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The Bone & Joint Journal
Vol. 102-B, Issue 11 | Pages 1527 - 1534
3 Nov 2020
Orita K Minoda Y Sugama R Ohta Y Ueyama H Takemura S Nakamura H

Aims. Vitamin E-infused highly cross-linked polyethylene (E1) has recently been introduced in total knee arthroplasty (TKA). An in vitro wear simulator study showed that E1 reduced polyethylene wear. However there is no published information regarding in vivo wear. Previous reports suggest that newly introduced materials which reduce in vitro polyethylene wear do not necessarily reduce in vivo polyethylene wear. To assist in the evaluation of the newly introduced material before widespread use, we established an in vivo polyethylene wear particle analysis for TKA. The aim of this study was to compare in vivo polyethylene wear particle generation between E1 and conventional polyethylene (ArCom) in TKA. Methods. A total of 34 knees undergoing TKA (17 each with ArCom or E1) were investigated. Except for the polyethylene insert material, the prostheses used for both groups were identical. Synovial fluid was obtained at a mean of 3.4 years (SD 1.3) postoperatively. The in vivo polyethylene wear particles were isolated from the synovial fluid using a previously validated method and examined by scanning electron microscopy. Results. The total number of polyethylene wear particles obtained from the knees with E1 (mean 6.9, SD 4.0 × 10. 7. counts/knee) was greater than that obtained from those with ArCom (mean 2.2, SD 2.6 × 10. 7. counts/knee) (p = 0.001). The particle size (equivalent circle of diameter) from the knees with E1 was smaller (mean 0.5 μm, SD 0.1) than that of knees with ArCom (mean 1.5, SD 0.3 μm) (p = 0.001). The aspect ratio of particles from the knees with E1 (mean 1.3, SD 0.1) was smaller than that with ArCom (mean 1.4, SD 0.1) (p < 0.001 ). Conclusion. This is the first report of in vivo wear particle analysis of E1. E1 polyethylene did not reduce the number of in vivo polyethylene wear particles compared with ArCom in early clinical stage. Further careful follow-up of newly introduced E1 for TKA should be carried out. Cite this article: Bone Joint J 2020;102-B(11):1527–1534


The Journal of Bone & Joint Surgery British Volume
Vol. 58-B, Issue 4 | Pages 496 - 503
1 Nov 1976
Stein H Yarom R Robin G Peters P Hall T Makin M

This study shows that after intra-articular injection, aurothiomalate and colloidal gold of small (200 A) particle size were rapidly absorbed from joints while the larger, 300 A, particle size colloidal radioactive gold could not be found outside them. Larger particle size suspensions seem therefore more likely to remain localised in the joint and its lining synovium after intra-articular injection, the systemic absorption from the joint cavity diminishing with increasing particle size. It was also found that the intra-articular injection of small amounts of aurothiomalate, of colloidal gold and of colloidal radioactive gold produces identical degenerative lesions in the lining cells of the proximal convoluted tubules of the kidneys. These lesions were always found, although gold particles were demonstrated only in sampled kidney tissues of the animals injected with the soluble gold preparation whereas no gold could be detected in the tissues of animals injected with colloidal non-radioactive or radioactive gold. Electron microscopic evidence is presented to suggest the possibility that the mitochondria are the "target" organelles of the gold-induced cellular damage. Mitochondrial damage was demonstrated in liver and spleen in addition to the already described kidney damage. The correlation between structure and function of the mitochondrial changes is not clear, and ionic shifts may be both a cause and a result of damage


The Bone & Joint Journal
Vol. 98-B, Issue 7 | Pages 925 - 933
1 Jul 2016
Sidaginamale RP Joyce TJ Bowsher JG Lord JK Avery PJ Natu S Nargol AVF Langton DJ

