load bearing bioactive implant. Wang et al. [57] fabricated the HAPEEK composite in various nano-HA contents of 5, 7.5, and 10 vol %. Nano-HA particles and PEEK powder was compounded via high speed ball mill and then prepared as dumbbell-shaped specimens for tensile test using injection moulding process. The maximum tensile strength of 93 MPa was obtained for 5 vol. %. In further investigation by Wang et al. [58], it was described that by reducing the size of nano-HA particles and further annealing of the injection moulded HAPEEK specimens, the interaction bonding between HA and PEEK was getting stronger and consequently the tensile strength was increased to 98 MPa for 5 vol. % HAPEEK composite. Converse et al. [59] reported the tensile strength of 90 MPa for the compound of PEEK and 10 vol. % HA whiskers. In other perusal, Converse et al. [60] investigated the tissue scaffold made from whiskered HAPEEK composite in various HA contents of 0 to 40 vol. %. The powder processing, compression molding, and particle leaching processes were utilized to e acquire the porosity of 75-90 % which is a desired range for bone in-growth. Yu et al. [61] tested the bioactivity of the HAPEEK composites by SBF test. It was depicted that by 11 John Wiley & Sons, Inc. This article is protected by copyright. All rights reserved.


increasing the content of HA in the HAPEEK composite, the apatite formation on the composite surface was increased which is an indication of enhanced bioactivity. In Wong’s et al. [62] study, the stronium-containing hydroxyapatite (Sr-HA) was proposed for loadbearing orthopaedic implants. The bending strength of the Sr-HAPEEK composite for 25 vol. % has been achieved 93.8 ± 10.3 MPa. Likewise, it was professed that the apatite formation on the composite surface was higher and thicker in Sr-HAPEEK compared to HAPEEK composites. They concluded that the stronium could enhance the mechanical properties of the HAPEEK composite in higher contents of HA up to 25 vol. % while increasing the bioactivity characteristics of the HAPEEK composite. The mechanical properties of the porous whiskered HAPEEK composites have been studied by Converse et al. [63]. The porosity range of 75-90 %, HA volume range of 0-40 %, and mold temperature range of 350-375°C were used to explore the effect of these parameters on yield strength of the porous whiskered HAPEEK composite. It was found that by lowering porosity and increasing mold temperature, the yield strength was increased. The maximum yield strength was attained for the median volume range of HA (20 vol %). The optimum values were achieved with 75% porosity, 20 vol% HA content, and 375°C mold temperature, resulting in the yield strength of 2.2 MPa which was close to that of human vertebral trabecular bone [64-66]. Converse et al. [63] concluded that the fabricated scaffold from porous whiskered HAPEEK could be utilized as bone substitution to regenerate the bone loss at the interbody spinal fusion. Tang et al. [67] developed a 3D finite element (FE) model to predict the mechanical behaviour of porous HAPEEK structure under tensile and compressive stresses by which similar outcomes have been obtained as Converse's et al. [63] study. The yield tensile strength of 2.25 MPa and yield compressive strength of 1.4 MPa were acquired for the 76 % porosity and 20 vol % HA content. Tang et al. [67] also affirmed that by increasing the HA content to 40 vol %, the yield tensile and compressive strength were 12 John Wiley & Sons, Inc. This article is protected by copyright. All rights reserved.

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reduced. Bakar et al. [68] has also achieved the reduction of the tensile strength, tensile strain, and fatigue strength of the HAPEEK composites by increasing the HA content. In a recent published assessment, Xu et al. [69] compounded PEEK polymer with 25 wt.% n-HA (Nano HA) and 15 wt.% carbon fiber (CF) followed by plasma oxygen and sand blasting treatments to obtain a biocomposite for use in bone scaffolds. In addition of bioactivity advantageous, the superior mechanical strength of the achieved PEEK/CF/n-HA composite (due to existence of carbon fibers) could be explored in further researches. 4.2 PEEK in spine implants Spinal fusion cages are hollow cylindrical or square-shaped prosthetics that are placed in between two problematic vertebrae to allow bone growth leading to fusion of the two vertebrae. Kasliwal et al. [70] demonstrated the successful clinical outcomes of the PEEK cage for reconstruction of anterior column of the cervical spine in 35 patients. Chou et al. [71] investigated the clinical performance of the PEEK and titanium cages with bone grafts and bone graft treatment without cage for fusion of anterior cervical in 55 patients. The results showed that after one year, a 100% fusion rate was achieved in PEEK cages with two bone grafts compared to 46.51% fusion rate for titanium cages. The complication rate for patients with bone grafting treatment was 52% while it was 11 % and 40.1 % for PEEK and titanium cages, respectively. The donor site and limb complications were reported in titanium cage and bone graft treatment, respectively, but have not been observed in PEEK cage cases. Sahoo et al. [72] reported good clinical outcomes with no complications for replacement of PEEK cages between the cervical vertebrae. Additional plate was used to maintain the cage at the disc space and prevent the migration of the PEEK cage. Kersten et al. [73] achieved high rate of fusion and good clinical outcomes for cervical PEEK cages. Chang et al. [74] followed up clinical outcomes of the 24 patients who were treated with cervical PEEK cage for one year. Good clinical outcomes have been reported with no implant failure such as cage 13 John Wiley & Sons, Inc. This article is protected by copyright. All rights reserved.


