The Expression Levels of Toll-like Receptors after Metallic Particle and Ion Exposition in the Synovium of a Murine Model.

To date, the exact role of specific Toll-like receptors (TLRs) in regulating immune reactivity to metallic byproducts of orthopedic implants has not been fully clarified. In light of the situation, our objective in this investigation was to assess the expression levels of surface TLRs after metallic particle and ion exposure in an established animal model. Ten female BALB/c mice in each group received intra-articular injections of phosphate buffer (PBS) (control), metallic particles (MP), and metallic ions (MI), respectively. Seven days later, immunohistochemical staining was undertaken in the synovial layer of the murine knee joints using anti-TLR 1, 2, 4, 5, and 6 polyclonal antibodies. In addition to increased cellular infiltrates and a hyperplastic synovial membrane, the MP group showed significantly elevated TLR expression compared to the control group and had higher TLR 1-, 4-, and 6-positive cells than the MI group (p < 0.0167). TLR 4- and TLR 6-positive cells were significantly augmented for the MI group compared to the control group (p < 0.0167). Additionally, greenish corrosion particles found in the necrotic tissue suggested that metallic particles might release a certain level of locally toxic metallic ions in vivo.

Biological Reactions to Metal Particles and Ions in the Synovial Layer of Mice.

Metal particles and ions released from implants not only have a fundamental effect on the longevity of total joint replacements, but can also be disseminated to remote organs. Periprosthetic tissues harvested during revision surgeries mainly reflect end-stage failure but may not adequately reveal initial biological reactions and systemic side effects. Therefore, primary reactions caused by metal particles and ions were investigated in an established murine model. Left knee joints in three groups, each consisting of ten female BALB/c mice, received injections of metal ions (MI), metal particles (MP) and phosphate-buffered saline (PBS) (control). Seven days after the injection, immunohistochemical analyses of the synovial layer were performed with respect to some biological markers including Tumor necrosis factor -α (TNF-α), Interleukin-6 (IL-6), Interleukin-1ß (IL-1ß), Cluster of Differentiation 45 (CD45), Cluster of Differentiation 68 (CD68) and Cluster of Differentiation 3(CD3). The MP group showed significantly enhanced proinflammatory cytokine expression (TNF-α, IL-6 and IL-1ß) compared with the other groups (p < 0.05). Interestingly, CD3, as a marker for T lymphocytes, did not increase in any of the groups. The MI group showed a significantly increased expression of CD45 compared with the control group (p < 0.05). Therefore, during the primary process, metal particles have stronger pro-inflammatory potential than metal ions, and T lymphocytes did not seem to be activated in our murine model. Systemic reactions caused by metal particles and ions were found by observing the untreated right knees.

Local Biological Reactions and Pseudotumor-Like Tissue Formation in relation to Metal Wear in a Murine In Vivo Model.

Metal wear debris and released ions (CoCrMo), which are widely generated in metal-on-metal bearings of hip implants, are also found in patients with metal-on-polyethylene bearings due to the mechanically assisted crevice corrosion of modular taper junctions, including head-neck and neck-stem taper interfaces. The resulting adverse reactions to metal debris and metal ions frequently lead to early arthroplasty revision surgery. National guidelines have since been published where the blood metal ion concentration of patients must consistently be monitored after joint replacement to prevent serious complications from developing after surgery. However, to date, the effect of metal particles and metal ions on local biological reactions is complex and still not understood in detail; the present study sought to elucidate the complex mechanism of metal wear-associated inflammation reactions. The knee joints in 4 groups each consisting of 10 female BALB/c mice received injections with cobalt chrome ions, cobalt chrome particles, and ultra-high-molecular-weight polyethylene (UHMWPE) particles or PBS (control). Seven days after injection, the synovial microcirculation and knee joint diameter were assessed via intravital fluorescence microscopy followed by histological evaluation of the synovial layer. Enlarged knee diameter, enhanced leukocyte to endothelial cell interactions, and an increase in functional capillary density within cobalt chrome particle-treated animals were significantly greater than those in the other treatment groups. Subsequently, pseudotumor-like tissue formations were observed only in the synovial tissue layer of the cobalt chrome particle-treated animals. Therefore, these findings strongly suggest that the cobalt chrome particles and not metal ions are the cause for in vivo postsurgery implantation inflammation.

