The alkaline phosphatase activity of pre-osseous tibial cartilage of rachitic bone stored in the deep freeze for two weeks at -25 degrees centigrade was only slightly less than that of fresh controls from the same animals. The deep frozen pre-osseous tissue did not calcify in in vitro calcifying media containing either inorganic phosphorus or organic phosphate ester. The fresh controls calcified equally well in both media. In addition, after deep-freeze storage the tissue hydrolysed the organic phosphate to the same degree as did the fresh tissue. Bones heated at 65 degrees centigrade will calcify in vitro after calcium chloride treatment despite the destruction of phosphatase activity. It appears unlikely that a relationship exists between alkaline phosphatase and the minimal system required for calcification of pre-osseous cartilage in vitro. These findings do not exclude the possibility that alkaline phosphatase plays some critical role in vivo

We have studied the effects of bupivacaine on human and bovine articular chondrocytes in vitro. Time-lapse confocal microscopy of human articular chondrocytes showed > 95% cellular death after exposure to 0.5% bupivacaine for 30 minutes. Human and bovine chondrocytes exposed to 0.25% bupivacaine had a time-dependent reduction in viability, with longer exposure times resulting in higher cytotoxicity. Cellular death continued even after removal of 0.25% bupivacaine. After exposure to 0.25% bupivacaine for 15 minutes, flow cytometry showed bovine chondrocyte viability to be 41% of saline control after seven days. After exposure to 0.125% bupivacaine for up to 60 minutes, the viability of both bovine and human chondrocytes was similar to that of control groups. These data show that prolonged exposure 0.5% and 0.25% bupivacaine solutions are potentially chondrotoxic

1. The use of a protein-free synthetic medium has provided a new technical approach to the study of fracture healing in vitro. 2. The tibiae of fourteen-day embryonic chicks were cut in half in the middle of the shaft, the fragments were placed in apposition and the explants grown in vitro for up to sixteen days. The process of bone repair was studied by means of histology and biochemical estimations. 3. The rate of growth in length of fractured bones was greater in an atmosphere containing 50 per cent of oxygen than in one with 20 per cent oxygen, thus emphasising the importance of an adequate oxygen supply for the regeneration of osteogenic cells. 4. The effect of varying the concentration of glucose in the medium was investigated. Two milligrams of glucose per millilitre was the most favourable for healing; higher levels caused fibroblastic changes in the cartilage cells and inhibited the proliferation of osteogenic cells at the fracture site. 5. Histological examination showed that many of the phenomena that occur in the repair of fractures in vivo can be reproduced in vitro in synthetic medium. Similar results were obtained whether the fracture was made in whole bones or in isolated shafts from which the cartilaginous ends had been removed; the latter are more favourable for biochemical study

Ischaemia kills osteocytes, but opinions differ as to how long they can survive. These differences are due to the varying methods of inducing ischaemia, and to the different criteria for diagnosing cell death. Using rabbit bone and a technique of in vitro ischaemia at 37 degrees C, we have shown by electron microscopy that, after up to two hours, the changes which occur are probably reversible; after four hours, the cells were irreversibly damaged. This difference could not be detected by light microscopy. After 24 hours of ischaemia, most lacunae were empty or contained only osteocyte debris. We conclude that osteocytes suffer irreversible damage after in vitro ischaemia of about two hours, which is much the same response as that of most other mammalian cells

Our aim was to determine whether in vitro studies would detect differences in the cellular response to wear particles of two titanium alloys commonly used in the manufacture of joint replacement prostheses. Particles were of the order of 1 μm in diameter representative of those found adjacent to failed prostheses. Exposure of human monocytes to titanium 6-aluminium 4- vanadium (TiAlV) at concentrations of 4 x 10. 7. particles/ml produced a mean prostaglandin E. 2. release of 2627.6 pM; this was significantly higher than the 317.4 pM induced by titanium 6-aluminium 7-niobium alloy (TiAlNb) particles (p = 0.006). Commercially-pure titanium particles induced a release of 347.8 pM. In addition, TiAlV stimulated significantly more release of the other cell mediators, interleukin-1, tumour necrosis factor and interleukin-6. At lower concentrations of particles there was less mediator release and less obvious differences between materials. None of the materials caused significant toxicity. The levels of inflammatory mediators released by phagocytic cells in response to wear particles may influence the amount of periprosthetic bone loss. Our findings have shown that in vitro studies can detect differences in cellular response induced by particles of similar titanium alloys in common clinical use, although in vivo studies have shown little difference. While in vitro studies should not be used as the only form of assessment, they must be considered when assessing the relative biocompatibility of different implant materials

Biofilm-associated infections in wounds or on implants are difficult to treat. Eradication of the bacteria is nearly always impossible, despite the use of specific antibiotics. The bactericidal effects of high-energy extracorporeal shock waves on Staphylococcus aureus have been reported, but the effect of low-energy shock waves on staphylococci and staphylococcal biofilms has not been investigated. In this study, biofilms grown on stainless steel washers were examined by electron microscopy. We tested ten experimental groups with Staph. aureus-coated washers and eight groups with Staph. epidermidis. The biofilm-cultured washers were exposed to low-energy shock waves at 0.16 mJ/mm. 2. for 500 impulses. The washers were then treated with cefuroxime, rifampicin and fosfomycin, both alone and in combination. All tests were carried out in triplicate. Viable cells were counted to determine the bactericidal effect. The control groups of Staph. aureus and Staph. epidermidis revealed a cell count of 6 × 10. 8. colony-forming units/ml. Complete eradication was achieved using the combination of antibiotic therapy (single antibiotic in Staph. aureus, a combination in Staph. epidermidis) and shock wave application (p < 0.01). We conclude that shock waves combined with antibiotics could be tested in an in vitro model of infection