failure, migration, or other complications. In addition, the radiologic measurement parameters (anterior disc height, interbody angle, interbody height) had been similar at immediate post operation and one year of implantation. After one year the fusion rate was 92.6%. Lumbar spinal fusion has been developed with PEEK and titanium materials. Osteointegration of these implants have been under development [75-80]. Micro-scale [75] and nano-scale [76] surface roughening, high porosity surface [77], and HA coating [78] have been utilized to enhance the bioactivity of titanium lumbar spinal fusion implants. Compounding or coating of PEEK with bioactive ceramic materials such as HA, bioglass, and β-tricalcium phosphate [79, 80] increased the bioactivity of the PEEK lumbar spinal fusion implants. Song et al. [81] reported the successful clinical outcomes of 58 patients who were treated using cervical PEEK cage. The bony fusion was observed within three months after implantation with good cage stability. The study by Rivard et al. [82] asserted the harmless effect of the PEEK to the spinal cord and nerve roots by implantation of PEEK spinal implant in New Zealand white rabbits. 4.3 PEEK in trauma and joint implants Latif et al. [83] reported the pre-clinical evaluation of the CFRPEEK acetabular cup in which a lower wear rate for the CFRPEEK/alumina has been observed compared to the UHMWPE/alumina. Field et al. [84] reported the good early osteointegration for CFRPEEK acetabular cup against ceramic femoral head. 25 patients were followed for three years and the improvement of the Oxford hip [85], Harris hip [86, 87], and Euroqol-5D [88] scores have been attained as given in Table 4. Kinbrum et al. [89] reported that the low wear rate of CFRPEEK against CoCrMo alloy had encouraged the usage of CFRPEEK as knee bearing component. They also proposed that since the CFRPEEK had been proven as a load-bearing material [4], the tibial tray could be 14 John Wiley & Sons, Inc. This article is protected by copyright. All rights reserved.

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produced from CFRPEEK with bioactive coating for enhancement of osseointegration [89]. Thus, the tibial bearing and tray components could be an integrated CFRPEEK component rather than UHMWPE for tibial bearing and titanium alloy for tibial tray. However, no clinical study and wear analysis of CoCrMo alloy femoral against CFRPEEK tibial bearing have been reported to examine the wear rate of the proposed integrated knee implant. The good performance of CFRPEEK bearing was shown in total hip and knee implants with high conformity articulation with femoral head and femoral components, respectively [14, 15, 83, 90]. Grupp et al. [91] scrutinized the wear performance of fixed bearing unicompartmental knee implant in which the CoCrMo alloy femoral was used in articulation with UHMWPE, pitch fiber CFRPEEK, and PAN fiber CFRPEEK. The volumetric wear found to be 8.6 ± 2.17, 5.1 ± 2.29, and 5.2 ± 6.92 mm3/Mc for UHMWPE, pitch CFRPPEK, and PAN CFRPEEK bearings, respectively. The pitch carbon fiber reinforced PEEK had a potential to be used in low conformity knee fixed implant. Grupp et al. [91] concluded that the usage of CFRPEEK in fixed bearing unicompartmental knee implant with low congruency could not be suitable. 30 % CFRPEEK was used as the lateral femoral flange and bushing for rotation axis in a new proposed rotating hinge knee implant. Grupp et al. [92] utilized this knee implant to evaluate the wear rate of CFRPEEK against of CoCrMo alloy with and without the coating of multilayered ZrN. CFRPEEK/CoCrMo articulations demonstrated superior wear factors compared to polyethylene/CoCrMo [17]. The PVD coating of multi-layered ZrN had enhanced the wear resistance of the CoCrMo femoral on UHMWPE tibial insert [93] by which the volumetric wear rate was 2.3 ± 0.48 and 0.21 ± 0.02 mm3/Mc for articulation of CFRPEEK with noncoated and coated CoCrMo alloy, respectively. Tarallo et al. [94, 95] reported the successful usage of CFRPEEK volar distal radius plate in a clinical study on 50 cases for a duration of 15 months. Fracture types of 23-C and 23-B (based on the arbeitsgemeinschaft fur 15 John Wiley & Sons, Inc. This article is protected by copyright. All rights reserved.