Normal radiological unossified hip joint space and femoral head size development during growth in 675 children and adolescents.

Evaluation of hip joint space width during child growth is important to aid in the early diagnosis of hip pathology in children. We established reference values for hip joint space and femoral head size for each age. Hip joint space development during growth was retrospectively investigated medial and cranial in 1350 hip joints of children using standard anteroposterior supine plain pelvic radiographs. Maximum capital femoral epiphysis diameter and femoral radii were further more investigated. Hip joint space values show a slow decline during growth. Joint space was statistically significantly (p < 0.006) larger in boys than girls. Our hip joint space measurements on supine subjects seem slightly larger than those reported by Hughes on standing subjects. Evaluation of the femoral head diameter and the radii showed a size curve quite parallel to the known body growth charts. Radii medial and perpendicular to the physis are not statistically significantly different. We recommend to compare measurements of hip joint space at two locations to age dependent charts using the same imaging technique. During growth, a divergence in femoral head size from the expected values or loss of the spherical shape should raise the question of hip disorder. Clin. Anat. 30:267-275, 2017. © 2016 Wiley Periodicals, Inc.

Impact of vitamin E-blended UHMWPE wear particles on the osseous microenvironment in polyethylene particle-induced osteolysis.

Aseptic loosening mediated by wear particle-induced osteolysis (PIO) remains the major cause of implant loosening in endoprosthetic surgery. The development of new vitamin E (α-tocopherol)-blended ultra-high molecular weight polyethylene (VE-UHMWPE) with increased oxidation resistance and improved mechanical properties has raised hopes. Furthermore, regenerative approaches may be opened, as vitamin E supplementation has shown neuroprotective characteristics mediated via calcitonin gene-related peptide (CGRP), which is known to affect bone remodeling in PIO. Therefore, the present study aimed to further clarify the impact of VE-UHMWPE wear particles on the osseous microenvironment and to identify the potential modulatory pathways involved. Using an established murine calvaria model, mice were subjected to sham operation (SHAM group), or treated with UHMWPE or VE-UHMWPE particles for different experimental durations (7, 14 and 28 days; n=6/group). Morphometric analysis by micro-computed tomography detected significant (p<0.01) and comparable signs of PIO in all particle-treated groups, whereas markers of inflammation [tumor necrosis factor (TNF)-α/tartrate resistant acid phosphatase (TRAP) staining] and bone remodeling [Dickkopf-related protein 1 (DKK-1)/osteoprotegerin (OPG)] were most affected in the early stages following surgery. Taking the present data into account, VE-UHMWPE appears to have a promising biocompatibility and increased ageing resistance. According to the α-CGRP serum levels and immunohistochemistry, the impact of vitamin E on neuropeptidergic signaling and its chance for regenerative approaches requires further investigation.

Discrepancy between sonographic and radiographic values after ultrasound-monitored treatment of developmental dysplasia of the hip.

INTRODUCTION: The purpose of the study was to examine the accordance between the actually used sonographic and radiographic standard values after ultrasound-monitored treatment of developmental dysplasia of the hip (DDH). MATERIAL AND METHODS: One hundred and fifty-three (119 children) ultrasound-monitored treated hips (initial staging according to Graf: type IIc-IV) which attained normal ultrasound findings (type I according to Graf) during treatment and underwent an anteroposterior radiograph of the pelvis at the time of starting walking (mean age 18.6 months) were evaluated retrospectively. RESULTS: While all hips showed normal sonographic values (Graf type I), 26 (17%) showed mild and 17 (11.1%) severe dysplasia (by measuring the acetabular index) according to the radiographic Toennis classification system, and 29 (19%) showed mild and 48 (31.4%) severe dysplasia according to the Wiberg centre-edge angle. CONCLUSIONS: This data show that the actually used sonographic and radiographic standard values concerning DDH do not correlate appropriately. It must be put up for discussion whether the radiographic standard values might be too strict. Further criteria must be developed to better assess the prognosis of residual dysplasia.

