Pseudotumors in Small-Head Metal-on-Metal Total Hip Arthroplasties at a Minimum Follow-Up of 20 Years.

BACKGROUND: Metal-on-metal (MOM) surfaces in total hip arthroplasty (THA) have been used widely. Serum cobalt and chromium levels have been the standard investigation for follow-up examinations, but magnetic resonance imaging (MRI) with metal artifact reducing sequences has shown good results in detecting pseudotumors. The aim of this study is to survey a significant correlation among MRI findings, serum metal levels, and clinical scores in patients with small-head MOM implants and if serum cobalt and chromium levels are sufficient in detecting patients with pseudotumors in the long-term follow-up. METHODS: At a minimum follow-up of 20 years, 26 patients (29 THAs) of the original 98 patients (105 THAs) included in this study between November 1992 and May 1994 were available for follow-up examination. Clinical scores, serum metal ion levels, and MRIs were obtained. RESULTS: We found mean serum cobalt levels of 1.87 µg/L (±3.44) and chromium levels of 2.23 µg/L (±2.96) and very good clinical and functional results (mean Harris Hip Score 88.6) in the long-term follow-up. Pseudotumors were detected in MRIs of 21 hips. There were no significant differences between patients with or without pseudotumors regarding serum metal levels and the correlation for clinical outcome scores, demographic data, and cup inclination. The cumulative rate of survival was still at 91.4% at 22.8 years. CONCLUSION: This study presents the first published data on small-head MOM hips, comparing metal ion levels, pseudotumors, clinical, and radiological results in a follow-up period of more than 20 years and reveals that serum metal levels are not significantly higher in patients with pseudotumors. LEVEL OF EVIDENCE: Therapeutic Level III.

Inferior performance of established and novel serum inflammatory markers in diagnosing periprosthetic joint infections.

PURPOSE: Besides other diagnostic test methods, established serum inflammatory markers such as serum C-reactive protein or leukocyte count are widely used preoperatively to aid in diagnosing periprosthetic joint infections (PJI). Although low accuracies were reported, these parameters are easily accessible and routinely available. Novel biomarkers with promising results in diagnosing PJI (platelet count to mean platelet volume ratio) or other infectious conditions (percentage of neutrophils, neutrophils to lymphocytes ratio) were described. The purpose of this study was to investigate the diagnostic value of established and novel serum inflammatory biomarkers for the diagnosis of PJI so as to compare the results to find the serum inflammatory marker with the best performance. METHODS: In 177 patients with a previous total hip (n = 91) or knee (n = 86) arthroplasty and indicated revision surgery, the diagnostic value of the routinely available serum inflammatory markers C-reactive protein (CRP), white blood cell count (WBC), percentage of neutrophils (%N), neutrophils to lymphocytes ratio (NLR), fibrinogen and platelet count to mean platelet volume ratio (PC/mPV) were examined retrospectively via receiver operating characteristic curve analysis (AUC). The curves were compared using the z-test. RESULTS: Sensitivities of serum CRP, WBC, %N, NLR, fibrinogen and PC/mPV were calculated with 68%, 36%, 66%, 63%, 69% and 43%, respectively. Specificities were 87%, 89%, 67%, 73%, 89% and 81%, respectively. Serum CRP (0.78) and fibrinogen (0.79) showed significantly better AUCs compared with serum WBC (0.63), %N (0.67), NLR (0.68) and PC/mPV (0.62) (p < 0.0001). Patients with PJI caused by a low-virulent microorganism (median CRP: 17.6 mg/L) obtained lower CRP levels compared with infections caused by high-virulent microorganisms (median CRP: 49.2 mg/L; p = 0.044). The combination of CRP and fibrinogen showed a better sensitivity (77%) with similar specificity (83%) than one method alone but not at a significant level (CRP (p = 0.200); fibrinogen (p = 0.437)). CONCLUSION: Serum CRP and fibrinogen showed the best accuracies among these widely available serum inflammatory parameters. However, due to the insufficient performance, these biomarkers can only be recommended as suggestive criteria in diagnosing PJI. The preoperative workup should always be complemented by more specific tests such as synovial fluid analysis.