osteosynthesefragen (AO) classification [96]) were investigated in Tarallo’s et al. [94, 95] study. DASH (disabilities of the arm, shoulder, and hand) score was achieved as 6.0 whilst the average grip strength was 92 %. No plate breakage or screw lessening was observed and all fractures were healed in an average of 6 weeks. Steinberg et al. [97] appraised CFRPEEK tibial nail, dynamic compression plate, proximal humeral plate, and distal radius volar plate by using four-point bending, static torsion (nail), bending fatigue, and wear tests. Steinberg’s et al. [97] study revealed that the CFRPEEK implants have similar mechanical performance as titanium implants. However, biomechanical evaluation with consideration of human loading and boundary conditions was essential when examining the CFRPEEK trauma implants. Feerick et al. [98] assessed the advantage of the CFRPEEK locking plate and intramedullarly nail for fracture fixation of proximal humerus. It was observed that the CFRPEEK implants could significantly reduce the stress concentration at the implant-anchor screw interface compared to the metal and this decreased the risk of screw pullout/pushout. Also the CFRPEEK implant introduced fewer side effects on the stability of bone-implant construction compared to the titanium implant. Budassi et al. [99] investigated the clinical outcomes of the PEEK proximal humerus plate and titanium alloy screws for fixation of proximal humerus fractures. In their study, ten patients with the average age of 70 years were followed up. The percentages of union and functional outcomes have been obtained similar to the titanium alloy implant. Furthermore, the PEEK plate could remove the potential effect of galvanic corrosion between the plate and screw. Maniscalco et al. [100] used CFRPEEK in the proximal portion of the intramedullary nail for fracture fixation of proximal tibia fractures. It was observed that the angular stability of the proximal screws was enhanced thereby no pull-out or migration of proximal screws occurred. Rohner et al. [101] evaluated the performance of 62% CFRPEEK locking compression plate for fracture fixation of sheep's tibia and compared it with titanium alloy plate. The successful union was acquired for both


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plates with similar healed bone strength and callus dimensions. The advantage of CFRPEEK was reported to be higher deformation resistance compared to titanium alloy. The summary of using PEEK & CFRPEEK in orthopaedic implants is given in Table 5. 5. BIOACTIVITY AND BIOMECHANICAL CONCEPTS FOR FURTHER STUDIES

The biomechanical and bioactivity concepts of using PEEK and PEEK composites for orthopaedic implants have been reviewed. Based on the reviewed articles, the biomechanical concepts had been used to evaluate the mechanical strength and flexibility of the PEEK orthopaedic implants. Likewise, the bioactivity concepts had been scrutinized to improve or optimize the osteointegration of the orthopaedic implants. Following these, other biomechanical and bioactivity concepts that could be considered in development of the PEEK and PEEK composites are discussed. 5.1 Spinal implant PEEK has been clinically used in spine implant as cage to support the cervical and lumbar vertebrae with a good clinical and biomechanical outcomes (refer to section 4.2). High cyclic fatigue study with human physiological loading and boundary conditions could be contemplated in developing PEEK and PEEK composites for spine cage. 5.2 Joint implants One of the potential usages of CFRPEEK composite is total hip and knee replacements (THR and TKR). The PEEK composite (e.g. CFRPEEK) was proposed for tibial insert in TKR and acetabular cup in THR (Table 5). The main challenge has been the wear rate of the CFRPEEK bearing component in THR and TKR which has been reviewed in section 2.2. In addition, the surface hardness of the CFRPEEK composite could also be investigated in further researches to reduce the wear rate. Motion analysis of TKR and THR (analysis of the force-displacement and torque-rotation for the articulation components in 5 translation and