Aims. We wished to investigate the influence of metal debris exposure on the subsequent immune response and resulting soft-tissue injury following metal-on-metal (MoM) hip arthroplasty. Some reports have suggested that debris generated from the head-neck taper junction is more destructive than equivalent doses from metal bearing surfaces. . Patients and Methods. We investigated the influence of the source and volume of metal debris on chromium (Cr) and cobalt (Co) concentrations in corresponding blood and hip synovial fluid samples and the observed agglomerated particle sizes in excised tissues using multiple regression analysis of prospectively collected data. A total of 199 explanted MoM hips (177 patients; 132 hips female) were analysed to determine rates of volumetric wear at the bearing surfaces and taper junctions. . Results. The statistical modelling suggested that a greater source contribution of metal debris from the taper junction was associated with smaller aggregated particle sizes in the local tissues and a relative reduction of Cr ion concentrations in the corresponding synovial fluid and blood samples. Metal debris generated from taper junctions appears to be of a different morphology, composition and therefore, potentially, immunogenicity to that generated from bearing surfaces. Conclusion. The differences in debris arising from the taper and the articulating surfaces may provide some understanding of the increased incidence of soft-tissue reactions reported in patients implanted with MoM total hip arthroplasties compared with patients with hip resurfacings. Cite this article: Bone Joint J 2016;98-B:925–33


The Bone & Joint Journal
Vol. 98-B, Issue 12 | Pages 1662 - 1667
1 Dec 2016
Teoh KH von Ruhland C Evans SL James SH Jones A Howes J Davies PR Ahuja S

Aims. We present a case series of five patients who had revision surgery following magnetic controlled growing rods (MGCR) for early onset scoliosis. Metallosis was found during revision in four out of five patients and we postulated a mechanism for rod failure based on retrieval analysis. Patients and Methods. Retrieval analysis was performed on the seven explanted rods. The mean duration of MCGR from implantation to revision was 35 months (17 to 46). The mean age at revision was 12 years (7 to 15; four boys, one girl). Results. A total of six out of seven rods had tissue metallosis and pseudo-capsule surrounding the actuator. A total of four out of seven rods were pistoning. There were two rods which were broken. All rods had abrasive circumferential markings. A significant amount of metal debris was found when the actuators were carefully cut open. Analytical electron microscopy demonstrated metal fragments of predominantly titanium with a mean particle size of 3.36 microns (1.31 to 6.61). Conclusion. This study highlights concerns with tissue metallosis in MCGR. We recommend careful follow-up of patients who have received this implant. Cite this article: Bone Joint J 2016;98-B:1662–7


The Journal of Bone & Joint Surgery British Volume
Vol. 81-B, Issue 1 | Pages 118 - 124
1 Jan 1999
Brewster NT Gillespie WJ Howie CR Madabhushi SPG Usmani AS Fairbairn DR

In impaction grafting of contained bone defects after revision joint arthroplasty the graft behaves as a friable aggregate and its resistance to complex forces depends on grading, normal load and compaction. Bone mills in current use produce a distribution of particle sizes more uniform than is desirable for maximising resistance to shear stresses. We have performed experiments in vitro using morsellised allograft bone from the femoral head which have shown that its mechanical properties improve with increasing normal load and with increasing shear strains (strain hardening). The mechanical strength also increases with increasing compaction energy, and with the addition of bioglass particles to make good the deficiency in small and very small fragments. Donor femoral heads may be milled while frozen without affecting the profile of the particle size. Osteoporotic femoral heads provide a similar grading of sizes, although fewer particles are obtained from each specimen. Our findings have implications for current practice and for the future development of materials and techniques


Bone & Joint Research
Vol. 12, Issue 10 | Pages 636 - 643
10 Oct 2023
Hamilton V Sheikh S Szczepanska A Maskell N Hamilton F Reid JP Bzdek BR Murray JRD

Aims

Orthopaedic surgery uses many varied instruments with high-speed, high-impact, thermal energy and sometimes heavy instruments, all of which potentially result in aerosolization of contaminated blood, tissue, and bone, raising concerns for clinicians’ health. This study quantifies the aerosol exposure by measuring the number and size distribution of the particles reaching the lead surgeon during key orthopaedic operations.

Methods

The aerosol yield from 17 orthopaedic open surgeries (on the knee, hip, and shoulder) was recorded at the position of the lead surgeon using an Aerodynamic Particle Sizer (APS; 0.5 to 20 μm diameter particles) sampling at 1 s time resolution. Through timestamping, detected aerosol was attributed to specific procedures.