Total hip arthroplasty using imageless computer-assisted hip navigation: a prospective randomized study.

In a prospective randomized study of two groups of 65 patients each, we compared the acetabular component position when using the imageless navigation system compared to the freehand conventional technique for cementless total hip arthroplasty. The position of the component was determined postoperatively on computed tomographic scans of the pelvis. There was no significant difference for postoperative mean inclination (P = 0.29), but a significant difference for mean postoperative acetabular component anteversion (P = 0.007), for mean deviation of the postoperative anteversion from the target position of 15° (P = 0.02) and for the outliers regarding inclination (P = 0.02) and anteversion (P < 0.05) between the computer-assisted and the freehand-placement group. Our results demonstrate the importance of imageless navigation for the accurate positioning of the acetabular component.

A cementless hip system with a new surface for osseous integration.

PURPOSE: The failure of total hip systems caused by wear-particle-induced loosening has focused interest on factors potentially affecting wear rate. Remnants of the blasting material were reported on grit-blasted surfaces for cementless fixation. These particles are believed to cause third-body wear and implant loosening. The purpose of this study was to evaluate the early clinical and radiological outcomes of a cementless hip system with a new, contamination-free, roughened surface with regard to prosthesis-related failures. METHODS: Between May 2004 and March 2009, 202 consecutive primary total hip arthroplasties (THAs) (192 patients with a mean age of 62.6 years) were performed using a cementless stem (Hipstar®) and a hemispherical acetabular cup (Trident®). RESULTS: At a minimum follow-up of two years, five revisions (2.5%) due to aseptic loosening of the stem and three (1.5%) of the cup were necessary. The cumulative rate of prostheses survival, counting revision of both components and with aseptic failure as end point, was 92.9% at 8.8 years. Radiolucent lines up to three millimetres were evaluated in the proximal part of the femur in 61% of cases. CONCLUSIONS: Although the incidence of radiolucent lines was decreased, the revision rate was considerably increased compared to other uncemented hip implants with grit-blasted surfaces in the short- to mid-term follow-up of our study. Subsequent studies are needed to confirm whether these changes in implant material and surface affect the radiological and clinical outcome in the long term.

Bacterial adherence to different components of total hip prosthesis in patients with prosthetic joint infection.

PURPOSE: The purpose of our study was to evaluate and quantify the bacterial adherence to the different components of total hip prosthesis. METHODS: The bacterial load of 80 retrieved hip components from 24 patients was evaluated by counting of colony-forming units (CFU) dislodged from component surfaces using the sonication culture method. RESULTS: Micro-organisms were detected in 68 of 80 explanted components. The highest bacterial load was detected on the polyethylene liners, showing a significant difference in distribution of CFU between the liner and metal components (stem and cup). Staphylococcus epidermidis was identified as the pathogen causing the highest CFU count, especially from the polyethylene liner. CONCLUSIONS: Results of our study confirm that sonicate culture of the retrieved liners and heads, which revealed the highest bacterial loads, are reliable and sufficient for pathogen detection in the clinical diagnostic routine.

Strains on the human femur after revision total knee arthroplasty: An in vitro study using digital image correlation.

Pain at the tip of the stem of a knee prosthesis (End-of-Stem Pain) is a common problem in revision total knee arthroplasty (TKA). It may be caused by a problematic interaction between stem and bone, but the exact biomechanical correlate is still unknown. On top of this, there is no biomechanical study investigating End-of-Stem Pain at the distal femur using human specimens. Aim of this study was to find out whether the implantation of a revision total knee implant leads to high femoral surface strains at the tip of the stem, which the authors expect to be the biomechanical correlate of End-of-Stem Pain. We implanted 16 rotating hinge knee implants into 16 fresh-frozen human femora using the hybrid fixation technique and comparing two reaming protocols. Afterwards, surface strains on these femora were measured under dynamic load in two different load scenarios (climbing stairs and chair rising) using digital image correlation (DIC) and fracture patterns after overcritical load were analysed. Peak surface strains were found at the tip of the stem in several measurements in both load scenarios. There were no significant differences between the two compared groups (different trial sizes) regarding surface strains and fracture patterns. We conclude that implantation of a long intramedullary stem in revision TKA can lead to high surface strains at the tip of the stem that may be the correlate of femoral End-of-Stem Pain. This finding might allow for a targeted development of future stem designs that can lead to lower surface strains and therefore might reduce End-of-Stem Pain. Digital Image Correlation proved valid for the measurement of surface strains and can be used in the future to test new stem designs in vitro.