rotation axes) has not been studied for the CFRPEEK and associated articulation component. Based on ASTM F1223 standard or relevant published studies [102, 103], the kinematic constraints of the total joint replacements should be tested and adopted with natural constraints of the joints. This probably influences the geometry of the joint implant at the interface and consequently, affects the conformity contact condition which is an important parameter in intensity of the wear rate. Therefore, the wear and kinematic analyses might be investigated together in the development of CFRPEEK for total joint replacement implants. The PEEK composite (e.g. CFRPEEK) was also proposed for integrated tibial insert and tray in TKR (Table 5). The strength as well as the osteointegration to the tibia bone would be future challenges of this proposed PEEK integrated tibial component. Recently, the authors explored the combination of bioinert non-degradable (30% chopped CFRPEEK), bioactive non-degradable (20% HAPEEK), and bioactive degradable (HA) composite for use in acetabular cup [104]. The same concept could be contemplated for tibial component in TKR to obtain a PEEK composite with superior wear, strength, and osteintegration characteristics. The majority of the researches in section 3.2 have assessed and developed the coating processes for enhancement of the PEEK implant bioactivity. Superior bioactivity results could be observed in all such investigations, but the important thing is the bonding strength of the coated material with the substrate. The adhesion strength of the bioactive coated material on the PEEK component is essential to be investigated for use of more than 10 years after implant replacement. The coating layer strength should have sufficient strength and deposition to the implant. 5.3 Trauma implants CFRPEEK implant bears lower stress due to the lower Young’s modulus compared to the metal implants (titanium alloy or stainless steel) at similar strain and therefore more stress is transformed to the bone, resulting in normal physiological loading conditions on the bone. 18 John Wiley & Sons, Inc. This article is protected by copyright. All rights reserved.

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The Young’s modulus of the 30% CFRPEEK is close to that of cortical bone and could acts as the supportive cortical bone structure for fracture healing. In this regard, some trauma plates have been made with 30% CFRPEEK with the same design as commercial titanium alloy plates. The lack of researches (FE analysis or experimental testing) for modification of CFRPEEK design proposes a wide range of investigations for development of the CFRPEEK trauma implants. In the locking compression plating system, it is crucial to provide a smooth locking of the screw into the plate. Due to the higher wear resistance of CFRPEEK compared to the metallic material, a smoother locking could be predicted using CFRPEEK screw or plate. The hardness of metals surface could be modified significantly in producing a good strength in sharp edges such as threads. Since the mechanical properties of the CFRPEEK are much lower than metals, the strength of thread crest may not be enough to withstand the physiological dynamic loading conditions and might be cracked. The delamination between fibre and matrix increase the risk of internal crack and crack at the surface compared to metal alloys and pure polymers. The molecular bonding between pure polymers monomers and metal molecules are stronger than fiber and matrix in CFRPEEK. However, the locking mechanism has not been evaluated for the CFRPEEK locking plating system, which opens an extensive area to study. Currently, machining is the main fabrication process of metal trauma implants. The machining capability of the CFRPEEK is not as good as metals. This might be due to the isotropic mechanical properties of metals, whereas the CFRPEEK composite is not isotropic [3]. The other issue is osteointegration of the CFRPEEK screws to the bone. Generally, the screw should be integrated with the bone to provide an appropriate fixation of the screws to the bone during fracture healing. Conversely, the integration of the screw to the bone should not be too strong to facilitate the screw removal. Due to the weaker osteintegration of the CFRPEEK compared to titanium alloy [35], it is essential to develop 19 John Wiley & Sons, Inc. This article is protected by copyright. All rights reserved.


