Aims

Non-coding microRNA (miRNA) in extracellular vesicles (EVs) derived from mesenchymal stem cells (MSCs) may promote neuronal repair after spinal cord injury (SCI). In this paper we report on the effects of MSC-EV-microRNA-381 (miR-381) in a rodent model of SCI.

Aims

Periprosthetic joint infections (PJIs) are among the most devastating complications after joint arthroplasty. There is limited evidence on the efficacy of different antiseptic solutions on reducing biofilm burden. The purpose of the present study was to test the efficacy of different antiseptic solutions against clinically relevant microorganisms in biofilm.

Aims

The primary aim of this study was to compare the postoperative systemic inflammatory response in conventional jig-based total knee arthroplasty (conventional TKA) versus robotic-arm assisted total knee arthroplasty (robotic TKA). Secondary aims were to compare the macroscopic soft tissue injury, femoral and tibial bone trauma, localized thermal response, and the accuracy of component positioning between the two treatment groups.

We examined the cellular responses to various particles injected into the knees and the intramedullary femoral cavities of rats in the presence of polymethyl-methacrylate (PMMA) plugs. The intra-articular particles were mainly ingested by synovial fibroblasts. Increased numbers of macrophages were not detected and there was only a slight increase in synovial thickness. Cellular responses in the intramedullary space were similarly mild and bone resorption around the PMMA plug did not occur. Bone formation was inhibited only by polyethylene particles. In contrast to current views, our study shows that wear particles per se do not initiate bone resorption

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.

Aims

Bone metastasis ultimately occurs due to a complex multistep process, during which the interactions between cancer cells and bone microenvironment play important roles. Prior to colonization of the bone, cancer cells must succeed through a series of steps that will allow them to gain migratory and invasive properties; epithelial-to-mesenchymal transition (EMT) is known to be integral here. The aim of this study was to determine the effects of G protein subunit alpha Q (GNAQ) on the mechanisms underlying bone metastasis through EMT pathway.

Tissues from five patients who underwent revision operations for failed total hip replacements were found to contain large quantities of particulate titanium. In four cases this metal must have come from titanium alloy screws used to fix the acetabular component; in the fifth case it may also have originated from a titanium alloy femoral head. Monoclonal antibody labelling showed abundant macrophages and T-lymphocytes, in the absence of B-lymphocytes, suggesting sensitisation to titanium. Skin patch testing with dilute solutions of titanium salts gave negative results in all five patients. However, two of them had a positive skin test to a titanium-containing ointment

We have investigated whether the presence of polyethylene (PE) alone is sufficient to cause an aggressive periprosthetic tissue response, or whether certain mechanical interface conditions can allow bone to grow while in the presence of PE. An experimental implant was loaded in the presence and absence of particulate PE under stable and unstable conditions. Bone with a thin, discontinuous fibrous membrane formed in both groups of stable implants, either in the presence or absence of PE. By contrast, a continuous fibrous membrane consistently formed in both groups of unstable implants. The membrane consisted of loose fibrous connective tissue when PE was absent, and dense connective tissue with macrophages and a synovial lining when PE was present. In this model, if the interface was stable, the presence of PE was not sufficient to prevent the formation of bone or to produce a phagocytic tissue response. Only when the interface was unstable did a fibrous membrane form, and only then in the presence of PE

1. Rusty staining of the synovial membrane is the gross manifestation of loading of phagocytic synovial-lining cells and of macrophages in the stratum synoviale with haemosiderin. 2. Absorption of blood effused into the joint cavities is the commonest cause of such synovial pigmentation. 3. Obvious discolouration of the synovial tissues usually follows only after repeated haemarthroses, in such conditions as haemophilia, synovial tumour and in some cases of chronic rheumatoid arthritis. 4. An identical naked-eye appearance is seen in multiple joints of patients with generalised haemochromatosis. 5. In haemochromatosis the iron-containing pigment tends to be confined to the surface layer of cells of the synovial membrane. 6. The presence of haemosiderin in synovial cells, per se, leads to no disability of the joint and is unaccompanied either by inflammatory reaction or fibrosis. Arthritis in a patient with haemochromatosis is fortuitous

This is part of a larger study designed to investigate the action of particulate metals of orthopaedic interest on tissues. Damaging effects were determined by cytological examination and the assay of two enzymes. Lactic dehydrogenase (LDH) if released into the supernatant indicates a damaged cell membrane; decreased intracellular levels of glucose-6-phosphate dehydrogenase (G6PD) indicates a lowered phagocytic capacity of the cells. Soluble and wear products around implanted prostheses could facilitate late infections by impairing local reactions to bacteria. Particulate cobalt, nickel and cobalt-chromium alloy were found to damage the cells and to cause LDH release. G6PD was found to have a lower activity in the cells exposed to these materials. In contrast, titanium, chromium and molybdenum were well tolerated by macrophages and had no effect on the distribution and activity of either enzyme. The solubility of these metals in the culture medium was also measured