Analysis of Carbon Fiber Reinforced PEEK Hinge Mechanism Articulation Components in a Rotating Hinge Knee Design: A Comparison of In Vitro and Retrieval Findings.

Carbon fiber reinforced poly-ether-ether-ketone (CFR-PEEK) represents a promising alternative material for bushings in total knee replacements, after early clinical failures of polyethylene in this application. The objective of the present study was to evaluate the damage modes and the extent of damage observed on CFR-PEEK hinge mechanism articulation components after in vivo service in a rotating hinge knee (RHK) system and to compare the results with corresponding components subjected to in vitro wear tests. Key question was if there were any similarities or differences between in vivo and in vitro damage characteristics. Twelve retrieved RHK systems after an average of 34.9 months in vivo underwent wear damage analysis with focus on the four integrated CFR-PEEK components and distinction between different damage modes and classification with a scoring system. The analysis included visual examination, scanning electron microscopy, and energy dispersive X-ray spectroscopy, as well as surface roughness and profile measurements. The main wear damage modes were comparable between retrieved and in vitro specimens (n = 3), whereby the size of affected area on the retrieved components showed a higher variation. Overall, the retrieved specimens seemed to be slightly heavier damaged which was probably attributable to the more complex loading and kinematic conditions in vivo.

Discrepancy between morphological findings in juvenile osteochondritis dissecans (OCD): a comparison of magnetic resonance imaging (MRI) and arthroscopy.

PURPOSE: The aim of this study was to assess the reliability of preoperative MRI for the staging of osteochondritis dissecans (OCD) lesions of the knee and the talus in juvenile patients, using arthroscopy as the gold standard of diagnosis. METHODS: Sixty-three juvenile patients (range 8-16 years) with an OCD of the knee or the talus underwent arthroscopy after MRI. In 54/9 out of 63 cases, 1.5/3 T MR scanners were used. The OCD stage was classified according the staging criteria of Dipaola et al. Arthroscopic findings were compared with MRI reports in each patient. RESULTS: From the 63 juvenile patients, MRI/arthroscopy revealed a stage I OCD in 4/19 patients, stage II in 31/22 patients, stage III in 22/9 patients and stage IV in 6/6 patients. No osteochondral pathology was evident in arthroscopy in seven out of 63 patients. The overall accuracy of preoperative MRI in staging an OCD lesion of the knee or the talus was 41.3%. In 33 out of 63 patients (52.4%), arthroscopy revealed a lower OCD stage than in the preoperative MRI grading, and in four out of 63 cases (6.4%), the intraoperative arthroscopic grading was worse than in preoperative MRI prior to surgery. The utilization of the 3 T MRI provided a correct diagnosis with 44.4%. CONCLUSIONS: Even with today's modern MRI scanners, it is not possible to predict an accurate OCD stage in children. The children's orthopaedist should not solely rely on the MRI when it comes to the decision to further conservative or surgical treatment of a juvenile OCD, but rather should take surgical therapy in consideration within persisting symptoms despite a low OCD stage provided by MRI. LEVEL OF EVIDENCE: III.

PMMA third-body wear after unicondylar knee arthroplasty decuples the UHMWPE wear particle generation in vitro.

INTRODUCTION: Overlooked polymethylmethacrylate after unicondylar knee arthroplasty can be a potential problem, since this might influence the generated wear particle size and morphology. The aim of this study was the analysis of polyethylene wear in a knee wear simulator for changes in size, morphology, and particle number after the addition of third-bodies. MATERIAL AND METHODS: Fixed bearing unicondylar knee prostheses (UKA) were tested in a knee simulator for 5.0 million cycles. Following bone particles were added for 1.5 million cycles, followed by 1.5 million cycles with PMMA particles. A particle analysis by scanning electron microscopy of the lubricant after the cycles was performed. Size and morphology of the generated wear were characterized. Further, the number of particles per 1 million cycles was calculated for each group. RESULTS: The particles of all groups were similar in size and shape. The number of particles in the PMMA group showed 10-fold higher values than in the bone and control group (PMMA: 10.251 × 10(12); bone: 1.145 × 10(12); control: 1.804 × 10(12)). CONCLUSION: The addition of bone or PMMA particles in terms of a third-body wear results in no change of particle size and morphology. PMMA third-bodies generated tenfold elevated particle numbers. This could favor an early aseptic loosening.