and optimize the osteintegration of CFRPEEK surface for appropriate fixation of bone-screw during the fracture healing and easier removal of screw from the bone once the fracture has healed. Some load-bearing implants (e.g distal femur, proximal tibia, distal tibia, proximal femur plates) are under bending stress generated by body weight loading conditions. The anatomical trauma plates are more critical than straight plates under bending moment. Anatomical plates are used to treat the bone fractures at the distal or proximal portion of the long bones and straight plates are utilized to treat the bone fractures at the shaft portion of the long bones. The straight plates are usually fabricated by machining, whereas in anatomical plates, forging or forming processes are recruited additionally by which residual stress is introduced to the plate. Brown et al. [105] corroborated the good thermoforming of the 30% chopped pan CFRPEEK at 250°C, hence no stress is residue in the implant in fabrication of CFRPEEK anatomic trauma implants. Further finite element analysis and biomechanical cyclic testing could be carried out to examine the strength of anatomic and straight PEEK implants for load bearing aspects. The clinical investigations represented a successful union of the trauma fractures using titanium alloy implants. Particularly, the locking compression plate has been recently reported to produce a good internal fixation method for majority of trauma fractures. There was a low rate of implant failure, screw loosening, and loss of reduction with the titanium alloy plating systems [106-129]. The plate for fixation of intraarticular, extraarticular, and multifragmentory fractures at distal radius [106-109], distal femur [110-113], proximal tibia [114-117], one third tabular plate [118-120], reconstruction plate [121-123], distal humerus [124-126], proximal humerus [127, 128], hook plate for olecranon [129] have been used effectively with good clinical outcomes. Titanium has been under development for new compositions of titanium alloys for use in trauma implants [130-132]. Load bearing trauma locking plates are under body weight axial compression loading condition. For instance, the 20 John Wiley & Sons, Inc. This article is protected by copyright. All rights reserved.

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axial stiffness of 1000 ± 200 N/mm [133-136] has been reported for fracture fixation of the proximal tibia metaphyseal fractures using the titanium alloy locking plate. On the other hand, the axial stiffness of the synthetic tibia bone (4th gen. composite tibia, Sawbones, Vashon, USA) has reported 7450 N/mm [137]. Due to the lower Young's modulus of the 30% CFRPEEK compared to the titanium alloy (Fig. 1), much lower stiffness of the bone-plate construction is expected for CFRPEEK locking plates. As stated in section 2.1, high flexibility (low stiffness) of the fracture fixation could enhance the risk of the implant failure or misalignment of the bone fragments. Therefore, the axial stiffness of the bone-implant construction should be investigated further for development of the PEEK composites for load bearing implants. However, the goal of using PEEK composites in trauma implants is to explore a lightweight and flexible implant which could provide the advantages over titanium implants. 6. CONCLUSION Recent published studies revealed the importance of the biomechanical and bioactivity concepts for development of the PEEK orthopaedic implants. In view of biomechanical concepts, the stability and strength of the PEEK implants during the treatment of bone injuries should be assessed more meticulously by considering the constraint of involved soft tissues at the injured site. In this respect, the flexibility of the implant was affirmed to be effective on the strength of the injured bone. Therefore, the balance between flexibility and stability should be contemplated in development of the PEEK implants. The wear resistance of the implant surfaces would also be crucial to appraise. It has been asserted that the extent of contact stress and sliding distance at the interface of articulation influenced the ranges of wear rate. Therefore, the contact conditions are vital to obtain the reliable results from the wear test. In sight of bioactivity concepts, the PEEK composite substrates were coated by various bioactive materials using multiple coating processes and conditions which enhanced 21 John Wiley & Sons, Inc. This article is protected by copyright. All rights reserved.


the bioactivity or osteointegration of PEEK composites. However, the remained challenge in this respect is the bonding strength of the coated layer and PEEK composite during treatment or replacement of the bone injury. The superior mechanical strength of PEEK polymer enhanced the attraction of developing PEEK composites in orthopaedic implants such as trauma implant, joint implant, and bone scaffolds. Lower wear rate and stress shielding in conjunction with higher osteointegration have been the concepts for using of PEEK composite in joint implants. Balanced extent of stability and flexibility were found to be crucial for treatment of trauma fractures using PEEK composite trauma implants. In bioactive PEEK implants, the optimum amount of bioactive material (e.g. HA, bioglass) has asserted to be crucial to obtain a bioactive PEEK composite with adequate mechanical strength and lower brittleness. Although, PEEK or PEEK composites could provide advantageous biomechanical characteristics compared to metals, ceramics, and other polymers, further biomechanical and bioactivity studies are essential in order to utilize PEEK composites in orthopaedic implants. ACKNOWLEDGEMENT We gratefully acknowledge the funding from the Ministry of Science, Technology, and Innovation (MOSTI) Malaysia, under Science Fund Grant Scheme (Vote no. 79375). CONFLICT OF INTEREST and ETHICAL APPROVAL There was no conflict of interest in carrying out this research. In addition, the ethical approval was not required for this study. References 1. Horak Z, Pokorný D, Fulin P, Slouf M, Jahoda D, Sosna A. [Polyetheretherketone (PEEK). Part I: prospects for use in orthopaedics and traumatology]. Acta chirurgiae orthopaedicae et traumatologiae Cechoslovaca. 2009; 77: 463-9. 2. Pokorný D, Fulin P, Slouf M, Jahoda D, Landor I, Sosna A. [Polyetheretherketone (PEEK). Part II: application in clinical practice]. Acta chirurgiae orthopaedicae et traumatologiae Cechoslovaca. 2009; 77: 470-8. 22 John Wiley & Sons, Inc. This article is protected by copyright. All rights reserved.