Hydroxyapatite-coated standard anatomical and customised femoral stems are designed to transmit load to the metaphyseal part of the proximal femur in order to avoid stress shielding and to reduce resorption of bone. In a randomised in vitro study, we compared the changes in the pattern of cortical strain after the insertion of hydroxyapatite-coated standard anatomical and customised stems in 12 pairs of human cadaver femora. A hip simulator reproduced the physiological loads on the proximal femur in single-leg stance and stair-climbing. The cortical strains were measured before and after the insertion of the stems. Significantly higher strain shielding was seen in Gruen zones 7, 6, 5, 3 and 2 after the insertion of the anatomical stem compared with the customised stem. For the anatomical stem, the hoop strains on the femur also indicated that the load was transferred to the cortical bone at the lower metaphyseal or upper diaphyseal part of the proximal femur. The customised stem induced a strain pattern more similar to that of the intact femur than the standard, anatomical stem

We have investigated whether cells derived from haemarthrosis caused by injury to the anterior cruciate ligament could differentiate into the osteoblast lineage in vitro. Haemarthroses associated with anterior cruciate ligament injuries were aspirated and cultured. After treatment with β-glycerophosphate, ascorbic acid and dexamethasone or 1,25 (OH). 2. D. 3. , a significant increase in the activity of alkaline phosphatase was observed. Matrix mineralisation was demonstrated after 28 days and mRNA levels in osteoblast-related genes were enhanced. Our results suggest that the haemarthrosis induced by injury to the anterior cruciate ligament contains osteoprogenitor cells and is a potential alternative source for cell-based treatment in such injury

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

The haematoma occurring at the site of a fracture is known to play an important role in bone healing. We have recently shown the presence of progenitor cells in human fracture haematoma and demonstrated that they have the capacity for multilineage mesenchymal differentiation. There have been many studies which have shown that low-intensity pulsed ultrasound (LIPUS) stimulates the differentiation of a variety of cells, but none has investigated the effects of LIPUS on cells derived from human fracture tissue including human fracture haematoma-derived progenitor cells (HCs). In this in vitro study, we investigated the effects of LIPUS on the osteogenic activity of HCs. Alkaline phosphatase activity, osteocalcin secretion, the expression of osteoblast-related genes and the mineralisation of HCs were shown to be significantly higher when LIPUS had been applied but without a change in the proliferation of the HCs. These findings provide evidence in favour of the use of LIPUS in the treatment of fractures

The diffusion of Fucidin, gentamicin, and clindamycin from acrylic cement was tested in an in vitro system. The activity of Fucidin was very short-lived and only against gram-positive organisms; gentamicin inhibited gram-positive and gram-negative organisms for twenty-two and eleven days respectively; clindamycin had significant action only against gram-positive organisms and retained some activity for fifty-six days. We suggest that the destruction of organisms in the tissues is more likely to be achieved by topical and intravenous administration of antibiotics during the operation than by incorporation of antibiotic in the cement

Aims

This study aimed to determine if macrophages can attach and directly affect the oxide layers of 316L stainless steel, titanium alloy (Ti6Al4V), and cobalt-chromium-molybdenum alloy (CoCrMo) by releasing components of these alloys.

We isolated multilineage mesenchymal progenitor cells from haematomas collected from fracture sites. After the haematoma was manually removed from the fracture site it was cut into strips and cultured. Homogenous fibroblastic adherent cells were obtained. Flow cytometry revealed that the adherent cells were consistently positive for mesenchymal stem-cell-related markers CD29, CD44, CD105 and CD166, and were negative for the haemopoietic markers CD14, CD34, CD45 and CD133 similar to bone-marrow-derived mesenchymal stem cells. In the presence of lineage-specific induction factors the adherent cells could differentiate in vitro into osteogenic, chondrogenic and adipogenic cells. Our results indicate that haematomas found at a fracture site contain multilineage mesenchymal progenitor cells and play an important role in bone healing. Our findings imply that to enhance healing the haematoma should not be removed from the fracture site during osteosynthesis

In vitro studies on isolated bone cells were undertaken to investigate the presence of transplantation (histocompatibility) antigens. Bone cells were cultured with allogeneic lymphocytes and exposed to cytotoxic sera containing antibodies against transplantation antigens, to determine their antigenic profile. Preliminary results suggest that bone cells may not express lymphocyte stimulating antigens in an active form, at least after the isolation procedure performed. On the other hand, bone cells were killed by cytotoxic antibodies in a specific way, providing evidence for the presence of serologically defined (SD) transplantation antigens on the cell surface. Additional studies with absorbed sera suggest "sharing" of histocompatibility antigens between bone cells and lymphocytes. The relevance of the surface antigens of bone cells to clinical fields such as bone allotransplantation, susceptibility to various orthopaedic diseases and skeletal sarcomata is discussed

We have measured the effect of age on the rate of outgrowth of cells from human trabecular bone, using a quantitative dye-binding technique. In cultures supplemented with autologous serum, there were significant negative correlations between the age of the donor and both the proportion of fragments from which outgrowths were seen after 7 days (r = -0.70; p < 0.001) and the total cell number after 14 days (r = -0.78; p < 0.005). The autologous serum supported greater cell proliferation than did fetal calf serum in all subjects regardless of age. Taken with previous observations that the in vitro growth kinetics of passaged human bone cells are independent of age, our results show that the number of proliferative precursor cells on trabecular-bone surfaces is higher in younger subjects. There is a marked decrease in precursor numbers in the second and third decades of life to a level which is maintained into old age

We have investigated whether the particle-stimulated release of inflammatory cytokines from human primary macrophages in vitro was dependent upon the type of bone cement used. Particles of clinically relevant size were produced from Palacos R without radio-opacifier, Palacos R with BaSO. 4. , Palacos R with ZrO. 2. and from CMW3 which contains BaSO. 4. All four preparations produced significantly greater release of tumour necrosis factor alpha, interleukin-6 and interleukin-1 beta than a negative control but there were no significant differences between them. The differences in the ability to stimulate bone resorption and in clinical performance between proprietary bone cements previously recorded are not explained by the release of the cytokines most commonly implicated in osteolysis

