Table 3.

(A) Biomechanical studies and (B) clinical studies that examined CFR-PEEK as an implant material.

(A) FIRST AUTHOR (YEAR)	LOCATION	MATERIALS ASSESSED	TESTS USED	RESULTS OF THE TEST (TECHNICAL DATA)	SAFETY (CONCLUSION)	OUTCOME
Brown, SA (1990)	North America	CFR-PEEK PAN thermoplastic for fracture fixation devices, compared to polysulphone and polybutylene terephthalate.	Flexion tests Fracture toughness testing	CFR-PEEK material showed no degradation in mechanical properties after contouring and saline soaking.	The CFR-PEEK PAN composite was easiest to contour and had the best mechanical properties. Preliminary biocompatibility test results have been encouraging and the CFR-PEEK PAN composite is an excellent candidate for further study for such applications.	(+)
Jockish, KA (1992)	North America	CFR-PEEK fracture fixation plate, compared to UHMWPE and PEEK.	Muscle implant testing In vivo functional compatibility testing	Normal muscle tissue with no signs of infection or an adverse tissue response. Very few inflammatory cells present in the tissue surrounding any of the implant materials. PEEK and CFR-PEEK implants showed similar tissue response to UHMWPE. No difference in callus response and soft tissue healing.	Animal subjects remained very active and the plates did not fail mechanically. CFR-PEEK particles were well tolerated by the subjects. CFR-PEEK plates were mechanically capable of supporting a fracture, even under adverse conditions.	(+)
Scholes, SC (2007)	United Kingdom	(Pin material + Plate material) 1. CFR-PEEK-OPTIMA® PAN +BioLox Delta 2. CFR-PEEK-OPTIMA® pitch + BioLox Delta 3. CFR-PEEK-OPTIMA® PAN + BioLox Forte 4. CFR-PEEK-OPTIMA® pitch + BioLox Forte	Multidirectional pin-on-plate machine	The BioLox Delta plates seem to wear slightly less than the BioLox Forte plates when artic ulating against the same CFR-PEEK-OPTIMA® pin material. The difference is statistically significant for both the PAN and pitch pins (P < 0.05). No statistically significant difference in the total wear for each material combination (ANOVA P > 0.20). The CFR-PEEK-OPTIMA® pitch pins seem to perform the best when articulating against BioLox Forte.	CFR-PEEK-OPTIMA® articulating against ceramic has been found to give low wear factors compared to metal-on-metal samples. This material combination may perform well in joint applications.	(+)
Latif, AMH (2008)	United Kingdom	CFR-PEEK acetabular cup	Finite Element Analysis Wear studies using hip joint wear simulator Biocompatibility tests Mechanical tests Stability tests	Results show that CFR-PEEK cups are comparable to the current standard. Wear study demonstrated that volume of wear particles was an order of magnitude less with CFR-PEEK than UHMWPE.	The design will provide the benefits previously seen with the current standard, with improve long-term component wear and stability.	(+)
Scholes, SC (2008)	United Kingdom	CFR-PEEK acetabular cup, compared to UHMWPE	Wear testing Friction testing	Wear rates for the CFR-PEEK joints were considerably lower than UHMWPE joints.	The results show that this novel joint couple may potentially be an alternative solution for the reduction of osteolysis.	(+)
Scholes, SC (2009)	United Kingdom	(Pin material + Plate material) 1. CFR-PEEK + LC CoCrMo 2. CFR-PEEK PAN+ LC CoCrMo 3. CFR-PEEK PAN+ HC CoCrMo 4. CFR-PEEK pitch + HC CoCrMo	Pin-on-plate wear tests	Volumetric wear: PEEK LC CoCrMo-high wear rates with no running-in wear phase CFR-PEEK pins against the LC CoCrMo plates- showed no running-in wear period CFR-PEEK-PAN against HC CoCrMo- the running-in wear period was in the first 1.4 million cycles CFR-PEEK Pitch against HC CoCrMo had two wear phases: higher initial wear phase (1 million cycles) followed by a lower steady-state wear phase.	CFR-PEEK against CoCrMo (HC/LC) provided low wear rates. Study concluded with confidence that this material combination will perform well in orthopedic applications.	(+)