1st EFORT European Consensus "Medical & Scientific Research Requirements for the Clinical Introduction of Artificial Joint Arthroplasty Devices": Background, Delphi Methodology & Consensus process.

The objectives of the 1st EFORT European Consensus on 'Medical and Scientific Research Requirements for the Clinical Introduction of Artificial Joint Arthroplasty Devices' were foremost to focus on patient safety by establishing performance requirements for medical devices. The 1st EFORT European Consensus applied an a priori-defined, modified Delphi methodology to produce unbiased, high-quality recommendation statements, confirmed by consensus voting of a European expert panel. Intended key outcomes are practical guidelines justified by the current stage of knowledge and based on a broad European Expert Consensus, to maintain innovation and optimisation of orthopaedic devices within the boundaries of MDR 2017/745. Twenty-one main research areas of relevance were defined relying on input from the EFORT IPSI WG1 'Introduction of Innovation' recommendations and a related survey. A modified Delphi approach with a preparatory literature review and work in small groups were used to prepare answers to the research questions in the form of 32 draft Consensus statements. A Consensus Conference in a hybrid format, on-site in the Carl Gustav Carus University of Dresden was organised to further refine the draft statements and define consensus within the complete group of participants by final voting, intended to further quantify expert opinion knowledge. The modified Delphi approach provides practical guidelines for hands-on orientation for orthopaedic surgeons, research institutes and laboratories, orthopaedic device manufacturers, patient representatives, Notified Bodies, National Institutes and authorities. For the first time, initiated by the EFORT IPSI (WG1 'Introduction of Innovation'), knowledge of all related stakeholders was combined in the 1st EFORT European Consensus to develop guidelines and result in a comprehensive set of recommendations.

Long Term Results of a Rotating Hinge Total Knee Prosthesis With Carbon-Fiber Reinforced Poly-Ether-Ether-Ketone (CFR-PEEK) as Bearing Material.

Background: The use of rotating hinge (RH) prostheses for severe primary as well as revision arthroplasty is widely established. Due to the steadily increasing number of RH prostheses, we aimed to assess the complication frequencies, complication types and clinical outcomes of a modern RH hinge prosthesis using a new bearing material with a minimum follow-up of 7 years. Methods: Fifty-six consecutive patients who received the EnduRo® RH prosthesis using carbon-fiber reinforced poly-ether-ether-ketone (CFR-PEEK) as bearing material were included in this prospective study: 21 patients (37.5%) received the prosthesis as a primary total knee arthroplasty (TKA) and 35 patients (62.5%) underwent revision total knee arthroplasties (rTKA). Clinical and radiographic examinations were performed preoperatively, postoperatively after three and 12 months and annually thereafter. Clinical scores were documented for each patient. Competing risk analysis was assessed with respect to indication and failure mode. Results: Knee Society Score (KSS), Western Ontario and McMaster Osteoarthritis Index (WOMAC), Oxford Knee Score (OKS) and range of motion (ROM) improved significantly compared to preoperative values (p < 0.0001). The overall cumulative incidence for revision surgery was 23.6% at 7 years and the cumulative incidence for complications associated with failure of the prothesis was 5.6% at 7 years, respectively. Complications occurred more frequently in the revision group (p = 0.002). Conclusion: The evaluated RH prosthesis provided reliable and durable results for a minimum follow-up of 7 years. Prosthesis survival was successful considering the complexity of the cases. The use of this RH system in primary patients showed high survival rates and long-term functional outcomes and clinical outcomes proved to be satisfying in both revision and primary cases. No adverse events were associated with the new bearing material CFR-PEEK.

Biomechanical Effects of Stemmed Total Knee Arthroplasty on the Human Femur: A CT-Data Based Study.