Of 935 consecutive patients referred with shoulder pain, 50 fitted the criteria for primary frozen shoulder. Twelve patients who failed to improve after conservative treatment and manipulation had excision of the coracohumeral ligament and the rotator interval of the capsule. The specimens were examined histologically, using special stains for collagen. Immunocytochemistry was performed with monoclonal antibodies against leucocyte common antigen (LCA, CD45) and a macrophage/synovial antigen (PGMI, CD68) to assess the inflammatory component, and vimentin and smooth-muscle actin to evaluate fibroblasts and myofibroblasts. Our histological and immunocytochemical findings show that the pathological process is active fibroblastic proliferation, accompanied by some transformation to a smooth muscle phenotype (myofibroblasts). The fibroblasts lay down collagen which appears as a thick nodular band or fleshy mass. These appearances are very similar to those in Dupuytren's disease of the hand, with no inflammation and no synovial involvement. The contracture acts as a check-rein against external rotation, causing loss of both active and passive movement

We report the clinical and tribological performance of 67 ceramic acetabular prostheses implanted between 1976 and 1979 without bone cement. They articulated with ceramic femoral heads mounted on mental femoral stems. After a mean elapsed period of 144 months, 59 sockets were radiographically stable but two showed early signs and six showed late signs of loosening. Four of the loose sockets have been revised. Histological analysis of the retrieved tissue showed a fibrous membrane around all the implants, with fibrocartilage in some. There was no bone ingrowth, and the fibrous membrane was up to 6 mm thick and infiltrated with lymphocytes, plasma cells, and macrophages. Intra- and extracellular birefringent wear particles were seen. Tribological analysis showed total wear rates in two retrieved alumina-on-alumina joints of 2.6 microns per year in a stable implant and 68 microns in a loose implant. Survival analysis showed a revision rate of 12.4% at 136 months

We reviewed a consecutive series of 241 uncemented, porous-coated anatomic (PCA) hip replacements at an average follow-up of five years (2 to 9). Of these, 32 had failed (13%), 26 at the acetabular component (11%) and six at the femoral component (2%). Acetabular failure was associated with local osteolysis and excessive polyethylene wear in 20 cases: in these histological examination showed giant macrophages incorporating numerous particles of high-density polyethylene. The femoral failures were related to a poor intramedullary fit with subsequent subsidence. Using the recommendation for revision as the end point, the cumulative survival rate for prostheses was 91% at six years (95% CI +/- 6%), 73% (+/- 11%) at seven years, and 57% (+/- 20%) at eight years. The result of uncemented PCA hip replacement is satisfactory up to six years, but then increasing failure of the acetabular component appears to be due to polyethylene wear, leading to osteolysis, loosening and component migration. At first, failure is often asymptomatic; routine follow-up of uncemented hip replacement is essential, especially after five years

Coating titanium alloy implants with titanium nitride (TiN) by the method of Powder Immersion Reaction Assisted Coating (PIRAC) produces a stable layer on their surface. We have examined the ability of the new TiN coating to undergo osseointegration. We implanted TiN-coated and uncoated Ti6Al4V alloy pins into the femora of six-month-old female Wistar rats. SEM after two months showed a bone collar around both TiN-coated and uncoated implants. Morphometrical analysis revealed no significant differences between the percentage of the implant-bone contact and the area and volume of the bone around TiN-coated compared with uncoated implants. Electron-probe microanalysis indicated the presence of calcium and phosphorus at the implant-bone interface. Mineralisation around the implants was also confirmed by labelling with oxytetracycline. Strong activity of alkaline phosphatase and weak activity of tartrate-resistant acid phosphatase were shown histochemically. Very few macrophages were detected by the non-specific esterase reaction at the site of implantation. Our findings indicate good biocompatibility and bone-bonding properties of the new PIRAC TiN coatings which are comparable to those of uncoated Ti6Al4V alloy implants

We analysed synovial fluid from 88 hips, 38 with osteoarthritis and 12 with well-functioning and 38 with loose hip prostheses. The levels of TNF-α, IL-1ß (71 hips) and IL-6 (45 hips) were measured using the ELISA technique. Joints with well-functioning or loose prostheses had significantly increased levels of TNF-α compared with those with osteoarthritis. Hips with aseptic loosening also had higher levels of IL-1ß but not of IL-6 compared with those without an implant. The levels of TNF-α and IL-1ß did not differ between hips with stable and loose prostheses. Higher levels of TNF-α were found in hips with bone resorption of type II and type III (Gustilo-Pasternak) compared with those with type-I loosening. The level of cytokines in joint fluid was not influenced by the time in situ of the implants or the age, gender or area of the osteolysis as measured on conventional radiographs. Our findings support the theory that macrophages in the joint capsule increase the production of TNF-α at an early phase probably because of particle load and in the absence of clinical loosening. Since TNF-α has an important role in the osteolytic process, the interfaces should be protected from penetration of joint fluid

