Georg Köster

Phagocytosis of wear debris by osteoblasts affects differentiation and local factor production in a manner dependent on particle composition

Wear debris is considered to be one of the main factors responsible for aseptic loosening of orthopaedic endoprostheses. Whereas the response of cells in the monocytic lineage to foreign materials has been extensively studied, little is known about cells at the bone formation site. In the present study, we examined the hypothesis that the response of osteoblasts to wear debris depends on the chemical composition of the particles. We produced particles from commercially pure titanium (cpTi), Ti-6Al-4V (Ti-A), and cobalt-chrome (CoCr) and obtained ultrahigh molecular weight polyethylene (UHMWPE; GUR 4150) particles from a commercial source. The equivalent circle diameters of the particles were comparable: 1.0 +/- 0.96 microm for UHMWPE; 0.84 +/- 0.12 microm for cpTi; 1.35 +/- 0.09 microm for Ti-A, and 1.21 +/- 0.16 microm for CoCr. Confluent primary human osteoblasts and MG63 osteoblast-like cells were incubated in the presence of particles for 24 h. Harvested cultures were examined by transmission electron microscopy to determine if the cells had phagocytosed the particles. Particles were found intracellularly, primarily in the cytosol, in both the primary osteoblasts and MG63 cells. The chemical composition of the particles inside the cells was confirmed by energy-dispersive X-ray analysis. Morphologically, both cell types had extensive ruffled cell membranes, less-developed endoplasmic reticulum, swollen mitochondria, and vacuolic inclusions compared with untreated cells. CpTi, Ti-A, and CoCr particles were also added to cultures of MG63 cells to assess their effect on proliferation (cell number) and differentiation (alkaline phosphatase activity), and PGE2 production. All three types of particles had effects on the cells. The effect on cell number was dependent on the chemical composition of the particles; Ti-A and CoCr caused a dose-dependent increase, while cpTi particles had a biphasic effect with a maximal increase in cell number observed at the 1:10 dilution. Alkaline phosphatase specific activity was also affected and cpTi was more inhibitory than Ti-A or CoCr. PGE2 production was increased by all particles, but the magnitude of the effect was particle-dependent: CoCr > cpTi > Ti-A. This study demonstrates clearly that human osteoblast-like cells and MG63 cells can phagocytose small UHMWPE, CoCr, Ti-A, and cpTi particles. Phagocytosis of the particles is correlated with changes in morphology, and analysis of MG63 response shows that cell proliferation, differentiation, and prostanoid production are affected. This may have negative effects on bone formation adjacent to an orthopaedic implant and may initiate or contribute to the cellular events that cause aseptic loosening by inhibiting bone formation. The effects on alkaline phosphatase and PGE2 release are dependent on the chemical composition of the particles, suggesting that both the type and concentration of wear debris at an implant site may be important in determining clinical outcome.

Ceramic and PMMA particles differentially affect osteoblast phenotype.

There is increasing evidence that wear debris particles present in periprosthetic tissues have direct effects on osteoblasts. The nature of the cell response varies with the chemistry of the particle and the number of particles. Most studies have used Ti, Ti-6Al-4V, and ultrahigh molecular weight polyethylene (UHMWPE) particles since these materials are most frequently used in implants and as a result, these particles predominate in peri-prosthetic tissues. Ceramics have also been used successfully as load-bearing surfaces in implants for years, although it is unknown how wear debris from these surfaces may contribute to aseptic bone loss. Further, particles resulting from polymethylmethacrylate (PMMA) cements used for fixation may also be involved in aseptic loosening of implants, but how these particles may affect bone formation is unknown. In the present study, we examined whether aluminum oxide (Al2O3), zirconium oxide (ZrO2), and PMMA particles exert effects on osteoblast proliferation, phenotypic expression, and local factor production, and if so, whether the effects were specific to the particle type. ZrO2 particles were produced in a custom-made axial mixer in which ZrO2 containers were filled with ZrO2 bars and 95% ethanol and then rotated continuously at room temperature. PMMA particles were prepared in a ZrO2 roller mill. Al2O3 was produced and provided by Aesculap AG. Particles were endotoxin-free with equivalent circle diameters <3 microm; Al2O3 particles were significantly smaller than ZrO2 or PMMA particles. Particle suspensions were added to confluent cultures of MG63 osteoblast-like cells after diluting them 1:100, 1:10, and 1:1 with culture medium. Cells were incubated with the particles for 24 h. Transmission electron microscopy showed that MG63 cells phagocytosed Al2O3 particles and exhibited ultrastructural changes consistent with cytotoxicity. This was supported by biochemical changes as well. Proliferation, alkaline phosphatase activity, and TGF-beta1 levels were decreased. ZrO2 and PMMA particles increased proliferation and alkaline phosphatase specific activity. The effect of ZrO2 on alkaline phosphatase was targeted to matrix vesicles, the effect of PMMA was greater on the cells. All particles increased prostaglandin E2 production. These results show that Al2O3, ZrO2, and PMMA particles elicit direct effects on osteoblasts and that cell response depends on the particle type. None of the particles tested had the same effect as noted previously for UHMWPE: increased proliferation and decreased alkaline phosphatase. These results may indicate that the response of peri-prosthetic tissues to wear particles may be modulated by the relative contributions of the various particle types present.