Increase in the tibial slope reduces wear after medial unicompartmental fixed-bearing arthroplasty of the knee.

Introduction. Unicompartmental arthroplasty of the knee in patients with isolated medial osteoarthritis gives good results, but survival is inferior to that of total knee prosthesis. Knees may fail because positioning of the prosthesis has been suboptimal. The aim of this study was to investigate the influence of the tibial slope on the rate of wear of a medial fixed-bearing unicompartmental knee arthroplasty. Materials and Methods. We simulated wear on a medial fixed-bearing unicompartmental knee prosthesis (Univation) in vitro with a customised, four-station, and servohydraulic knee wear simulator, which exactly reproduced the walking cycle (International Organisation for Standardisation (ISO) 14243-1:2002(E)). The medial prostheses were inserted with 3 different posterior tibial slopes: 0°, 4°, and 8° (n = 3 in each group). Results. The wear rate decreased significantly between 0° and 4° slope from 10.4 (SD 0.62) mg/million cycles to 3.22 (SD 1.71) mg/million cycles. Increasing the tibial slope to 8° did not significantly change the wear rate. Discussion. As an increase in the tibial slope reduced the wear rate in a fixed-bearing prosthesis, a higher tibial slope should be recommended. However, other factors that are influenced by the tibial slope (e.g., the tension of the ligament) must also be considered.

Experimental testing of total knee replacements with UHMW-PE inserts: impact of severe wear test conditions.

Aseptic implant loosening due to inflammatory reactions to wear debris is the main reason for the revision of total knee replacements (TKR). Hence, the decrease in polyethylene wear particle generation from the articulating surfaces is aimed at improving implant design and material. For preclinical testing of new TKR systems standardized wear tests are required. However, these wear tests do not reproduce the entire in vivo situation, since the pattern and amount of wear and subsequent implant failure are underestimated. Therefore, daily activity, kinematics, implant aging and position, third-body-wear and surface properties have to be considered to estimate the wear of implant components in vivo. Hence, severe test conditions are in demand for a better reproduction of the in vivo situation of TKR. In the present article an overview of different experimental wear test scenarios considering clinically relevant polyethylene wear situations using severe test conditions is presented.

Biotribology of a mobile bearing posterior stabilised knee design--effect of motion restraint on wear, tibio-femoral kinematics and particles.

The objective of our study was to evaluate the impact of a biphaseal anterior-posterior (AP) and internal-external (IE) motion restraint system on the wear behaviour, tibio-femoral kinematics and particle release of a mobile bearing posterior stabilised knee design in comparison to the widely used linear restraint. in vitro wear simulation was performed using a posterior stabilised total knee replacement with a mobile rotating platform gliding surface design to compare the standard ISO 14243-1:2002 (E) protocol with a linear AP and IE motion restraint and the new ISO 14243-1:2009 (E) protocol with a biphaseal AP and IE motion restraint. For the mobile gliding surfaces, an increase in wear rate by more than a magnitude was measured applying the biphaseal protocol (8.5±1.6 mg/million cycles) in a direct comparison to the linear protocol (0.33±0.07 mg/million cycles), with statistically significant difference. The amplitudes of AP displacement were 3.22±0.47 mm for the biphaseal test, compared to 1.97±0.22 mm in the linear test and the amplitudes of the IE rotation angle had mean values of 7.32°±0.91° under the biphaseal setup, compared to 1.97°±0.14° under linear motion restraint test conditions. From our observations, we conclude that the changes in AP translation and IE rotation motion restraints from ISO linear to ISO biphaseal test conditions highly impact the knee joint kinematics and wear behaviour of a mobile bearing posterior stabilised knee design.

Biotribology of a vitamin E-stabilized polyethylene for hip arthroplasty - Influence of artificial ageing and third-body particles on wear.