We have studied in vitro the effect of a hydroxyapatite (HA) tricalcium phosphate material coated with hepatocyte growth factor (HA-HGF) on cell growth, collagen synthesis and secretion of metalloproteinases (MMPs) by human osteoblasts. Cell proliferation was stimulated when osteoblasts were incubated with untreated HA and was further increased after exposure to HA-HGF. The uptake of [. 3. H]-proline was increased after treatment with HA. When osteoblasts were exposed to HA-HGF, collagen synthesis was increased with respect to HA. The secretion of MMPs in control cells was undetectable, but in HA and HA-HGF cells MMP 2 and MMP 9 were clearly synthesised. Our results suggest that HA can promote osteoblast activity and that HGF can further increase its bioactivity

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

Particulate prosthetic materials are often studied by adding them to monocytic cells in vitro and measuring the release of cytokines as an indicator of their inflammatory potential. Endotoxin is known to be a contaminant of particle preparations and also stimulates the release of cytokines. It is usual to use a proprietary endotoxin test to avoid erroneous results. Four different formulations of cement were found to be free from endotoxin using standard, gelclot tests but stimulated different levels of release of cytokines from macrophages. These differences were explained when a more sensitive, kinetic endotoxin assay showed that release correlated with minor contamination with endotoxin. In a repeat experiment using cement particles with low or undetectable levels of endotoxin by kinetic assay, differences in the ability of the formulations to stimulate the release of cytokines were not seen. Endotoxin is adsorbed on to the surface of particles and it is this combination which stimulates increased release of cytokines. In both the above methods for determination of endotoxin, the water in which the particles had been soaked was examined rather than the particles directly. Further investigations showed that a kinetic assay directly on a particle suspension is the most sensitive method to measure contamination with endotoxin

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

There is increasing evidence that non-steroidal anti-inflammatory drugs (NSAIDs) can adversely affect bone repair. We have, therefore, studied the in vitro effects of NSAIDs, which differentially inhibit cyclooxygenases (COX), the prostaglandin/thromboxane synthesising enzymes, on human osteoblasts. Indomethacin and the new nitric oxide (NO)-donating NSAIDs block the activity of both COX-1 and COX-2. Indomethacin and 5,5-dimethyl-3-(3 fluorophenyl)-4-(4 methylsulphonal) phenyl-2 (5H)-furanone (DFU) reduced osteoblast numbers in a dose-dependant manner and increased collagen synthesis and alkaline phosphatase activity. The reduction in osteoblast numbers was not caused by loss of adhesion and was reversible. Neither NSAID influenced DNA synthesis. There was no difference between the effects of indomethacin and DFU. NO-NSAIDs did not affect cell numbers. These results suggest that care should be taken when administering NSAIDs to patients with existing skeletal problems and that NO-NSAIDs may be safer

Periprosthetic osteolysis is a major cause of aseptic loosening in artificial joint replacement. It is assumed to occur in conjunction with the activation of macrophages. We have shown in vitro that human osteoblast-like cells, isolated from bone specimens obtained from patients undergoing hip replacement, phagocytose fine particles of titanium alloy (TiAlV). The human osteoblast-like cells were identified immunocytochemically by the presence of bone-specific alkaline phosphatase (BAP). With increasing duration of culture, a variable number of the osteoblastic cells became positive for the macrophage marker CD68, independent of the phagocytosis of particles, with a fine granular cytoplasmic staining which was coexpressed with BAP as revealed by immunodoublestaining. The metal particles were not toxic to the osteoblastic cells since even in culture for up to four weeks massively laden cells were vital and had a characteristic morphology. Cells of the human osteosarcoma cell line (HOS 58) were also able to phagocytose metal particles but had only a low expression of the CD68 antigen. Fluorescence-activated cell scanning confirmed our immunocytochemical results. Additionally, the cells were found to be negative for the major histocompatibility complex-II (MHC-II) which is a marker for macrophages and other antigen-presenting cells. Negative results of histochemical tests for tartrate-resistant acid phosphatase excluded the contamination by osteoclasts or macrophages in culture. Our observations suggest that the osteoblast can either change to a phagocytosing cell or that the phagocytosis is an underestimated property of the osteoblast. The detection of the CD68 antigen is insufficient to prove the monocytic lineage. In order to discriminate between macrophages and osteoblasts additional markers should be used. To our knowledge, this is the first demonstration of cells of an osteoblastic origin which have acquired a mixed phenotype of both osteoblasts and macrophages

The success of long-term transcutaneous implants depends on dermal attachment to prevent downgrowth of the epithelium and infection. Hydroxyapatite (HA) coatings and fibronectin (Fn) have independently been shown to regulate fibroblast activity and improve attachment. In an attempt to enhance this phenomenon we adsorbed Fn onto HA-coated substrates. Our study was designed to test the hypothesis that adsorption of Fn onto HA produces a surface that will increase the attachment of dermal fibroblasts better than HA alone or titanium alloy controls.

Iodinated Fn was used to investigate the durability of the protein coating and a bioassay using human dermal fibroblasts was performed to assess the effects of the coating on cell attachment. Cell attachment data were compared with those for HA alone and titanium alloy controls at one, four and 24 hours. Protein attachment peaked within one hour of incubation and the maximum binding efficiency was achieved with an initial droplet of 1000 ng. We showed that after 24 hours one-fifth of the initial Fn coating remained on the substrates, and this resulted in a significant, three-, four-, and sevenfold increase in dermal fibroblast attachment strength compared to uncoated controls at one, four and 24 hours, respectively.

We attempted to characterise the biological quality and regenerative potential of chondrocytes in osteochondritis dissecans (OCD). Dissected fragments from ten patients with OCD of the knee (mean age 27.8 years (16 to 49)) were harvested at arthroscopy. A sample of cartilage from the intercondylar notch was taken from the same joint and from the notch of ten patients with a traumatic cartilage defect (mean age 31.6 years (19 to 52)). Chondrocytes were extracted and subsequently cultured. Collagen types 1, 2, and 10 mRNA were quantified by polymerase chain reaction. Compared with the notch chondrocytes, cells from the dissecate expressed similar levels of collagen types 1 and 2 mRNA. The level of collagen type 10 message was 50 times lower after cell culture, indicating a loss of hypertrophic cells or genes. The high viability, retained capacity to differentiate and metabolic activity of the extracted cells suggests preservation of the intrinsic repair capability of these dissecates. Molecular analysis indicated a phenotypic modulation of the expanded dissecate chondrocytes towards a normal phenotype. Our findings suggest that cartilage taken from the dissecate can be reasonably used as a cell source for chondrocyte implantation procedures.