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List of Figure Captions Fig. 1 Relation of stress distribution on the adjacent bones, mechanical stability of the fracture site, and flexibility of the bone-implant construct to the implant material Fig. 2 Improvement of CFRPEEK composite wear resistance in high stress or non conforming contact condition



Relation of stress distribution on the adjacent bones, mechanical stability of the fracture site, and flexibility of the bone-implant construct to the implant material 206x160mm (300 x 300 DPI)

John Wiley & Sons, Inc. This article is protected by copyright. All rights reserved.

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Improvement of CFRPEEK composite wear resistance in high stress or non conforming contact condition 138x55mm (300 x 300 DPI)



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Table 1 Number of papers related to the PEEK material based on the investigated area 2014 (1st quarter)

2013

2012

2011

2010

2009

2008

Review

1

1

-

1

-

2

-

Clinical

2

3

2

1

1

1

-

Biomechanical

2

11

7

2

4

6

4

Bioactivity

6

8

4

-

4

2

3

Total

11

23

13

4

9

11

7


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Table 2 Biomechanical outcomes for PEEK spine and hip implants Study

Evaluation subject

Material

Type of loading & analysis

Outcomes

Kim et al. [11]

Lumbar spine cage

CFRPEEK & Titanium

Compressive load 1000 N , FEA

CFRPEEK cage is more flexible than Ti

Ponnappan et al. [12]

Lumbar fusion rod

PEEK & Titanium

Compressive bending, torsion, static & dynamic

More flexible PEEK rod system compared to titanium

Wang et al. [14]

Acetabular cup insert Femoral head

CFRPEEKZirconia

Wear analysis using hip simulator ISO 14242-2

Wear rate: 0.0017 mm/Mc Volumetric wear rate: 0.39 * mm3/Mc

Wang et al. [15]


UHMWPEZirconia

Wear analysis using hip simulator

Wear rate: 0.038 mm/Mc

Wang et al. [22]


CFRPEEKZirconia


Volumetric wear rate: 0.243 ± 0.031 mm3/Mc

Scholes et al. [16]


CFRPEEKAlumina


Volumetric wear rate: 1.16 mm3/Mc

Essner et al. [29]


XLPE-Alumina



Xin et al. [18]

Cervical disc replacement

PEEK-PEEK

Wear analysis using spine simulator

Volumetric wear rate: 0.7 ± 0.7 mm3/Mc

Reynolds et al. [31]


Cross-linked UHMWPETitanium

Clinical study

Wear rate: 0.037 mm/Mc

Laurent et al. [32]


Cross-linked UHMWPEZirconia, Alumina, CoCr


Volumetric wear rate: < 0.54 mm3/Mc

Bracket et al. [30]


CFRPEEKZirconia-alumina reinforced



*

Mc = million cycles



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Table 3 Bioactivity tests of the coated PEEK substrates in reviewed articles in section 3.2 Study

In vitro bioactivity tests

In vivo bioactivity tests

Wilmowsky et al.

Cell culture- human osteoblast (hFOB 1.19) Cell morphology using SEM Cell viability using FDA & PI Cell Proliferation using labeling kit WST-1 (at 3, 7, 14 days)

Wong et al.

[52]

Biocompatibility test :HAPEEK powder Acute toxicity test (rat - 7days) Hemolytic test (rabbit) Sensitization (rat - 24,48, 72 h) Pyrogen test (rabbit - 24, 48, 72 h) Intradermal test (rabbit -24, 48, 72 h) Toxicity assay test on tissues and cells (injected to abdominal cavity of rat - one week) In vivo bioactivity (insert implant in femur rat - 1,2,3 months)

Ma et al.

Osteoblast proliferation, alkaline phosphate activity, and mineralization activity using osteoblast-like cell line (MG-63)

Awaja et al.

Cell attachment analysis test using MG63 cells on PEEK samples

Zhao et al.