End-of-stem pain of the femur is a common problem in revision total knee arthroplasty (TKA). It may be caused by a problematic interaction between stem and bone, but the exact biomechanical correlate is still unknown. The aim of this prospective study was to find out how the stem is positioned in the medullary canal, how the femoral geometry changes due to implantation, and whether the results are influenced by the diameter of the trial. We implanted 16 rotating hinge knee implants into 16 fresh-frozen human femora using the hybrid fixation technique and comparing two reaming protocols. We created 3-dimensional models of the specimens before and after implantation using CT-scans and calculated the differences. The main contact between stem and bone was found at the proximal 30 mm of the stem, especially anterior. We observed two different contact patterns of stem and bone. The cortical thickness was reduced especially at the anterior tip of the stem with a maximum reduction of 1405 ± 501 µm in the standard group and 980 ± 447 µm in the small_trial group, which is a relative reduction of 34 ± 14% (standard group) and 26 ± 14% (small_trial group). The bone experienced a deformation to posterior and lateral. We conclude that the tip of the stem is an important biomechanical region. Different contact patterns between stem and bone as well as the reduction in cortical thickness at the tip of the stem may play a role in the development of end-of-stem pain.

Total hip replacement in congenital high hip dislocation following iliofemoral monotube distraction.

The aim of this study was to prospectively evaluate our single-centre one- and five-year results of anatomically correct cementless total hip arthroplasty in unilateral and bilateral Crowe type IV high hip dislocations in ten hips following iliofemoral monotube soft tissue distraction. Six consecutive patients (five females and one male) with unilateral and two female patients with bilateral high hip dislocation with an average age of 46 years and height of dislocation up to 110 mm were treated in our institution. Limb lengthening was achieved up to 100 mm. The mean leg-length-discrepancy was -4 mm postoperatively. Harris hip score increased significantly at one year (p < 0.001) and significantly further (p < 0.05) at five years postoperative. WOMAC, VAS pain scale as well as gait and pain-free walking distance also improved significantly at follow-up. Two pin infections and one temporary peroneal nerve palsy occurred during monotube extension. Three cup protrusions that required revision surgery were observed in two patients. This study shows that iliofemoral distraction prior to total hip replacement achieves leg length equality and improved gluteal function and therefore gait in patients with Crowe type IV hip dislocation.

Microarray analysis identifies distinct gene expression profiles associated with histological subtype in human osteosarcoma.

Osteosarcoma is the most common primary malignant bone tumour. Currently osteosarcoma classification is based on histological appearance. It was the aim of this study to use a more systematic approach to osteosarcoma classification based on gene expression analysis and to identify subtype specific differentially expressed genes. We analysed the global gene expression profiles of ten osteosarcoma samples using Affymetrix U133A arrays (five osteoblastic and five non-osteoblastic osteosarcoma patients). Differential gene expression analysis yielded 75 genes up-regulated and 97 genes down-regulated in osteoblastic versus non-osteoblastic osteosarcoma samples, respectively. These included genes involved in cell growth, chemotherapy resistance, angiogenesis, steroid- and neuropeptide hormone receptor activity, acute-phase response and serotonin receptor activity and members of the Wnt/ß-catenin pathway and many others. Furthermore, we validated the highly differential expression of six genes including angiopoietin 1, IGFBP3, ferredoxin 1, BMP, decorin, and fibulin 1 in osteoblastic osteosarcoma relative to non-osteoblastic osteosarcoma. Our results show the utility of gene expression analysis to study osteosarcoma subtypes, and we identified several genes that may play a role as potential therapeutic targets in the future.

No effect in primary stability after increasing interference fit in cementless TKA tibial components.