Bone & Joint Research
Vol. 12, Issue 10 | Pages 667 - 676
19 Oct 2023
Forteza-Genestra MA Antich-Rosselló M Ramis-Munar G Calvo J Gayà A Monjo M Ramis JM

Aims

Extracellular vesicles (EVs) are nanoparticles secreted by all cells, enriched in proteins, lipids, and nucleic acids related to cell-to-cell communication and vital components of cell-based therapies. Mesenchymal stromal cell (MSC)-derived EVs have been studied as an alternative for osteoarthritis (OA) treatment. However, their clinical translation is hindered by industrial and regulatory challenges. In contrast, platelet-derived EVs might reach clinics faster since platelet concentrates, such as platelet lysates (PL), are already used in therapeutics. Hence, we aimed to test the therapeutic potential of PL-derived extracellular vesicles (pEVs) as a new treatment for OA, which is a degenerative joint disease of articular cartilage and does not have any curative or regenerative treatment, by comparing its effects to those of human umbilical cord MSC-derived EVs (cEVs) on an ex vivo OA-induced model using human cartilage explants.

Methods

pEVs and cEVs were isolated by size exclusion chromatography (SEC) and physically characterized by nanoparticle tracking analysis (NTA), protein content, and purity. OA conditions were induced in human cartilage explants (10 ng/ml oncostatin M and 2 ng/ml tumour necrosis factor alpha (TNFα)) and treated with 1 × 109 particles of pEVs or cEVs for 14 days. Then, DNA, glycosaminoglycans (GAG), and collagen content were quantified, and a histological study was performed. EV uptake was monitored using PKH26 labelled EVs.


Bone & Joint Research
Vol. 13, Issue 1 | Pages 28 - 39
10 Jan 2024
Toya M Kushioka J Shen H Utsunomiya T Hirata H Tsubosaka M Gao Q Chow SK Zhang N Goodman SB

Aims

Transcription factor nuclear factor kappa B (NF-κB) plays a major role in the pathogenesis of chronic inflammatory diseases in all organ systems. Despite its importance, NF-κB targeted drug therapy to mitigate chronic inflammation has had limited success in preclinical studies. We hypothesized that sex differences affect the response to NF-κB treatment during chronic inflammation in bone. This study investigated the therapeutic effects of NF-κB decoy oligodeoxynucleotides (ODN) during chronic inflammation in male and female mice.

Methods

We used a murine model of chronic inflammation induced by continuous intramedullary delivery of lipopolysaccharide-contaminated polyethylene particles (cPE) using an osmotic pump. Specimens were evaluated using micro-CT and histomorphometric analyses. Sex-specific osteogenic and osteoclastic differentiation potentials were also investigated in vitro, including alkaline phosphatase, Alizarin Red, tartrate-resistant acid phosphatase staining, and gene expression using reverse transcription polymerase chain reaction (RT-PCR).


Bone & Joint Research
Vol. 12, Issue 1 | Pages 33 - 45
16 Jan 2023
Li B Ding T Chen H Li C Chen B Xu X Huang P Hu F Guo L

Aims

Circular RNA (circRNA) is involved in the regulation of articular cartilage degeneration induced by inflammatory factors or oxidative stress. In a previous study, we found that the expression of circStrn3 was significantly reduced in chondrocytes of osteoarthritis (OA) patients and OA mice. Therefore, the aim of this paper was to explore the role and mechanism of circStrn3 in osteoarthritis.

Methods

Minus RNA sequencing, fluorescence in situ hybridization, and quantitative real-time polymerase chain reaction (qRT-PCR) were used to detect the expression of circStrn3 in human and mouse OA cartilage tissues and chondrocytes. Chondrocytes were then stimulated to secrete exosomal miR-9-5p by cyclic tensile strain. Intra-articular injection of exosomal miR-9-5p into the model induced by destabilized medial meniscus (DMM) surgery was conducted to alleviate OA progression.