Scholes, SC (2009)	United Kingdom	Oxford® Partial Knee [CoCrMo tibial component and femoral component between a mobile pitch-based CFR-PEEK OPTIMA® meniscal bearing]	Wear test: Durham six-station knee wear simulator Friction Test: Durham friction stimulator II Lubrication Test	Wear tests: Loaded soak control gave very similar wear results to the unloaded soak control for this material combination. The medial joints gave higher wear than the lateral joints using both the loaded and the unloaded soak controls. Friction tests: The medial components gave slightly lower friction than the lateral components performed using carboxymethyl cellulose (CMC) or bovine serum (BS) as lubricant. A slight decrease in friction factors was found when BS was used as the lubricant for the medial and lateral bearings compared to CMC	CFR PEEK unicondylar knee joints performed well in these wear tests (lower volumetric wear than conventional metal-on-ultra-high-molecular-weight polyethylene prostheses) The friction tests showed that the joints were working within boundary-mixed lubrication. The low wear produced by these joints was due to the material combination and not the lubrication regime.	(+)
Brockett, CL (2012)	United Kingdom	36 mm diameter Biolox Delta ceramic and cobalt chrome heads paired with CFR-PEEK Pitch cups. Control: 36 mm diameter cross-linked UHMWPE cups	Friction wear test using a single station pendulum friction stimulator. Wear test method using a 10-station Prosim hip wear simulator.	The friction for both the CFR-PEEK bearings was significantly higher than the friction for the cross-linked UHMWPE. The mean volumetric wear rate was 0.3 mm3/Mc indicating that the ceramic-on-CFR-PEEK bearing to be a very low wearing option	CoCFR-PEEK bearings are a promising alternative bearing option for total hip replacement.	(+)
Dickinson, AS (2012)	United Kingdom	Composite hemi-pelvis implanted with acetabular cups made of either: -CoCr -UHMWPE -MOTIS CFR-PEEK	Surface strain measurement using Digital Image Correlation	CoCr and CFR-PEEK cups generated increased tensile and compressive cortex strains superior to the acetabular rim, whereas UHMWPE cup generated a global reduction in cortex strain. The CFR-PEEK cup produced the closest bone strain pattern to the intact case, increasing the average principal strain magnitude in the gage region by 12%.	The MOTIS CFR-PEEK composite acetabular cup produced the closest bone strain to the intact pelvis in the main load path compared to CoCr metal and UHMWPE. CFR-PEEK cups may produce a lower extent of internal cancellous bone stress shielding and induce less adverse bone adaptation, offering greater longevity.	(+)
Nakahara, I (2013)	Japan	CFR-PEEK composite (Cup + Stem) 1. Cement + Cement 2. Cement + Cementless 3. Cementless + Cement 4. Cementless + Cementless	Ovine model-unilateral hip replacement was performed using either a cementless or cemented prosthesis.	All animals recovered from surgery uneventfully. 11/15 animals were used to examine fixation of the cups and stems. Both cementless and cemented CFR-PEEK stems work well for fixation. Cup fixation may be difficult for both cemented and cementless types.	Reported stable in vivo fixation of CFR/PEEK prostheses in both cemented and cementless cases even under load-bearing condition. Results encourage the development of CFR/PEEK hip prostheses.	(+)
Steinberg, EL (2012)	Israel	Piccolo composite CFR-PEEK items: 1. 10 mm tibial nail 2. Dynamic compression plate 3. Proximal humeral plate 4. Distal volar radial plate	Four-point bending, static torsion of the nail and bending fatigue; debris generated at the connection between the CF-PEEK plate and titanium alloy screws	4-point bending stress of the tibial nail and dynamic and distal radius plates met acceptance criteria (similar to other commercially used nails). Torsion stiffness test results for CF were similar to commercial nails. All CF-PEEK devices underwent one million fatigue cycles without failure Debris filters indicated that the CF-PEEK had a lower debris weight than the titanium control.	CFR-PEEK OPTIMA passed the tests meeting the acceptable criteria and behaving similar to other commercial nails and plates	(+)
Maharaj, G (1994)	North America	CFR-PEEK in the femoral component of a total hip arthroplasty	Wear debris characterization Mechanical testing	Amount of debris generated is relatively small compared to UHMWPE. Zirconia heads remained well-attached to CFR-PEEK trunnions after 10 million cycles.	Indicates a stable, well-fixed interface.	(+/−)