Cementless total knee arthroplasty (TKA) implants rely on interference fit to achieve initial stability. However, the optimal interference fit is unknown. This study investigates the effect of using different interference fit on the initial stability of tibial TKA implants. Experiments were performed on human cadaveric tibias using a low interference fit of 350 µm of a clinically established cementless porous-coated tibial implant and a high interference fit of 700 µm. The Orthoload peak loads of gait and squat were applied to the specimens with a custom-made load applicator. Micromotions and gaps opening/closing were measured at the bone-implant interface using Digital Image Correlation (DIC) in 6 regions of interest (ROIs). Two multilevel linear mixed-effect models were created with micromotions and gaps as dependent variables. The results revealed no significant differences for micromotions between the two interference fits (gait p = 0.755, squat p = 0.232), nor for gaps opening/closing (gait p = 0.474, squat p = 0.269). In contrast, significant differences were found for the ROIs in the two dependent variables (p < 0.001), where more gap closing was seen in the posterior ROIs than in the anterior ROIs during both loading configurations. This study showed that increasing the interference fit from 350 to 700 µm did not influence initial stability.

N-Glycan profiling of chondrocytes and fibroblast-like synoviocytes: Towards functional glycomics in osteoarthritis.

PURPOSE: N-Glycan profiling provides an indicator of the cellular potential for functional pairing with tissue lectins. Following the discovery of galectin expression by chondrocytes as a factor in osteoarthritis pathobiology, mapping of N-glycans upon their phenotypic dedifferentiation in culture and in fibroblast-like synoviocytes is a step to better understand glycobiological contributions to disease progression. EXPERIMENTAL DESIGN: The profiles of cellular N-glycans of human osteoarthritic chondrocytes and fibroblast-like synoviocytes were characterized by mass spectrometry. RT-qPCR experiments determined mRNA levels of 16 glycosyltransferases. Responsiveness of cells to galectins was quantified by measuring the mRNA level for interleukin-1ß. RESULTS: The shift of chondrocytes to a fibroblastic phenotype (dedifferentiation) is associated with changes in N-glycosylation. The N-glycan profile of chondrocytes at passage 4 reflects characteristics of synoviocytes. Galectins-1 and -3 enhance expression of interleukin-1ß mRNA in both cell types, most pronounced in primary culture. Presence of interleukin-1ß leads to changes in sialylation in synoviocytes that favor galectin binding. CONCLUSIONS AND CLINICAL RELEVANCE: N-Glycosylation reflects phenotypic changes of osteoarthritic cells in vitro. Like chondrocytes, fibroblast-like synoviocytes express N-glycans that are suited to bind galectins, and these proteins serve as inducers of pro-inflammatory markers in these cells. Synoviocytes can thus contribute to disease progression in osteoarthritis in situ.

The effect of different interference fits on the primary fixation of a cementless femoral component during experimental testing.

Cementless femoral total knee arthroplasty (TKA) components use a press-fit (referred to as interference fit) to achieve initial fixation. A higher interference fit could lead to a superior fixation, but it could also introduce more damage to the bone during implantation. The purpose of the current study was to investigate the effect of interference fit on the micromotions and gap opening/closing at the bone-implant interface. Experimental tests were performed in six pairs of cadaveric femurs implanted with femoral components using a low interference fit of 350 µm and a high interference fit of 700 µm. The specimens were subjected to the peak loads of gait and squat, based on the Orthoload dataset. Digital Image Correlation (DIC) was used to measure the micromotions and opening/closing in different regions of interest (ROIs). Two linear mixed-effect statistical models were created with micromotions and gap opening/closing as dependent variables. ROIs, loading conditions, and implant designs as independent variables, and cadaver specimens as random intercepts. The results revealed no significant difference between the two interference fit implants for micromotions (p = 0.837 for gait and p = 0.065 for squat), nor for the gap opening/closing (p = 0.748 for gait and p = 0.561 for squat). In contrast, significant differences were found between loading and most of the ROIs in both dependent variables (p < 0.0001). Additionally, no difference in bone deformation was found between low and high interference fit. Changing interference between either 350 µm or 700 µm did not affect the primary stability of a femoral TKA component. There could be an interference fit threshold beyond which fixation does not further improve.

Total Hip Arthroplasty Using Imageless Computer-Assisted Navigation-2-Year Follow-Up of a Prospective Randomized Study.