The Journal of Bone & Joint Surgery British Volume
Vol. 76-B, Issue 1 | Pages 60 - 67
1 Jan 1994
Shanbhag A Jacobs J Glant T Gilbert J Black J Galante J

Interfacial membranes collected at revision from 11 failed uncemented Ti-alloy total hip replacements were examined. Particles in the membranes were characterised by electron microscopy, microchemical spectroscopy and particle size analysis. Most were polyethylene and had a mean size of 0.53 micron +/- 0.3. They were similar to the particles seen in the base resin used in the manufacture of the acetabular implants. Relatively few titanium particles were seen. Fragments of bone, stainless steel and silicate were found in small amounts. Most of the polyethylene particles were too small to be seen by light microscopy. Electron microscopy and spectroscopic techniques are required to provide an accurate description of this debris


The Journal of Bone & Joint Surgery British Volume
Vol. 80-B, Issue 2 | Pages 340 - 344
1 Mar 1998
Besong AA Tipper JL Ingham E Stone MH Wroblewski BM Fisher J

Ultra-high-molecular-weight polyethylene (UHMWPE) components for total joint replacement generate wear particles which cause adverse biological tissue reactions leading to osteolysis and loosening. Sterilisation of UHMWPE components by gamma irradiation in air causes chain scissions which initiate a long-term oxidative process that degrades the chemical and mechanical properties of the polyethylene. Using a tri-pin-on-disc tribometer we studied the effect of ageing for ten years after gamma irradiation in air on the volumetric wear, particle size distribution and the number of particles produced by UHMWPE when sliding against a stainless-steel counterface. The aged and irradiated material produced six times more volumetric wear and 34 times more wear particles per unit load per unit sliding distance than non-sterilised UHMWPE. Our findings indicate that oxidative degradation of polyethylene after gamma irradiation in air with ageing produces more wear


Bone & Joint Research
Vol. 11, Issue 9 | Pages 652 - 668
7 Sep 2022
Lv G Wang B Li L Li Y Li X He H Kuang L

Aims

Exosomes (exo) are involved in the progression of osteoarthritis (OA). This study aimed to investigate the function of dysfunctional chondrocyte-derived exo (DC-exo) on OA in rats and rat macrophages.

Methods

Rat-derived chondrocytes were isolated, and DCs induced with interleukin (IL)-1β were used for exo isolation. Rats with OA (n = 36) or macrophages were treated with DC-exo or phosphate-buffered saline (PBS). Macrophage polarization and autophagy, and degradation and chondrocyte activity of cartilage tissues, were examined. RNA sequencing was used to detect genes differentially expressed in DC-exo, followed by RNA pull-down and ribonucleoprotein immunoprecipitation (RIP). Long non-coding RNA osteoarthritis non-coding transcript (OANCT) and phosphoinositide-3-kinase regulatory subunit 5 (PIK3R5) were depleted in DC-exo-treated macrophages and OA rats, in order to observe macrophage polarization and cartilage degradation. The PI3K/AKT/mammalian target of rapamycin (mTOR) pathway activity in cells and tissues was measured using western blot.


The Journal of Bone & Joint Surgery British Volume
Vol. 74-B, Issue 3 | Pages 380 - 384
1 May 1992
Lee J Salvati E Betts F DiCarlo E Doty S Bullough P

Reports of differing failure rates of total hip prostheses made of various metals prompted us to measure the size of metallic and polyethylene particulate debris around failed cemented arthroplasties. We used an isolation method, in which metallic debris was extracted from the tissues, and a non-isolation method of routine preparation for light and electron microscopy. Specimens were taken from 30 cases in which the femoral component was of titanium alloy (10), cobalt-chrome alloy (10), or stainless steel (10). The mean size of metallic particles with the isolation method was 0.8 to 1.0 microns by 1.5 to 1.8 microns. The non-isolation method gave a significantly smaller mean size of 0.3 to 0.4 microns by 0.6 to 0.7 microns. For each technique the particle sizes of the three metals were similar. The mean size of polyethylene particles was 2 to 4 microns by 8 to 13 microns. They were larger in tissue retrieved from failed titanium-alloy implants than from cobalt-chrome and stainless-steel implants. Our results suggest that factors other than the size of the metal particles, such as the constituents of the alloy, and the amount and speed of generation of debris, may be more important in the failure of hip replacements


The Journal of Bone & Joint Surgery British Volume
Vol. 81-B, Issue 3 | Pages 516 - 521
1 May 1999
Catelas I Petit A Marchand R Zukor DJ Yahia L Huk OL