Aspiration arthrography using an iodinated contrast medium is a useful tool for the investigation of septic or aseptic loosening of arthroplasties and of septic arthritis. Previously, the contrast media have been thought to cause false negative results in cultures when present in aspirated samples of synovial fluid, probably because free iodine is bactericidal, but reports have been inconclusive.

We examined the influence of the older, high osmolar contrast agents and the low osmolar media used currently on the growth of ten different micro-organisms capable of causing deep infection around a prosthesis. Five media were tested, using a disc diffusion technique and a time-killing curve method in which high and low inocula of micro-organisms were incubated in undiluted media. The only bactericidal effects were found with low inocula of Escherichia coli and Pseudomonas aeruginosa in ioxithalamate, one of the older ionic media.

The low and iso-osmolar iodinated contrast media used currently do not impede culture. Future study must assess other causes of false negative cultures of synovial fluid and new developments in enhancing microbial recovery from aspirated samples.

The Oxford medial unicompartmental knee replacement was designed to reproduce normal mobility and forces in the knee, but its detailed effect on the patellofemoral joint has not been studied previously. We have examined the effect on patellofemoral mechanics of the knee by simultaneously measuring patellofemoral kinematics and forces in 11 cadaver knee specimens in a supine leg-extension rig. Comparison was made between the intact normal knee and sequential unicompartmental and total knee replacement. Following medial mobile-bearing unicompartmental replacement in 11 knees, patellofemoral kinematics and forces did not change significantly from those in the intact knee across any measured parameter. In contrast, following posterior cruciate ligament retaining total knee replacement in eight knees, there were significant changes in patellofemoral movement and forces.

The Oxford device appears to produce near-normal patellofemoral mechanics, which may partly explain the low incidence of complications with the extensor mechanism associated with clinical use.

Aseptic loosening and osteolysis around prosthetic joints are the principal causes of failure and consequent revision. During this process activated macrophages produce cytokines which are thought to promote osteolysis by osteoclasts. Changes in pressure within the space around implants have been proposed as a cause of loosening and osteolysis. We therefore studied the effect of two different regimes of cyclic pressure on the production of interleukin-1β (IL-1β), IL-6 and tumour necrosis factor-α (TNF-α) by cultured human monocyte-derived (M-D) macrophages. There was a wide variation in the expression of cytokines in non-stimulated M-D macrophages from different donors and therefore cells from the same donor were compared under control and pressurised conditions.

Both regimes of cyclic pressure were found to increase expression of IL-6 and TNF-α. Expression of IL-1β was increased by a higher-frequency regime only. Our findings suggest that M-D macrophages are activated by cyclic pressure. Further work will be required to understand the relative roles of frequency, amplitude and duration of applied pressure in the cellular effects of cyclic pressure in this system.

Bone tumours may recur locally even after wide surgical excision and systemic chemotherapy. Local control of growth may be accomplished by the addition of cytostatic drugs such as methotrexate (MTX) to bone cement used to fill the defect after surgery and to stabilise the reconstructive prosthesis. We have studied the elution kinetics of MTX and its solvent N-methyl-pyrrolidone (NMP) from bone cement and their biological activities in five cell lines of osteosarcoma and in osteoblasts, and compared them with the effects of the parent compounds alone and in combination.

Our findings show that MTX is released continuously over months at concentrations highly cytotoxic to osteosarcoma cells and suggest that the impregnated bone cement would be effective in the long term. Proliferating osteoblasts, however, were much less sensitive towards MTX. The dose-response relationship for NMP and experiments with MTX/NMP-mixtures show that the eluted concentrations of solvent are not toxic and do not influence the effects of MTX.

We suggest that bone cement containing MTX dissolved in NMP releases the drug in a suitable and effective way and may be of value in the treatment of bone tumours.

Rat patellae were preincubated with culture medium M199 for one hour and then with either fresh culture medium or Ringer's solution, Ringer lactate, Ringer glucose, normal saline or Betadine for another hour. The rate of proteoglycan synthesis in the articular cartilage was then measured by uptake of 35SO4 for the next 16 hours. Cartilage metabolism was inhibited by all of the solutions even after a recovery time of 16 hours. The inhibition was by 5% for Ringer's solution, 10% for Ringer glucose (p < 0.01), 20% for saline and Ringer lactate (p < 0.001) and 55% for Betadine (p < 0.001). Ringer's solution is therefore the best choice for joint irrigation during arthroscopy or other procedures.

Calvaria from six-day-old infant mice were grown on a grid culture in a chemically defined medium under varying oxygen tensions. Quantitative isotope studies demonstrated a linear association between bone resorption and oxygen tension in the physiological range. This result was supported by histological, histochemical and vital staining experiments. The clinical finding of osteoporosis in areas of hyperaemia could therefore be attributed to a rise in oxygen tension causing increased bone resorption.

High-pressure lavage produces greater visible damage to bone at a macroscopic and microscopic level when compared with low-pressure lavage and can result in delay in the healing of fractures. Osteoblasts and adipocytes are derived from mesenchymal stem cells. Conditions which lead to bone loss often involve a switch from the osteoblast to adipocyte lineage. We have therefore examined the effect of high- and low-pressure irrigation on the differentiation of adipocytes.

Calvaria-derived bone cells were exposed to either low-pressure or high-pressure irrigation with normal saline. After 14 days the cells were fixed and the osteoblasts and adipocytes quantified using Oil Red O to stain cytoplasmic lipid droplets (triglycerides) in the cells. Osteoblasts were quantified using a commercially available alkaline-phosphatase staining assay.

A standard quantitative reverse transcription-polymerase chain reaction (RT-PCR) was performed. Messenger RNA levels for osteocalcin, a marker of osteoblasts, and PPARγ2, a marker of adipocytes, were measured. High-pressure lavage resulted in an increase in adipogenesis of 50% when compared with low-pressure lavage.