Tissue response and osteoinduction of human bone grafts in vivo

Abstract Freeze-dried human bone allograft is used clinically as an adjunct to autologous bone graft. When freeze-dried human bone allograft is demineralized, the allograft is osteoinductive, since it causes bone to form heterotopically. Both types of allograft are also used alone, such as in spinal fusions, critical size defects, and periodontal therapy. The purpose of this study was to determine the effect of demineralization on the osteoinductive potential of human bone grafts obtained from two different groups of patients. One group consisted of six patients younger than 42 years of age, while the other group consisted of six patients who were older than 70 years of age. The harvested material was lyophilized and divided into two portions, one of which was used directly while the other was demineralized. Osteoinductive ability was established using an in vivo assay for heterotopic bone formation. Activity in these bone grafts was compared with a batch of commercially prepared demineralized, freeze-dried human bone grafts that had been previously shown to be active and another batch that had been shown to display low (‘inactive’) osteoinductive ability. A bone induction score was determined for each group of grafts based on the number and size of any ossicles formed. In addition, the area of new bone formation and area of residual particles were determined histomorphometrically. Tissue response to the bone grafts varied with donor age and whether the samples had been demineralized or not. Only demineralized, freeze-dried bone graft from patients younger than 42 years of age was osteoinductive; all other batches displayed little or no osteoinductive activity. In the demineralized, freeze-dried bone from donors younger than 42 years of age, the bone induction score and new bone area were significantly higher than in the other batches of bone graft, and the area of residual particles was reduced. Both demineralized and nondemineralized bone graft from patients older than 70 years of age were encapsulated in dense, fibrous connective tissue. These results may help explain the observed differences in clinical outcome when demineralized, freeze-dried bone graft or nondemineralized, freeze-dried bone graft from different donors is used in bone regeneration applications.

An oblong revision cup for large acetabular defects: Design rationale and two- to seven-year follow-up

Loosening and migration of acetabular components often lead to extensive bony defects with an elongated, oval acetabular cavity. In these cases standard implants will not reestablish and maintain sufficient stability without leaving bone defects or using massive bone grafts or excess cement and additional metal rings or shells, disadvantages that are overcome by using an oblong revision cup without cement. The titanium shell is available in different sizes, is screwed to the autochthonous acetabular bone and houses an oblong polyethylene inlay, designed to reestablish the normal anatomic hip center. Of 109 consecutive revision cups, 102, implanted for American Academy of Orthopaedic Surgeons (AAOS) defects types I-IV, were followed up clinically and radiologically for 2 to 7 years (mean, 3.6 years). Primary stability was achieved in all cases. In 40% no bone grafting was necessary at all. The radiological follow-up revealed good remodeling of the surrounding bone and osseointegration of the implants. Zonal radiolucent lines, always smaller than 2 mm, were seen in 18 cases, only once completely and in only 5 cases partially progressing. Six cups migrated slightly (< or =2 mm), two moderately (3-5 mm), all without clinical symptoms, and two more than 5 mm. Migration and radiolucencies were mainly seen in patients with allografts and major defects, which indicates that bone ingrowth appears more unlikely in such cases. Few asymptomatic cases showed zonal sclerotic lines. There were two aseptic loosenings, one in a case with pelvic discontinuity, the other in a patient with severe rheumatoid arthritis following two previous revisions. Survivorship analysis based on implant removal because of aseptic loosening as the endpoint shows a cumulative success rate of 98.1% at 8 years.