Cell adhesion test by seeding the mouse MC3T3-E1 pre-osteoblast on 3D porous network on PEEK surface, Cell viability and cell proliferation using (MTT) Assay to determine the viable MC3T3-E1 cells Cell apoptosis test Osteogenic gene expression

[53]

[54]

Implantation of CFRPPEK acetabular cup and femoral stem in sheep

Nakahara et al.

Ref.

[33, 34]

[37]

Implantation of SPEEK-WA,SPEEK-W, AND PEEK cylindrical samples in distal femur of rat

[38]

Devine et al.

Implantation of CFRPEEK custom plate in Sheep

[39]

Wieling et al.

Implantation of CFRPEEK screw in diaphyseal cortical bone of the sheep

[40]

Rabiei et al.

Cell adhesion and cell proliferation test using human fetal osteoblast cell line CRL 1486 human embryonic palatal mesenchyme (HEPM) cells

Lee et al.

Cell adhesion using human bone marrow mesenchymal stem cells (hBMSCs) on PEEK and HA-coated PEEK disks Cell viability test using MTS assay ALP assay

[43]

Implantation of PEEK and HA-coated PEEK cylindrical bar sample in rabbit's ilium


[46]

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Calcium assay for osteoblast differentiation DNA test Zhou et al.

Cytocompatibility test using MC3T3-E1 preosteoblast cells on PEEK-coated samples

Hahn et al.

Biological response, Cell proliferation, cell differentiation using MC3T3-E1 preosteoblast cells (PEEK with and without HA coating)

Implantation of PEEK and HA-coted PEEK screw-shaped implant in rabbit, helaing period 4 weeks to see the outcomes for osteointegration

[49]

Han et al.

Biological properties included cell attachment, proliferation, differentiation using MC3T3-E1 cell line

Implantation of PEEK and Ti-coated PEEK screw-shaped implant in rabbit, healing period 4 weeks to see the outcomes for osteointegration

[50]

[47]

SEM=Scanning electron microscopy, FDA=Fluoresceine diacetate, PI=Propidium iodide, MTT= Methylthiazol Tetrazolium,



Page 38 of 40

Table 4 Pain and functional scores for three years clinical investigation of CFRPEEK acetabular cup Score method

Score grading

Score preoperatively

Score after three years follow-up

Oxford Hip score [85]

0-19 severe hip arthritis 20-29 moderate to severe hip arthritis 30-39 mild to moderate hip arthritis 40-48 satisfactory joint function

19.6 ± 7.5

43.5 ± 7

Harris hip score [86, 87]

In vitro biocompatibility of polyetheretherketone and polysulfone composites.

Incorporating population-level variability in orthopedic biomechanical analysis: a review.

Preparation Methods for Improving PEEK's Bioactivity for Orthopedic and Dental Application: A Review.

Enhancing orthopedic implant bioactivity: refining the nanotopography.

Preparation, characterization, in vitro bioactivity, and cellular responses to a polyetheretherketone bioactive composite containing nanocalcium silicate for bone repair.

Porous silicon confers bioactivity to polycaprolactone composites in vitro.

Current Concepts in Orthopedic Management of Multiple Trauma.

Evidences of in vivo bioactivity of Fe-bioceramic composites for temporary bone implants.

polyetheretherketone biocomposite as orthopedic implant material.

iPhone and iPad Use in Orthopedic Surgery.

gold composites.

Polyetheretherketone custom-made implants for craniofacial defects: Report of 14 cases and review of the literature.

Use of Computer Navigation in Orthopedic Oncology.

Polyetheretherketone (PEEK) cages in cervical applications: a systematic review.

A high-modulus polymer for porous orthopedic implants: biomechanical compatibility of porous implants.

Fabrication and characterization of polymer composites for endodontic use.

Use of bone marrow derived stem cells in trauma and orthopaedics: A review of current concepts.

The Use of Carbon-Fiber-Reinforced (CFR) PEEK Material in Orthopedic Implants: A Systematic Review.

Durability and integrity studies of environmentally conditioned interfaces in fibrous polymeric composites: critical concepts and comments.

Use of bisphosphonates in orthopedic surgery: pearls and pitfalls.

Development of a degradable composite for orthopaedic use: in vivo biomechanical and histological evaluation of two bioactive degradable composites based on the polyhydroxybutyrate polymer.

Cyclopolymerizable monomers for use in dental resin composites.

Biomechanical and clinical changes of the craniofacial complex from orthopedic maxillary protraction.

Graphene and Polymer Composites for Supercapacitor Applications: a Review.