Our findings suggest that high-pressure lavage may promote differentiation of mesenchymal stem cells towards the adipoctye lineage. This may have clinical significance in the development of delayed and nonunion after treatment of fractures of long bones.

Using a new, non-invasive method, we measured the patellofemoral force (PFF) in cadaver knees mounted in a rig to simulate weight-bearing. The PFF was measured from 20° to 120° of flexion before and after implanting three designs of knee prosthesis.

Medial unicompartmental arthroplasty with a meniscal-bearing prosthesis and with retention of both cruciate ligaments caused no significant change in the PFF. After arthroplasty with a posterior-cruciate-retaining prosthesis and division of the anterior cruciate ligament, the PFF decreased in extension and increased by 20% in flexion. Implantation of a posterior stabilised prosthesis and division of both cruciate ligaments produced a decrease in the PFF in extension but maintained normal load in flexion.

There was a direct relationship between the PFF and the angle made with the patellar tendon and the long axis of the tibia. The abnormalities of the patellar tendon angle which resulted from implantation of the two total prostheses explain the observed changes in the PFF and show how the mechanics of the patellofemoral joint depend upon the kinematics of the tibiofemoral articulation.

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.

Sterilisation by gamma irradiation in the presence of air causes free radicals generated in polyethylene (PE) to react with oxygen, which could lead to loss of physical properties and reduction in fatigue strength. Tissue retrieved from failed total hip replacements often has large quantities of particulate PE and most particles associated with peri-implant osteolysis are oxidised. Consequently, an understanding of the cellular responses of oxidised PE particles may lead to clarification of the pathogenesis of osteolysis and aseptic loosening.

We have used the agarose system to demonstrate the differential effects of oxidised and non-oxidised PE particles on the release of proinflammatory products such as interleukin-1β (IL-1β), IL-6, and tumour necrosis factor-α (TNF-α) from monocytes/ macrophages (M/M). Oxidised PE particles were shown to stimulate human M/M to phagocytose and to release cytokines. Oxidation may alter the surface chemistry of the particles and enhance the response to specific membrane receptors on macrophages, such as scavenger-type receptors.

We exposed human macrophages isolated from the peripheral blood of healthy donors to metal and bone-cement particles from 0.2 to 10 μm in size.

Zymography showed that macrophages exposed to titanium alloy and polymethylmethacrylate (PMMA) particles released a 92- and 72-kDa gelatinase in a dose- and time-dependent manner. Western immunoblotting confirmed that the 92- and 72-kDa gelatinolytic activities corresponded to matrix metalloproteinase-9 and matrix metalloproteinase-2 (MMP-9, MMP-2), respectively. Western immunoblotting also indicated that titanium alloy and PMMA particles increased the release of MMP-1. Northern blotting showed elevated mRNA signal levels for MMP-1, MMP-2, and MMP-9 after exposure to both types of particle. Collagenolytic activity also increased in the macrophage culture medium in response to both types of particle.

Our findings support the hypothesis that macrophages release MMPs in proportion to the amount of particulate debris within periprosthetic tissues.

1. Methods for culturing cells isolated from slices of arthritic human or normal mammalian cancellous bone are described.

2. The capacity of the cultured cells to take up and hydroxylate labelled proline has been investigated.

3. Sections of the partially decalcified bone and of the isolated cells have been examined by transmission electron microscopy.

4. The possible significance of the results and observations are discussed. We are deeply grateful to Dame Janet Vaughan, who very kindly read this manuscript and made several valuable suggestions and criticisms. We are much obliged to Dr Sylvia Fitton-Jackson for her advice on the techniques of tissue culture and for giving us the composition of her chemically defined medium. Dr Palfrey kindly allowed one of us, M. J. Dickens, to learn transmission electron microscopy in his department at St Thomas's Hospital Medical School under the expert tuition of Mr G. Maxwell. Mr R. Hockhan and Mr M. Hepburn of the University of Surrey Structural Studies Unit helpfully instructed in the operation of the transmission electron microscope. Our special thanks are due to Mr E. P. Morris for his competent and enthusiastic technical assistance.

It is well recognised that meniscal tears situated within the inner, avascular region do not heal. We investigated the potential effect of insulin-like growth factor-I (IGF-I) in promoting regeneration of meniscal tissue in the inner, middle and outer zones of the meniscus. Sheep menisci were harvested and monolayer cell cultures prepared. Various concentrations of IGF-I were used in the presence or absence of 10% fetal calf serum (FCS). We measured the uptake of radioactive thymidine, sulphur, and proline to assess cell proliferation and formation of extracellular matrix (ECM). IGF-I, in the presence or absence of FCS, increased the formation of DNA and ECM in all meniscal zones. However, the response of the cells from the avascular zone was greater than that from the vascular zone. Our findings indicate that fibrochondrocytes cultured from avascular meniscal tissue have the ability to regenerate when exposed to anabolic cytokines such as IGF-I.