Five- to 10-Year Results Using a Noncemented Modular Revision Stem Without Bone Grafting

The aim of the study was to evaluate the 5- to 10-year results (mean, 6.2 years) of a modular uncemented revision stem (Profemur-R). From a total series of 184 consecutive stem revisions, the first 73 were evaluated. The implant was fixed without bone grafting in all cases. The average Harris hip score increased from 40 to 75. A complete remodeling of bone defects could be documented radiographically in 70% of the cases and a partial restoration in 30%. Progressive subsidence appeared in 2 stems. Three rerevisions were required, including 1 septic case. The survival rate with aseptic loosening as the end point was 96% over an average of 10 years. The revision prosthesis examined in this study can be considered a viable and useful option to reconstruct femoral defects in revision hip arthroplasty.

Endoscopy of the femoral canal in revision arthroplasty of the hip

Abstract Femoral endoscopy using a special endoscope was performed in 28 revision arthroplasties with the aim of improving the operative technique and to analyze implant failure. Before clinical application, the method was used to analyze the implant bed in clinically and radiographically well-fixed prostheses in autopsy cases without implant failure. Initially, it was performed on 4 experimental implantations of newly designed revision devices into cadaver femurs to obtain additional information concerning the design rationale of implants and instruments for revision surgery. During revision surgery, the new endoscope showed that controlled removal of the cement and granulomatous tissue was possible while avoiding cortical windows or transfemoral approaches. Under visual control, preparation of the new implant bed was less hazardous and more efficient, resulting in good preservation of bone stock and reduced exposure to X-rays. Analysis of the implant bed in failed hip endoprostheses revealed cracks or fractures of the cement mantle in 21 of 23 cemented components. There were two different types of cracks: longitudinal and transverse, which were mostly connected and invisible to X-ray analysis. Cement defects, thin cement mantles, or the proximal border of the cement mantle were found to be places where cracks originated. Granulomatous tissue was noted to protrude into the cement fissures and cracks. In autopsy cases, cement cracks were also found in clinically asymptomatic and radiographically well-fixed prostheses. These cracks were observed to be mainly oriented in the longitudinal direction, similar to those seen in the revision cases. Early signs of debonding became obvious even without lesions in the cement mantle. In experimental implantations of newly designed stems, the efficacy of the different instruments and the fit of the implant could be evaluated by endoscopic control inside the intramedullary canal. Further, it was possible to directly visualize the shape and condition of the primary implant bed after removal of the implant. Femoral endoscopy improved the surgical technique in revision arthroplasty. In addition, it is a very useful tool for the analysis of the implant bed in clinical and autopsy cases as well as in experimental implantations.

Effect of polymer molecular weight and addition of calcium stearate on response of MG63 osteoblast-like cells to UHMWPE particles

Periprosthetic osteolysis and implant loosening is associated with the presence of ultrahigh molecular weight polyethylene (UHMWPE) wear debris particles. Osteoblast phenotypic expression in vitro is affected by UHMWPE particles, suggesting that bone formation may also be affected by wear debris. Here we tested the hypothesis that the response of osteoblasts to UHMWPE can be modified by changes in UHMWPE particle chemistry. We used four different commercially available preparations of GUR UHMWPE particles to determine if chemical composition (±Ca‐stearate) or polymer molecular weight (3.1–4.2 million or 5.4–6.5 million g/mol) modulates osteoblast response. Particles were characterized by size distribution, morphology, and number of particles added to the culture medium. They had an average equivalent circle diameter ranging from 0.46–1.26 μm. MG63 cell response was assessed by measuring cell number, cellular and cell layer alkaline phosphatase, and prostaglandin E2 (PGE2) production. There were dose‐dependent effects of the particles on cell response. Cell number and PGE2 production were increased, while alkaline phosphatase specific activity was decreased. In addition, there was a marked difference between cultures treated with particles containing Ca‐stearate and as a function of polymer molecular weight. Particles of higher molecular weight caused a greater stimulation of proliferation and inhibition of alkaline phosphatase than particles of lower molecular weight. The presence of Castearate exerted a more pronounced depression of osteoblast phenotype as well as a significantly greater increase in PGE2 release by the cells. The present study shows that chemical composition and polymer molecular weight of UHMWPE are capable of modulating osteoblast response to particles. The results suggest that osteoblast differentiation is inhibited by UHMWPE particles, whereas cell proliferation and PGE2 production are stimulated. This may have direct effects on osteoblasts and bone formation, but also paracrine effects on cells of the monocytic lineage inducing bone resorption and promoting inflammation which may lead to aseptic loosening. The present results suggest that the cellular events in aseptic loosening may be modulated or even accelerated by changes in the composition of the UHMWPE used to fabricate implants.

