We have found that the use of a novel ceramic implant as a replacement for a focal cartilage defect leads to secure implant fixation, while not causing significant degradation in opposing articular cartilage.
Within hours of surgical implantation animals were fully ambulating with no changes in the function of their hindlimbs. For the duration of the experiment no lameness to their hindlimbs was observed, indicating that immediate mobilization of the treated limb is possible with the minimally invasive press-fit implantation of the device.
In addition, the possibility for early weight bearing is supported by the postoperative radiographs that indicated that no loosening of the implants had taken place, thereby enabling faster healing and return to play.
Although the surgical procedure required the manual application of a series of custom guides to produce the desired excavated footprint for the implant, the tolerances and techniques were precise enough to enable a firm press fit of the porous cones extending from the implant. The press-fit implantation of the device was shown to be secure enough for normal activity immediately following surgery until adequate bone apposition and ingrowth had occurred. SEM and biomechanical test results indicate that this happened within 12 weeks, at which time the novel porous cone design had led to complete implant fixation. Despite significant ingrowth, the lower pull-out strength for the 24-week group relative to the 12-week group occurred from failure at the base of the cones during testing in two specimens. Further investigation of this failure mode seems to indicate that the ingrown cones exhibit strength greater than the tensile strength of the porous ceramic. It should be noted that this testing technique was used to help define bone ingrowth and not to characterize the mechanical strength of the material. The specific characterization of this material for implant use was conducted prior to this animal study by the sponsor and determined to be adequate for the device application. Biomechanically, tensile loads would be expected to be relatively low in vivo, given that compressive loads and possibly shear loads dominate during normal gait activities. An argument could be made that distinguishable asymmetry related to the ingrowth of the independent cones, i.e., one displaying significantly less ingrowth or becoming loose relative to the other, could cause a tensile condition, but this condition did not appear with any implant evaluated in this study. Most pull-out failures occurred at the tip of the cones, effectively measuring the specific bone/cone interface. Despite the potential for tensile failure, the cones were found to be structurally sound enough to maintain implant placement and the integrity of a continuous articular surface throughout the study. In light of this finding, however, future device design improvements using this material are being developed.
The XRD measurements for percent monoclinic showed very low levels of phase transformation over the test period. These results suggest stability of the ceramic material against aging due to low-temperature degradation for this application.
Although cartilage coverage of the articular surface of the implant increased significantly over time, the characteristics were mostly fibro-cartilaginous in nature, which is similar to what has been seen with other cartilage replacement devices [34
]. Although not of similar material properties as native articular cartilage, the coverage seems to help create a smooth transition from the healthy cartilage to the polished articular surface of the implant. The coverage of the implant with fibro-cartilage is similar to what has been observed with cartilage plugs where a ‘flow’ of cartilage surrounding the defect occurs [45
]. Despite the nonindigenous nature of the ‘flowing’ cartilage at the articular surface, it can be argued that the increased cartilage coverage does not have a detrimental effect on the opposing cartilage on the tibial plateau based on the Safranin O intensity results presented (). However, correlations were observed between percent implant articular surface length covered by cartilage and gross Collins score of the medial tibial plateau (Pearson's correlation: 0.241, P
=.427), Mankin score of the medial tibial plateau (Pearson's correlation: 0.355, P
= .235), and Safranin O intensity of Region 1 (outer layer) of the medial tibial plateau (Pearson's correlation: 0.104, P
=.734). These correlations, however, were weak and statistically non-significant. Hence, fibro-cartilage overgrowth might play a role with some degeneration but in the time frame presented here this degeneration does not become significant. Finally the preservation of healthy hyaline cartilage surrounding the implant supports the usage of a ceramic over a cartilage plug, where localized ‘flow’ of fibro-cartilage over the plug has been shown to lead to plug degeneration and frayed surrounding cartilage for both deep and superficial defects [46
The lower Collins and Mankin scores in the UC group relative to the other groups seem to be due to surgical exposure of the cartilage, as reflected in the similar results between the control and 12/24-week groups. This observation is supported by studies that have shown histochemical and ultrastructural changes in articular cartilage immediately following surgery [48
]. In addition, since no changes were seen for the Mankin scoring and the Safranin O intensity measurements between the lateral and medial plateaus, one can assume that the degenerative changes caused by the implant itself are nonsignificant up to 24 weeks. However, sacrificing animals at later time points could potentially reveal significant changes not observed within the examined time frame.
This study does have limitations. Despite using contra lateral limbs and within-limb controls (), group size could potentially be too small for nonsignificance to be accurately measured for the Safranin O outcome measures. However, the significantly larger group sizes used for the cross-cartilage measures revealed results that paralleled the Safranin O results, thus supporting the overall conclusion. In addition, the potentially small-sized groups do not negate the validity of the significant findings for several key measures. This includes the significant increase in pull-out strength paralleled by the significant increase in bone ingrowth over time measured with SEM. Another limitation is the duration that animals were kept with the implant. Twenty-four weeks is a medium-sized timeframe that gives a good estimation of the initial cartilage and bone response to the implantation of the ceramic as an articular surface. However longer term projections are desired and will be used in a subsequent study.
In summary, the use of a ceramic implant appears to be an effective, secure focal cartilage replacement up to 24 weeks that may increase the therapeutic options for focal cartilage lesions. Further studies are needed to determine any long-term effects beyond 24 weeks.