Bruner, HJ (2010)	North America -	Titanium 6 x 45-mm pedicle screws (EXPEDIUM, DePuy Spine) couple with 5.5-mm rods made of either titanium, PEEK, or CFR-PEEK.	Biomechanical loading: -Pure moment loading Combined loading	No statistically significant differences between constructs.	CFR-PEEK rods have similar stiffness to PEEK and titanium alloy constructs in single-cycle, in vitro, biomechanical loading in the human lumbar spine.	(+/−)
Grupp, TM (2010)	Germany	Univariation F fixed bearing unicom-partmental knee design compared to experimental gliding surfaces made of CFR-PEEK pitch and CFR-PEEK PAN.	In vitro wear stimulation: Univariation F medial unicompartmental knee replacement with UHMWPE/CoCr29Mo6 compared to the experimental gliding surfaces made of CFR-PEEK Pitch and CFR-PEEK-PAN.	CFR-PEEK Pitch instead of polyethylene led to a significant reduction of cumulative wear but not substantially different from the wear rate of the clinical reference. The CFR-PEEK-PAN group showed no significant difference in the cumulative wear and wear rate. There was a wide scattering in wear behavior. There were huge variances in individual wear rates.	CFR-PEEK-PAN is unsuitable as a bearing material for fixed bearing knee articulations with low congruency. CFR-PEEK Pitch cannot be recommended as it remains doubtful whether it reduces wear compared to polyethylene.	(+/−)
Wang, A (1999)	North America	CFR-PEEK as bearing surfaces for total joint replacements (hip and knee)	Wear tests	Knee: CFR-PEEK composites exhibited significant higher wear rates than UHMWPE. Hip: CFR-PEEK composites showed a reduction in the wear rate compared to UHMWPE.	CFR-PEEK composites offer a far superior wear resistance over UHMWPE in the hip joint, but it not recommended for total knee replacements.	Hip (+) Knee (−)
(B) FIRST AUTHOR (YEAR)	LOCATION	MATERIALS ASSESSED	TESTS USED	RESULTS OF THE TEST (TECHNICAL DATA)	SAFETY (CONCLUSION)	OUTCOME
Brantigan, JW (1993)	North America	CFR-PEEK implant cage	Clinical and radiographic assessment	Successful radiographic fusion in all cases. Clinically, 20/26 patients categorized as either “excellent” or “good”.	The clinical and fusion results represent the justification for a larger formal study of the safety and efficacy of the device.	(+)
Rousseau, MA (2007)	France	CFR-PEEK interbody cage at the lumbar spine	Physical examination using the classification of Brantigan and Steffee Radiologic evaluation	Clinical outcomes were excellent or good in 49 of 57 patients. Fusion was definite in 56 of 57 cases. No revision surgery. At follow up, local lordosis decreased in 13 cases.	Lumbar circumferential arthrodesis using CFR-PEEK cages provided good clinical results and fusion rate, but lordosis correction was not maintained at follow-up.	(+)
Nakahara, I (2012)	Japan	CFR-PEEK hip stem	Radiographic and histologic assessment	CFR-PEEK stems remained intact without any evidence of delamination, microfracture, or particulate migration in appearance No evidence of any wear debris or any inflammatory reaction in the surrounding soft tissue. Bone on growth fixation achieved in 2 of 4 cases of CFR-PEEK stems and in all 5 cases of titanium stems. CFR-PEEK cases showed minimal stress shielding while 3 of 5 titanium cases demonstrated typical osteopenia associated with stiff metal stems. Bone resorption and osteopenia observed with titanium stems was not found with CFR-PEEK design.	The lower stiffness of the CFR-PEEK has a positive effect on suppression of the bone resorption due to stress shielding.	(+)
Pace, N (2008)	Italy	CFR-PEEK acetabular cup	Clinical assessment Harris Hip Score (HHS) Radiographic examination	Mean preoperative HHS improved from 52 to 90 points. 1 of 28 patients had a revision due to a septic loosening. Radiographs revealed that everyone was stable.	The presented findings show the short-term efficacy of the implant, but longer follow-ups and a larger number of patients are needed. These results should be considered encouraging.	(+)
Heary, RF (2011)	North America	CFR-PEEK cage (DePuy Spine)	Clinical examination (Odom criteria) and plain radiographs.	39 (97.5%) of patients had solid fusions at a mean follow-up of 43 months. No deterioration of neurological function compared with preoperative status.	CFR-PEEK cages are effective for achieving thoracolumbar fusion. Excellent clinical and radiographic results were achieved.	(+)