The purpose of this study is to compare computer-assisted to manual implantation-techniques in total hip arthroplasty (THA) and to find out if the computer-assisted surgery is able to improve the clinical and functional results and reduce the dislocation rate in short-terms after THA. We performed a concise minimum 2-year follow-up of the patient cohort of a prospective randomized study published in 2014 and evaluated if the higher implantation accuracy in the navigated group can be seen as an important determinant of success in total hip arthroplasty. Although a significant difference was found in mean postoperative acetabular component anteversion and in the outliers regarding inclination and anteversion (p < 0.05) between the computer-assisted and the manual-placed group, we could not find significant differences regarding clinical outcome or revision rates at 2-years follow-up. The implantation accuracy in the navigated group can be regarded as an important determinant of success in THA, although no significant differences in clinical outcome could be detected at short-term follow-up. Therefore, further long-term follow-up of our patient group is needed.

High Revision Rates of a Cementless Beta-Titanium Alloy Stem with Contamination-Free Roughened Surface in Primary Total Hip Arthroplasty.

Optimal osseointegration of cementless total hip arthroplasty is essential for high stability and long-term survival. The purpose of this follow-up study was to evaluate the clinical and radiological outcome, the complications, and survival rates of a beta-titanium alloy stem with a specific grit-blasted-free surface. In 192 patients (mean age of 64.4 years), 202 consecutive primary total hip arthroplasties were performed using a cementless Hipstar® stem (Stryker, Duisburg, DE). The Harris Hip Score (HHS) was assessed pre-operatively and post-operatively. Radiolucent lines were evaluated and the implant survival rate was calculated using Kaplan-Meier analysis. The mean follow-up was 7.71 years (range of 5.0-14.0 years). Overall, 15 revisions were performed. Early aseptic stem loosening was observed in six cases (2.97%). Radiolucent-lines adjacent to the stem were detected in 73 cases (83.02%), especially (70.46%) in the Gruen zones 1, 7, 8, and 14. The mean postoperative HHS was 92.65 points (range 42-100). The cumulative survival probability of the stem was 94.4% (95% CI 90.3 to 98.5%). Considering aseptic failure as an endpoint, the cumulative survival rate of the stem was 95.3% (95% CI 0.914 to 0.992) at six years of follow-up. Overall, an inferior mid-term implant survival was observed in comparison to well-established cementless stem designs.

Learning curve in navigated total knee replacement. A multi-centre study comparing experienced and beginner centres.

This study analyzes the OrthoPilot navigation system's (Aesculap, Tuttlingen, FRG) learning curve in beginner vs. experienced centres. We conducted a prospective, controlled, multi-centre study in 13 European orthopedic centres. Overall, 368 total knee replacements (TKR) were included in this study, with 150 TKR performed in experienced centres (control group) and 218 TKR in beginner centres (study group). The study parameters were implantation accuracy, clinical outcome, operation time and complications. No difference was found between both groups, except for operating time which was significantly longer in the study group. However, this increase in operating time disappeared after 30 implantations in all beginner centres. So, we conclude that the system's learning curve levels off at this point. Given the high accuracy of implantation when using the OrthoPilot navigation system, we believe this learning curve to be acceptably low.

How Accurate is Intraoperative Alignment Measurement with a Navigation System in Primary Total Knee Arthroplasty?

The primary objective was to compare the intraoperative data assessed by OrthoPilot (Aesculap AG, Tuttlingen, Germany) with postoperative coronal and sagittal long-leg standing radiographs. The secondary objective was to evaluate the influence of sex and body mass index (BMI) on the accuracy and effectiveness of the implantation of the knee prosthesis by OrthoPilot. We included 75 patients in our investigation. Participants received an e.motion (Aesculap AG) knee prosthesis using the OrthoPilot navigation system. Postoperative long-leg standing anteroposterior and lateral radiographs were performed. We compared the intraoperative navigational data with postoperative determined angles of knee geometry. We also compared the sex and BMI of participants to their difference between intraoperative and postoperative measurements to test for an association. We found a difference between intraoperative data and radiographs of 1.8 degrees for the hip-knee-ankle angle. The intraoperative lateral distal femoral angle and medial proximal tibial angle differed from the radiological analysis by 1.2 degrees, respectively. The lateral views revealed a difference of 1.6 degrees for femur lateral and 1.4 degrees for the tibia lateral. There was no significant (p > 0.05) influence of the parameters BMI and sex of the patients on these values. Our results showed that the implemented intraoperative navigation system is reliable. It does not differ on average from postoperative radiographs by more than 1.8 degrees. The findings of our study suggest that a correct postoperative alignment can be achieved in both high and low BMI participants if a precise range is maintained during the surgery.