Giant synovial osteochondromatosis of the acromio-clavicular joint in a child. A case report and review of the literature.

Primary intra-articular synovial chondromatosis represents an uncommon condition involving mainly the large joints predominantly of middle-aged adults. We herein document the first case of synovial chondromatosis affecting the acromio-clavicular joint of a 10-year-old girl, characterized by a solitary huge intra-articular osteochondromatous body (giant synovial chondromatosis) that had caused dislocation and deformation of the lateral portion of the clavicle. Successful surgical treatment consisted of removal of the osteochondral body and replacement of the clavicle by fixation with a K-wire.

Centralization of the femoral component in cemented hip arthroplasty using guided stem insertion

Abstract In order to improve the positioning of the stem within the femur, to centralize it within the cement and to achieve a complete and homogeneous cement mantle, a new hip endoprosthesis with guided stem insertion was developed. The femoral component has a longitudinal channel that takes up a guidewire which directs it during insertion into the centre. The guidewire is attached to the cement stopper which is positioned in the marrow cavity before applying the bone cement. The first 100 endoprostheses of this type with an observation period of at least 6 years were assessed radiologically and clinically. The clinical evaluation according to the hip scores of Merle d’Aubigne and Harris revealed a marked improvement between preoperative and postoperative values for all criteria. On radiological assessment 94% of the stems had a neutral position within the femur; 98% of the stems were found to be ideally centred within the cement distally, 80% distally and proximally; 74% of the cement cuffs had a complete and homogeneous cement layer between 2 and 5 mm medially and laterally, while 25% had partially a dimension of more than 5 mm, predominantly proximally. In only 3 cases was one part of the cement mantle found to be less than 2 mm. The radiological follow-up was also documented according to the delineated zones of Gruen. It revealed zonal radiolucent lines in 15 cases, combined in 11 cases with reactive lines, never extending up to 4 zones out of 14. Five prostheses had subsided moderately between 2 and 3 mm, and only one 8 mm. None of these radiological signs was associated with clinical symptoms. There were five cement fractures. Two stems were symptomatic, radiologically loose and revised. Beside these two cases of aseptic loosening there was one septic case, so that in total 97% of the implants are still functioning well.

Interface abrasion between rough surface femoral stems and PMMA cement results in extreme wear volumes--a retrieval study and failure analysis.

During the loosening cascade of cemented rough femoral stems, the destruction of the mantle and the production of cement and metal wear debris occur after the loss of constraint at the interface. Two-dimensional (2D) measurements (light microscopy based morphometry on fragments of mantles and vertical scanning interferometry of femoral stems) permitted mathematical 3D-extrapolations to estimate the wear volumes. Fragments of the cement mantles available lost volumes from 0.85 mm(3) to 494.10 mm(3) (median amount of bone cement wear = 178,426 mg). The harder metal surfaces lost between 1.459 mm(3) and 5.688 mm(3) of material (the median amount of metal wear per surface = 1.504 mg/100 mm(2)). Compared to the loss of material due to the fretting of stems, the abrasion of metal, and cement in defective cement mantles produced wear volumes sufficiently high to induce osteolysis. Though the design of the femoral stem and the handling of bone cement do not represent contemporary design and clinical practice, respectively, an extremely high number of joint replacements still in daily use may be impacted by this study because of possible predicted failures. Once the processes of fragmentation, abrasion, and osteolysis have been realized, the time until revision surgery should not be unduly prolonged.