Particulate wear debris can induce the release of bone-resorbing cytokines from cultured macrophages and fibroblasts in vitro, and these mediators are believed to be the cause of the periprosthetic bone resorption which leads to aseptic loosening in vivo. Much less is known about the effects of particulate debris on the growth and metabolism of osteoblastic cells. We exposed two human osteoblast-like cell lines (SaOS-2 and MG-63) to particulate cobalt, chromium and cobalt-chromium alloy at concentrations of 0, 0.01, 0.1 and 1.0 mg/ml. Cobalt was toxic to both cell lines and inhibited the production of type-I collagen, osteocalcin and alkaline phosphatase. Chromium and cobalt-chromium were well tolerated by both cell lines, producing no cytotoxicity and no inhibition of type-I collagen synthesis. At the highest concentration tested (1.0 mg/ml), however, chromium inhibited alkaline phosphatase activity, and both chromium and cobalt-chromium alloy inhibited osteocalcin expression. Our results clearly show that particulate metal debris can modulate the growth and metabolism of osteoblastic cells in vitro. Reduced osteoblastic activity at the bone-implant interface may be an important mechanism by which particulate wear debris influences the pathogenesis of aseptic loosening in vivo

Aims

Prosthetic joint infection (PJI) remains a major clinical challenge. Neutrophil CD64 index, Fc-gamma receptor 1 (FcγR1), plays an important role in mediating inflammation of bacterial infections and therefore could be a valuable biomarker for PJI. The aim of this study is to compare the neutrophil CD64 index in synovial and blood diagnostic ability with the standard clinical tests for discrimination PJI and aseptic implant failure.

Aims

To characterize the intracellular penetration of osteoblasts and osteoclasts by methicillin-resistant Staphylococcus aureus (MRSA) and the antibiotic and detergent susceptibility of MRSA in bone.

Mononuclear osteoclast precursors are present in the wear-particle-associated macrophage infiltrate found in the membrane surrounding loose implants. These cells are capable of differentiating into osteoclastic bone-resorbing cells when co-cultured with the rat osteoblast-like cell line, UMR 106, in the presence of 1,25(OH). 2. vitamin D. 3. In order to develop an in vitro model of osteoclast differentiation which more closely parallels the cellular microenvironment at the bone-implant interface in situ, we determined whether osteoblast-like human bone-derived cells were capable of supporting the differentiation of osteoclasts from arthroplasty-derived cells and analysed the humoral conditions required for this to occur. Long-term co-culture of arthroplasty-derived cells and human trabecular-bone-derived cells (HBDCs) resulted in the formation of numerous tartrate-resistant-acid-phosphatase (TRAP) and vitronectin-receptor (VNR)-positive multinucleated cells capable of extensive resorption of lacunar bone. The addition of 1,25(OH). 2. vitamin D. 3. was not required for the formation of osteoclasts and bone resorption. During the formation there was release of substantial levels of M-CSF and PGE. 2. Exogenous PGE. 2. (10. −8. to 10. −6. M) was found to stimulate strongly the resorption of osteoclastic bone. Our study has shown that HBDCs are capable of supporting the formation of osteoclasts from mononuclear phagocyte precursors present in the periprosthetic tissues surrounding a loose implant. The release of M-CSF and PGE. 2. by activated cells at the bone-implant interface may be important for the formation of osteoclasts at sites of pathological bone resorption associated with aseptic loosening

1 . Implants of heterogenous cartilage are known to excite a foreign body reaction in host tissues. In these experiments the way such implants hinder the spread of ossification across a fracture gap was studied. A segment of bone and periosteum was excised from both fibulae in twelve young grivet monkeys, and epiphysial cartilage from a four-day- old rat was implanted in the gap on the left side. The repair processes were investigated at intervals up to twenty-eight weeks. 2. On both sides the gaps were filled by fibrous tissue growing in from the adjacent muscle, and four weeks elapsed before callus started to form. Thereafter ossification across the gap was active on the right side, with bony union in seven or eight weeks. 3. On the left side the implant was slowly resorbed by macrophages and giant cells. Ossification made little headway in the gap after the seventh week. Remains of the implant were found up to the end of the period covered by the experiment. The ends of the fragments were united by fibrous tissue. 4. The fifth to the eighth week seemed to be a critical period, during which the implant and its surrounding inflammatory cells hindered chondrification and ossification and prevented fusion of the masses of callus at the ends of the fragments. 5. It is concluded that anything that impedes callus formation across the fracture line during this critical period may lead to non-union