Aims. Bacterial infection activates neutrophils to release neutrophil extracellular traps (NETs) in bacterial biofilms of periprosthetic joint infections (PJIs). The aim of this study was to evaluate the increase in NET activation and release (NETosis) and haemostasis markers in the plasma of patients with PJI, to evaluate whether such plasma induces the activation of neutrophils, to ascertain whether increased NETosis is also mediated by reduced DNaseI activity, to explore novel therapeutic interventions for NETosis in PJI in vitro, and to evaluate the potential diagnostic use of these markers. Methods. We prospectively recruited 107 patients in the preoperative period of prosthetic surgery, 71 with a suspicion of PJI and 36 who underwent arthroplasty for non-septic indications as controls, and obtained citrated plasma. PJI was confirmed in 50 patients. We measured NET markers, inflammation markers, DNaseI activity, haemostatic markers, and the thrombin generation test (TGT). We analyzed the ability of plasma from confirmed PJI and controls to induce NETosis and to degrade in vitro-generated NETs, and explored the therapeutic restoration of the impairment to degrade NETs of PJI plasma with recombinant human DNaseI. Finally, we assessed the contribution of these markers to the diagnosis of PJI. Results. Patients with confirmed PJI had significantly increased levels of NET markers (cfDNA (p < 0.001), calprotectin (p < 0.001), and neutrophil elastase (p = 0.022)) and inflammation markers (IL-6; p < 0.001) in plasma. Moreover, the plasma of patients with PJI induced significantly more neutrophil activation than the plasma of the controls (p < 0.001) independently of tumour necrosis factor alpha. Patients with PJI also had a reduced DNaseI activity in plasma (p < 0.001), leading to a significantly impaired degradation of NETs (p < 0.001). This could be therapeutically restored with recombinant human DNaseI to the level in the controls. We developed a model to improve the diagnosis of PJI with cfDNA, calprotectin, and the start tail of TGT as predictors, though cfDNA alone achieved a good prediction and is simpler to measure. Conclusion. We confirmed that patients with PJI have an increased level of NETosis in plasma. Their plasma both induced NET release and had an impaired ability to degrade NETs mediated by a reduced DNaseI activity. This can be therapeutically restored in vitro with the approved Dornase alfa, Pulmozyme, which may allow novel methods of treatment. A combination of NETs and haemostatic biomarkers could improve the diagnosis of PJI, especially those patients in whom this diagnosis is uncertain. Cite this article: Bone Joint J 2024;106-B(9):1021–1030

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. Methods. We conducted an in vitro study examining the efficacy of several antiseptic solutions against clinically relevant microorganisms. We tested antiseptic irrigants against nascent (four-hour) and mature (three-day) single-species biofilm created in vitro using a drip-flow reactor model. Results. With regard to irrigant efficacy against biofilms, Povidone-iodine treatment resulted in greater reductions in nascent MRSA biofilms (logarithmic reduction (LR) = 3.12; p < 0.001) compared to other solutions. Bactisure treatment had the greatest reduction of mature Pseudomonas aeruginosa biofilms (LR = 1.94; p = 0.032) and a larger reduction than Vashe or Irrisept for mature Staphylococcus epidermidis biofilms (LR = 2.12; p = 0.025). Pooled data for all biofilms tested resulted in Bactisure and Povidone-iodine with significantly greater reductions compared to Vashe, Prontosan, and Irrisept solutions (p < 0.001). Conclusion. Treatment failure in PJI is often due to failure to clear the biofilm; antiseptics are often used as an adjunct to biofilm clearance. We tested irrigants against clinically relevant microorganisms in biofilm in vitro and showed significant differences in efficacy among the different solutions. Further clinical outcome data is necessary to determine whether these solutions can impact PJI outcome in vivo. Cite this article: Bone Joint J 2021;103-B(5):908–915

Aims. The survival of humeral hemiarthroplasties in patients with relatively intact glenoid cartilage could theoretically be extended by minimizing the associated postoperative glenoid erosion. Ceramic has gained attention as an alternative to metal as a material for hemiarthroplasties because of its superior tribological properties. The aim of this study was to assess the in vitro wear performance of ceramic and metal humeral hemiarthroplasties on natural glenoids. Methods. Intact right cadaveric shoulders from donors aged between 50 and 65 years were assigned to a ceramic group (n = 8, four male cadavers) and a metal group (n = 9, four male cadavers). A dedicated shoulder wear simulator was used to simulate daily activity by replicating the relevant joint motion and loading profiles. During testing, the joint was kept lubricated with diluted calf serum at room temperature. Each test of wear was performed for 500,000 cycles at 1.2 Hz. At intervals of 125,000 cycles, micro-CT scans of each glenoid were taken to characterize and quantify glenoid wear by calculating the change in the thickness of its articular cartilage. Results. At the completion of the wear test, the total thickness of the cartilage had significantly decreased in both the ceramic and metal groups, by 27% (p = 0.019) and 29% (p = 0.008), respectively. However, the differences between the two were not significant (p = 0.606) and the patterns of wear in the specimens were unpredictable. No significant correlation was found between cartilage wear and various factors, including age, sex, the size of the humeral head, joint mismatch, the thickness of the native cartilage, and the surface roughness (all p > 0.05). Conclusion. Although ceramic has better tribological properties than metal, we did not find evidence that its use in hemiarthroplasty of the shoulder in patients with healthy cartilage is a better alternative than conventional metal humeral heads. Cite this article: Bone Joint J 2024;106-B(11):1273–1283

Aims. Current treatments of prosthetic joint infection (PJI) are minimally effective against Staphylococcus aureus biofilm. A murine PJI model of debridement, antibiotics, and implant retention (DAIR) was used to test the hypothesis that PlySs2, a bacteriophage-derived lysin, can target S. aureus biofilm and address the unique challenges presented in this periprosthetic environment. Methods. The ability of PlySs2 and vancomycin to kill biofilm and colony-forming units (CFUs) on orthopaedic implants were compared using in vitro models. An in vivo murine PJI model of DAIR was used to assess the efficacy of a combination of PlySs2 and vancomycin on periprosthetic bacterial load. Results. PlySs2 treatment reduced 99% more CFUs and 75% more biofilm compared with vancomycin in vitro. A combination of PlySs2 and vancomycin in vivo reduced the number of CFUs on the surface of implants by 92% and in the periprosthetic tissue by 88%. Conclusion. PlySs2 lysin was able to reduce biofilm, target planktonic bacteria, and work synergistically with vancomycin in our in vitro models. A combination of PlySs2 and vancomycin also reduced bacterial load in periprosthetic tissue and on the surface of implants in a murine model of DAIR treatment for established PJI. Cite this article: Bone Joint J 2020;102-B(7 Supple B):3–10