Vascular Morphogenesis in the Context of Inflammation: Self-Organization in a Fibrin-Based 3D Culture System.

Introduction: New vessel formation requires a continuous and tightly regulated interplay between endothelial cells with cells of the perivascular microenvironment supported by mechanic-physical and chemical cues from the extracellular matrix. Aim: Here we investigated the potential of small fragments of synovial tissue to form de novo vascular structures in the context of inflammation within three dimensional (3D) fibrin-based matrices in vitro, and assessed the contribution of mesenchymal stromal cell (MSC)-immune cell cross-talk to neovascularization considering paracrine signals in a fibrin-based co-culture model. Material and Methods: Synovial tissue fragments from patients with rheumatoid arthritis (RA) and inflammatory osteoarthritis (OA) were cultivated within 3D fibrin matrices for up to 4 weeks. Cellular and structural re-arrangement of the initially acellular matrix were documented by phase contrast microscopy and characterized by confocal laser-scanning microscopy of topographically intact 3D cultures and by immunohistochemistry. MSC-peripheral blood mononuclear cell (PBMC) co-cultures in the 3D fibrin system specifically addressed the influence of perivascular cell interactions to neo-vessel formation in a pro-inflammatory microenvironment. Cytokine levels in the supernatants of cultured explant tissues and co-cultures were evaluated by the Bio-Plex cytokine assay and ELISA. Results: Vascular outgrowth from the embedded tissue into the fibrin matrix was preceded by leukocyte egress from the tissue fragments. Neo-vessels originating from both the embedded sample and from clusters locally formed by emigrated mononuclear cells were consistently associated with CD45+ leukocytes. MSC and PBMC in co-culture formed vasculogenic clusters. Clusters and cells with endothelial phenotype emerging from them, were surrounded by a collagen IV scaffold. No vascular structures were observed in control 3D monocultures of PBMC or MSC. Paracrine signals released by cultured OA tissue fragments corresponded with elevated levels of granulocyte-colony stimulating factor, vascular endothelial growth factor and interleukin-6 secreted by MSC-PBMC co-cultures. Conclusion: Our results show that synovial tissue fragments with immune cell infiltrates have the potential to form new vessels in initially avascular 3D fibrin-based matrices. Cross-talk and cluster formation of MSC with immune cells within the 3D fibrin environment through self-organization and secretion of pro-angiogenic paracrine factors can support neo-vessel growth.

Long-term follow-up of metal-on-metal total hip replacement.

Metal-on-metal articulations were reintroduced to reduce polyethylene particle-induced osteolysis. Elevated serum metal levels have been detected at short- and intermediate-term follow-up. There is little knowledge about long-term effects of increased ionic metal generation. Our study was undertaken to provide information about long-term survival, clinical outcome, radiographic appearance, and serum metal concentrations after a minimum 10 years follow-up with a metal-on-metal hip prosthesis: 105 cementless primary total hip prostheses with metal-on-metal articulating surfaces were implanted in 98 patients with a mean age of 56 years. Clinical data, radiographs, and blood samples were obtained at a follow-up visit 10 years after implantation. Serum cobalt and chromium levels were determined with use of atomic absorption spectrometry. General laboratory analyses included a full blood count and kidney function parameters. The Harris score was 92 points and the UCLA score 6 points after 10 years. Small osteolytic lesions and radiolucent lines were found in Gruen's zones 1, 7, 8, and 14. The probability of survival was 98.6%. The median serum cobalt concentration of the 22 patients with their hip replacement as the only source of cobalt was 0.75 microg/L (range, 0.3-50.1 microg/L). No patient was diagnosed with renal insufficiency during the study period. Five patients were diagnosed with a malignancy between surgery and the follow-up. We do not have evidence of an increased rate of primary malignancies nor could we detect renal failure in our study group. Serum metal levels did not differ from short- and intermediate term follow-up values.