Although the response of macrophages to polyethylene debris has been widely studied, it has never been compared with the cellular response to ceramic debris. Our aim was to investigate the cytotoxicity of ceramic particles (Al. 2. O. 3. and ZrO. 2. ) and to analyse their ability to stimulate the release of inflammatory mediators compared with that of high-density polyethylene particles (HDP). We analysed the effects of particle size, concentration and composition using an in vitro model. The J774 mouse macrophage cell line was exposed to commercial particles in the phagocytosable range (up to 4.5 μm). Al. 2. O. 3. was compared with ZrO. 2. at 0.6 μm and with HDP at 4.5 μm. Cytotoxicity tests were performed using flow cytometry and macrophage cytokine release was measured by ELISA. Cell mortality increased with the size and concentration of Al. 2. O. 3. particles. When comparing Al. 2. O. 3. and ZrO. 2. at 0.6 μm, we did not detect any significant difference at the concentrations analysed (up to 2500 particles per macrophage), and mortality remained very low (less than 10%). Release of TNF-α also increased with the size and concentration of Al. 2. O. 3. particles, reaching 195% of control (165 pg/ml v 84 pg/ml) at 2.4 μm and 350 particles per cell (p < 0.05). Release of TNF-α was higher with HDP than with Al. 2. O. 3. particles at 4.5 μm. However, we did not detect any significant difference in the release of TNF-α between Al. 2. O. 3. and ZrO. 2. at 0.6 μm (p > 0.05). We saw no evidence of release of interleukin-1α or interleukin-1ß after exposure to ceramic or HDP particles


The Journal of Bone & Joint Surgery British Volume
Vol. 94-B, Issue 9 | Pages 1221 - 1227
1 Sep 2012
Kim Y Park J Kim J

Despite many claims of good wear properties following total knee replacement (TKR) with an oxidised zirconium (OxZr) femoral component, there are conflicting clinical results. We hypothesised that there would be no difference in either the mid-term clinical and radiological outcomes or the characteristics of the polyethylene wear particles (weight, size and shape) in patients using an OxZr or cobalt-chrome (CoCr) femoral component. In all 331 patients underwent bilateral TKR, receiving an OxZr femoral component in one knee and a CoCr femoral component in the other. The mean follow-up was 7.5 years (6 to 8). Following aspiration, polyethylene wear particles were analysed using thermogravimetric methods and scanning electron microscopy. At the most recent follow-up, the mean Knee Society score, Western Ontario and McMaster Universities Osteoarthritis Index score, range of movement and satisfaction score were not significantly different in the two groups. The mean weight, size, aspect ratio and roundness of the aspirated wear particles were similar for each femoral component. Survivorship of the femoral, tibial and patellar components was 100% in both groups. In the absence of evidence of an advantage in the medium term we cannot justify the additional expense of an OxZr femoral component.


Bone & Joint Research
Vol. 9, Issue 10 | Pages 667 - 674
1 Oct 2020
Antich-Rosselló M Forteza-Genestra MA Calvo J Gayà A Monjo M Ramis JM

Aims

Platelet concentrates, like platelet-rich plasma (PRP) and platelet lysate (PL), are widely used in regenerative medicine, especially in bone regeneration. However, the lack of standard procedures and controls leads to high variability in the obtained results, limiting their regular clinical use. Here, we propose the use of platelet-derived extracellular vesicles (EVs) as an off-the-shelf alternative for PRP and PL for bone regeneration. In this article, we evaluate the effect of PL-derived EVs on the biocompatibility and differentiation of mesenchymal stromal cells (MSCs).

Methods

EVs were obtained first by ultracentrifugation (UC) and then by size exclusion chromatography (SEC) from non-activated PL. EVs were characterized by transmission electron microscopy, nanoparticle tracking analysis, and the expression of CD9 and CD63 markers by western blot. The effect of the obtained EVs on osteoinduction was evaluated in vitro on human umbilical cord MSCs by messenger RNA (mRNA) expression analysis of bone markers, alkaline phosphatase activity (ALP), and calcium (Ca2+) content.