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

Aims. This combined clinical and in vitro study aimed to determine the incidence of liner malseating in modular dual mobility (MDM) constructs in primary total hip arthroplasties (THAs) from a large volume arthroplasty centre, and determine whether malseating increases the potential for fretting and corrosion at the modular metal interface in malseated MDM constructs using a simulated corrosion chamber. Methods. For the clinical arm of the study, observers independently reviewed postoperative radiographs of 551 primary THAs using MDM constructs from a single manufacturer over a three-year period, to identify the incidence of MDM liner-shell malseating. Multivariable logistic regression analysis was performed to identify risk factors including age, sex, body mass index (BMI), cup design, cup size, and the MDM case volume of the surgeon. For the in vitro arm, six pristine MDM implants with cobalt-chrome liners were tested in a simulated corrosion chamber. Three were well-seated and three were malseated with 6° of canting. The liner-shell couples underwent cyclic loading of increasing magnitudes. Fretting current was measured throughout testing and the onset of fretting load was determined by analyzing the increase in average current. Results. The radiological review identified that 32 of 551 MDM liners (5.8%) were malseated. Malseating was noted in all of the three different cup designs. The incidence of malseating was significantly higher in low-volume MDM surgeons than high-volume MDM surgeons (p < 0.001). Pristine well-seated liners showed significantly lower fretting current values at all peak loads greater than 800 N (p < 0.044). Malseated liner-shell couples had lower fretting onset loads at 2,400 N. Conclusion. MDM malseating remains an issue that can occur in at least one in 20 patients at a high-volume arthroplasty centre. The onset of fretting and increased fretting current throughout loading cycles suggests susceptibility to corrosion when this occurs. These results support the hypothesis that malseated liners may be at risk for fretting corrosion. Clinicians should be aware of this phenomenon. Cite this article: Bone Joint J 2020;102-B(7 Supple B):20–26

Aims. The aim of this study was to compare the ability of tantalum, 3D porous titanium, antibiotic-loaded bone cement, and smooth titanium alloy to inhibit staphylococci in an in vitro environment, based on the evaluation of the zone of inhibition (ZOI). The hypothesis was that there would be no significant difference in the inhibition of methicillin-sensitive or methicillin-resistant Staphylococcus aureus (MSSA/MRSA) between the two groups. Methods. A total of 30 beads made of three different materials (tantalum/3D porous titanium and smooth titanium alloy) were bathed for one hour in a solution of 1 g vancomycin in 20 ml of sterile water for injection (bath concentration: 50 mg/mL). Ten 1 cm. 3. cylinders of antibiotic-loaded cement were also created by mixing standard surgical cement with 1 g of vancomycin in standardized sterile moulds. The cylinders were then placed on agar plates inoculated with MSSA and MRSA. The ZOIs were measured each day and the cylinders were transferred onto a new inoculated plate. Results. For MSSA and MRSA, no inhibitory effect was found in the control group, and antibiotic-loaded smooth titanium alloy beads showed a short inhibitory effect until day 2. For MSSA, both tantalum and 3D porous titanium beads showed significantly larger mean ZOIs than cement beads (all p < 0.01) each day until day 7 for tantalum and until day 3 for 3D porous titanium. After six days, antibiotic-loaded cement had significantly larger mean ZOIs than the 3D porous titanium (p = 0.027), but no significant difference was found with tantalum (p = 0.082). For MRSA, both tantalum and 3D porous titanium beads had significantly larger mean ZOIs than antibiotic-loaded cement each day until day 6 for tantalum (all p < 0.01) and until day 3 for 3D porous titanium (all p < 0.04). Antibiotic-loaded cement had significantly larger mean ZOIs than tantalum and 3D porous titanium from day 7 to 9 (all p < 0.042). Conclusion. These results show that porous metal implants can deliver local antibiotics over slightly varying time frames based on in vitro analysis. Cite this article: Bone Joint J 2020;102-B(6 Supple A):158–162

Antibiotic resistance represents a threat to human health. It has been suggested that by 2050, antibiotic-resistant infections could cause ten million deaths each year. In orthopaedics, many patients undergoing surgery suffer from complications resulting from implant-associated infection. In these circumstances secondary surgery is usually required and chronic and/or relapsing disease may ensue. The development of effective treatments for antibiotic-resistant infections is needed. Recent evidence shows that bacteriophage (phages; viruses that infect bacteria) therapy may represent a viable and successful solution. In this review, a brief description of bone and joint infection and the nature of bacteriophages is presented, as well as a summary of our current knowledge on the use of bacteriophages in the treatment of bacterial infections. We present contemporary published in vitro and in vivo data as well as data from clinical trials, as they relate to bone and joint infections. We discuss the potential use of bacteriophage therapy in orthopaedic infections. This area of research is beginning to reveal successful results, but mostly in nonorthopaedic fields. We believe that bacteriophage therapy has potential therapeutic value for implant-associated infections in orthopaedics. Cite this article: Bone Joint J 2021;103-B(2):234–244

Aims. The aim of this study was to develop a single-layer hybrid organic-inorganic sol-gel coating that is capable of a controlled antibiotic release for cementless hydroxyapatite (HA)-coated titanium orthopaedic prostheses. Methods. Coatings containing gentamicin at a concentration of 1.25% weight/volume (wt/vol), similar to that found in commercially available antibiotic-loaded bone cement, were prepared and tested in the laboratory for: kinetics of antibiotic release; activity against planktonic and biofilm bacterial cultures; biocompatibility with cultured mammalian cells; and physical bonding to the material (n = 3 in all tests). The sol-gel coatings and controls were then tested in vivo in a small animal healing model (four materials tested; n = 6 per material), and applied to the surface of commercially pure HA-coated titanium rods. Results. The coating released gentamicin at > 10 × minimum inhibitory concentration (MIC) for sensitive staphylococcal strains within one hour thereby potentially giving effective prophylaxis for arthroplasty surgery, and showed > 99% elution of the antibiotic within the coating after 48 hours. There was total eradication of both planktonic bacteria and established bacterial biofilms of a panel of clinically relevant staphylococci. Mesenchymal stem cells adhered to the coated surfaces and differentiated towards osteoblasts, depositing calcium and expressing the bone marker protein, osteopontin. In the in vivo small animal bone healing model, the antibiotic sol-gel coated titanium (Ti)/HA rod led to osseointegration equivalent to that of the conventional HA-coated surface. Conclusion. In this study we report a new sol-gel technology that can release gentamicin from a bioceramic-coated cementless arthroplasty material. In vitro, local gentamicin levels are in excess of what can be achieved by antibiotic-loaded bone cement. In vivo, bone healing in an animal model is not impaired. This, thus, represents a biomaterial modification that may have the potential to protect at-risk patients from implant-related deep infection. Cite this article: Bone Joint J 2021;103-B(3):522–529