The objective of our study was to evaluate the influence of prolonged artificial ageing on oxidation resistance and the subsequent wear behaviour of vitamin E-stabilized, in comparison to standard and highly cross-linked remelted polyethylene (XLPE), and the degradation effect of third-body particles on highly cross-linked remelted polyethylene inlays in total hip arthroplasty. Hip wear simulation was performed with three different polyethylene inlay materials (standard: γ-irradiation 30 kGy, N2; highly cross-linked and remelted: γ-irradiation 75 kGy, EO; highly cross-linked and vitamin E (0.1%) blended: electron beam 80 kGy, EO) machined from GUR 1020 in articulation with ceramic and cobalt-chromium heads. All polyethylene inserts beneath the virgin references were subjected to prolonged artificial ageing (70°C, pure oxygen at 5 bar) with a duration of 2, 4, 5 or 6 weeks. In conclusion, after 2 weeks of artificial ageing, standard polyethylene shows substantially increased wear due to oxidative degradation, whereas highly cross-linked remelted polyethylene has a higher oxidation resistance. However, after enhanced artificial ageing for 5 weeks, remelted XLPE also starts oxidate, in correlation with increased wear. Vitamin E-stabilized polyethylene is effective in preventing oxidation after irradiation cross-linking even under prolonged artificial ageing for up to 6 weeks, resulting in a constant wear behaviour.

Elevated cytokine expression of different PEEK wear particles compared to UHMWPE in vivo.

Due to their mechanical properties, there has been growing interest in poly-ether-ether-ketone (PEEK) and its composites as bearing material in total and unicompartmental knee arthroplasty. The aim of this study was to analyze the biological activity of wear particles of two different (pitch and PAN) carbon-fiber-reinforced- (CFR-) PEEK varieties in comparison to ultra-high-molecular-weight-polyethylene (UHMWPE) in vivo. The authors hypothesized no difference between the used biomaterials. Wear particle suspensions of the particulate biomaterials were injected into knee joints of Balb/c mice, which were sacrificed after seven days. The cytokine expression (IL-1ß, IL-6, TNF-α) was analyzed immunohistochemically in the synovial layer, the adjacent bone marrow and the articular cartilage. Especially in the bone marrow of the two CFR-PEEK varieties there were increased cytokine expressions compared to the control and UHMWPE group. Furthermore, in the articular cartilage the CFR-PEEK pitch group showed an enhanced cytokine expression, which could be a negative predictor for the use in unicondylar knee systems. As these data suggest an increased proinflammatory potential of CFR-PEEK and its composites in vivo, the initial hypothesis had to be refuted. Summarizing these results, CFR-PEEK seems not to be an attractive alternative to UHMWPE as a bearing material, especially in unicompartmental knee arthroplasty.

Increase of tibial slope reduces backside wear in medial mobile bearing unicompartmental knee arthroplasty.

BACKGROUND: Unicondylar knee arthroplasty is a good alternative for patients in monocompartmental osteoarthritis. The revision rate in unicondylar knee arthroplasty is higher than in total knee arthroplasty. The influence of the tibial slope on wear in unicondylar knee arthroplasty has not been investigated so far. METHODS: The influence of the tibial slope on wear was investigated in mobile bearing unicondylar knee prosthesis. This was positioned with four different tibial slopes (-4°, 0°, 4°, 8°) in a knee wear simulator simulating the human gait in a plane according to ISO 14243-2:2002(E). After this a kinematic analysis was performed and the inlays were observed under reflected-light-microscopy. FINDINGS: Wear was significantly reduced with an increasing tibial slope (0°: 3.46 mg/millioncycles, SD: 0.59, 4° slope: 1.52 mg/millioncycles, SD: 0.06, 8° slope group: 0.99 mg/millioncycles, SD: 0.42). An anterior slope of -4° also reduced wear (2.08 mg/millioncycles, SD: 0.37). Kinematic analysis revealed a reduced translation between the inlay and the tibia with an increasing tibial slope. The backside of the inlays of the 4° and 8° slope group showed less wear pattern when observed under reflected-light microscopy. INTERPRETATION: Increasing the tibial slope led to a reduced translation between the inlay and the prosthesis in the analysed mobile-bearing unicondylar knee arthroplasty and with this to a reduced backside wear. A tibial slope between 4 and 8° can be recommended in mobile UKA to reduce wear, however, the influence on the ligaments has to be considered and needs to be investigated in further studies.