The Journal of Bone & Joint Surgery British Volume
Vol. 55-B, Issue 4 | Pages 759 - 773
1 Nov 1973
Swanson SAV Freeman MAR Heath JC

1. Currently available total replacement hip and knee prostheses were tested in a machine enabling flexion-extension movements to be applied whilst the prostheses were surrounded with Ringer's solution or other liquid and loaded within the physiological range. 2. Prostheses of which both components were made in cobalt-chromium-molybdenum alloy produced visible quantities of alloy particles, whose sizes ranged down to about 0·1 microns, and cobalt and molybdenum ions in solution. 3. No metallic or plastic particles were detected during tests on a hip prosthesis made of stainless steel and high density polyethylene. 4. The frictional moments in cobalt-chromium-molybdenum hip prostheses were higher than in stainless steel-polyethylene hip prostheses, by a factor of at least 2 to 1. 5. It is accepted that the conditions of these tests were probably more severe than in life, but the difference is held to be one of degree and not one of kind. 6. The particulate alloy debris, when injected in massive doses into the muscles of rats, gave an incidence of malignant tumours which was comparable to that already established for pure cobalt powder, whereas particles of several other metals, tested in the same way, gave no tumours. 7. It is argued that the particles which are known to be produced in at least some patients using cobalt-chromium-molybdenum total replacement joint prostheses constitute a risk of tumour formation which is certainly small, possibly negligible, but not accurately calculable at present. 8. The results of these tests, particularly the differences in frictional moment and in the production of particulate debris, suggest a preference for high density polyethylene as one component of a total joint replacement prosthesis


The Bone & Joint Journal
Vol. 101-B, Issue 8 | Pages 970 - 977
1 Aug 2019
Kleiss S Jandl NM Novo de Oliveira A Rüther W Niemeier A

Aims

The aim of this study was to evaluate the diagnostic accuracy of the synovial alpha-defensin enzyme-linked immunosorbent assay (ELISA) for the diagnosis of prosthetic joint infection (PJI) in the work-up prior to revision of total hip (THA) and knee arthroplasty (TKA).

Patients and Methods

Inclusion criteria for this prospective cohort study were acute or chronic symptoms of the index joint without specific exclusion criteria. Synovial fluid aspirates of 202 patients were analyzed and semiquantitative laboratory alpha-defensin ELISA was performed. Final diagnosis of PJI was established by examination of samples obtained during revision surgery.


Bone & Joint Research
Vol. 7, Issue 6 | Pages 388 - 396
1 Jun 2018
Langton DJ Sidaginamale RP Joyce TJ Bowsher JG Holland JP Deehan D Nargol AVF Natu S

Objectives

We have encountered patients who developed large joint fluid collections with massive elevations in chromium (Cr) and cobalt (Co) concentrations following metal-on-metal (MoM) hip arthroplasties. In some cases, retrieval analysis determined that these ion concentrations could not be explained simply by the wear rates of the components. We hypothesized that these effects may be associated with aseptic lymphocyte-dominated vasculitis-associated lesion (ALVAL).

Patients and Methods

We examined the influence of the ALVAL grade on synovial fluid Co and Cr concentrations following adjustment for patient and device variables, including volumetric wear rates. Initially restricting the analysis to include only patients with one MoM hip resurfacing device, we performed multiple regression analyses of prospectively collected data. We then repeated the same statistical approach using results from a larger cohort with different MoM designs, including total hip arthroplasties.


Bone & Joint Research
Vol. 8, Issue 2 | Pages 65 - 72
1 Feb 2019
Cowie RM Aiken SS Cooper JJ Jennings LM

Objectives

Bone void fillers are increasingly being used for dead space management in arthroplasty revision surgery. The aim of this study was to investigate the influence of calcium sulphate bone void filler (CS-BVF) on the damage and wear of total knee arthroplasty using experimental wear simulation.

Methods

A total of 18 fixed-bearing U2 total knee arthroplasty system implants (United Orthopedic Corp., Hsinchu, Taiwan) were used. Implants challenged with CS-BVF were compared with new implants (negative controls) and those intentionally scratched with a diamond stylus (positive controls) representative of severe surface damage (n = 6 for each experimental group). Three million cycles (MC) of experimental simulation were carried out to simulate a walking gait cycle. Wear of the ultra-high-molecular-weight polyethylene (UHMWPE) tibial inserts was measured gravimetrically, and damage to articulating surfaces was assessed using profilometry.