Characterization of polyethylene wear particle: The impact of methodology.

Due to the prevalence of problems caused by wear particles, the reduced durability of total joint replacements is well documented. The characterization of wear debris enables the size and morphology of these wear particles to be measured and provides an assessment of the biological response in vivo. However, the impact of different methodologies of particle analysis is not yet clear. Hence, the aim of this investigation was to analyze the influence of different particle characterization methods performed by three research centers within the scope of a "round robin test". To obtain knowledge about possible pitfalls, single steps of the particle characterization process (storage, pore size of the filter, coating durations by gold sputtering and scanning electron microscopy (SEM) magnification) were analyzed. The round robin test showed significant differences between the research groups, especially for the morphology of the particles. The SEM magnification was identified as having the greatest influence on the size and shape of the particles, followed by the storage conditions of the wear particle containing lubricant. Gold sputter coating and filter pore size also exhibit significant effects. However, even though they are statistically significant, it should be emphasized that the differences are small. In conclusion, particle characterization is a complex analytical method with a multiplicity of influencing factors. It becomes apparent that a comparison of wear particle results between different research groups is challenging.

Knee wear simulation under conditions of highly demanding daily activities--influence on an unicompartmental fixed bearing knee design.

The objectives of our in vitro study were to evaluate a knee wear simulation based on patient daily activities in combination with artificial ageing of polyethylene inserts to create an optimised simulation of in vivo wear modes. A wear simulation was performed on fixed bearing unicompartmental knee arthroplasty (UKA) devices in a direct comparison of level walking (as given by the ISO 14243-1:2002(E) profiles) and in a customised test configuration based on activities for level walking (10%), stairs ascending (40%), stairs descending (40%), chair rising (8%) and deep squatting (2%). The cumulative gravimetric wear was estimated to be 15.3mg for level walking (ISO) and 69.6 mg for high demanding activities (HDA). The gravimetric wear rate of the ISO group was 3.0mg/million cycles, compared to 11.7 mg/million cycles for the HDA protocol. Level walking wear testing conditions (ISO) and artificial ageing alone is not sufficient to reproduce in vivo failure modes. After 3 million cycles all gliding surfaces of the HDA group developed in the tibio-femoral articulation markable areas of structural material fatigue and delamination. In conclusion a combination of artificial ageing to clinical relevant oxidation grades and a sequence of various high demanding daily patient activities is necessary to represent a revised in vitro behaviour of abrasive-adhesive wear and delamination in artificial knee replacements.

The influence of third-body particles on wear rate in unicondylar knee arthroplasty: a wear simulator study with bone and cement debris.

The reduced intraoperative visibility of minimally invasive implanted unicondylar knee arthroplasty makes it difficult to remove bone and cement debris, which have been reported on the surface of damaged and retrieved bearings. Therefore, the aim of this study was to analyze the influence of bone and cement particles on the wear rate of unicompartmental knee prostheses in vitro. Fixed bearing unicompartmental knee prostheses were tested using a knee-wear-simulator according to the ISO standard 14243-1:2002(E) for 5.0 million cycles. Afterwards bone debris (particle size 671 ± 262 µm) were added to the test fluid in a concentration of 5 g/l for 1.5 million cycles, followed by 1.5 million cycles blended with cement debris (particle size 644 ± 186 µm) in the same concentration. Wear rate, knee-kinematics and wear-pattern were analyzed. The wear rate reached 12.5 ± 1.0 mm³/million cycles in the running-in and decreased during the steady state phase to 4.4 ± 0.91 mm³/million cycles. Bone particles resulted in a wear rate of 3.0 ± 1.27 mm³/million cycles with no influence on the wear rate compared to the steady state phase. Cement particles, however, lead to a significantly higher wear rate (25.0 ± 16.93 mm³/million cycles) compared to the steady state phase. The careful removal of extruded cement debris during implantation may help in reducing wear rate. Bone debris are suggested to have less critical influence on the prostheses wear rate.