Aims. The aim of this study was to estimate the 90-day risk of revision for periprosthetic femoral fracture associated with design features of cementless femoral stems, and to investigate the effect of a collar on this risk using a biomechanical in vitro model. Materials and Methods. A total of 337 647 primary total hip arthroplasties (THAs) from the United Kingdom National Joint Registry (NJR) were included in a multivariable survival and regression analysis to identify the adjusted hazard of revision for periprosthetic fracture following primary THA using a cementless stem. The effect of a collar in cementless THA on this risk was evaluated in an in vitro model using paired fresh frozen cadaveric femora. Results. The prevalence of early revision for periprosthetic fracture was 0.34% (1180/337 647) and 44.0% (520/1180) occurred within 90 days of surgery. Implant risk factors included: collarless stem, non-grit-blasted finish, and triple-tapered design. In the in vitro model, a medial calcar collar consistently improved the stability and resistance to fracture. Conclusion. Analysis of features of stem design in registry data is a useful method of identifying implant characteristics that affect the risk of early periprosthetic fracture around a cementless femoral stem. A collar on the calcar reduced the risk of an early periprosthetic fracture and this was confirmed by biomechanical testing. This approach may be useful in the analysis of other uncommon modes of failure after THA. Cite this article: Bone Joint J 2019;101-B:779–786

Aims

Delayed postoperative inoculation of orthopaedic implants with persistent wound drainage or bacterial seeding of a haematoma can result in periprosthetic joint infection (PJI). The aim of this in vivo study was to compare the efficacy of vancomycin powder with vancomycin-eluting calcium sulphate beads in preventing PJI due to delayed inoculation.

Aims. The aims of this study were to compare the mean duration of antibiotic release and the mean zone of inhibition between vancomycin-loaded porous tantalum cylinders and antibiotic-loaded bone cement at intervals, and to evaluate potential intrinsic antimicrobial properties of tantalum in an in vitro medium environment against methicillin-sensitive Staphylococcus aureus (MSSA). Materials and Methods. Ten porous tantalum cylinders and ten cylinders of cement were used. The tantalum cylinders were impregnated with vancomycin, which was also added during preparation of the cylinders of cement. The cylinders were then placed on agar plates inoculated with MSSA. The diameter of the inhibition zone was measured each day, and the cylinders were transferred to a new inoculated plate. Inhibition zones were measured with a Vernier caliper and using an automated computed evaluation, and the intra- and interobserver reproducibility were measured. The mean inhibition zones between the two groups were compared with Wilcoxon’s test. Results. MSSA was inhibited for 12 days by the tantalum cylinders and for nine days by the cement cylinders. At day one, the mean zone of inhibition was 28.6 mm for the tantalum and 19.8 mm for the cement group (p < 0.001). At day ten, the mean zone of inhibition was 3.8 mm for the tantalum and 0 mm for the cement group (p < 0.001). The porous tantalum cylinders soaked only with phosphate buffered solution showed no zone of inhibition. Conclusion. Compared with cement, tantalum could release antibiotics for longer. Further studies should assess the advantages of using antibiotic-loaded porous tantalum implants at revision arthroplasty. Cite this article: Bone Joint J 2019;101-B:848–851

Aims

The aim of this retrospective study was to assess the incidence of early periprosthetic femoral fracture (PFF) associated with Charnley-Kerboull (CK) femoral components cemented according to the ‘French paradox’ principles through the Hueter anterior approach (HAA) in patients older than 70 years.

Aims

Several short- and mid-term studies have shown minimal liner wear of highly cross-linked polyethylene (HXLPE) in total hip arthroplasty (THA), but the safety of using thinner HXLPE liners to maximize femoral head size remains uncertain. The objective of this study was to analyze clinical survival and radiological wear rates of patients with HXLPE liners, a 36 mm femoral head, and a small acetabular component with a minimum of ten years’ follow-up.

Aims

Fixation techniques used in the treatment of slipped capital femoral epiphysis (SCFE) that allow continued growth of the femoral neck, rather than inducing epiphyseal fusion in situ, have the advantage of allowing remodelling of the deformity. The aims of this study were threefold: to assess whether the Free-Gliding (FG) SCFE screw prevents further slip; to establish whether, in practice, it enables lengthening and gliding; and to determine whether the age of the patient influences the extent of glide.

Aims

The aim of this study was to compare the migration of the femoral component, five years postoperatively, between patients with a highly cross-linked polyethylene (HXLPE) insert and those with a conventional polyethylene (PE) insert in an uncemented Triathlon fixed insert cruciate-retaining total knee arthroplasty (TKA). Secondary aims included clinical outcomes and patient-reported outcome measures (PROMs). We have previously reported the migration and outcome of the tibial components in these patients.

Aims

Implantation of ultra-purified alginate (UPAL) gel is safe and effective in animal osteochondral defect models. This study aimed to examine the applicability of UPAL gel implantation to acellular therapy in humans with cartilage injury.

Aims

Surgical approaches that claim to be minimally invasive, such as the direct anterior approach (DAA), are reported to have a clinical advantage, but are technically challenging and may create more injury to the soft-tissues during joint exposure. Our aim was to quantify the effect of soft-tissue releases on the joint torque and femoral mobility during joint exposure for hip resurfacing performed via the DAA.

Aims

The primary objective of this study was to compare the five-year tibial component migration and wear between highly crosslinked polyethylene (HXLPE) inserts and conventional polyethylene (PE) inserts of the uncemented Triathlon fixed insert cruciate-retaining total knee arthroplasty (TKA). Secondary objectives included clinical outcomes and patient-reported outcome measures (PROMs).

Aims

The aim of the study was to investigate whether the primary stability of press-fit acetabular components can be improved by altering the impaction procedure.

Aims

As an increasing number of female surgeons are choosing orthopaedics, it is important to recognize the impact of pregnancy within this cohort. The aim of this review was to examine common themes and data surrounding pregnancy, parenthood, and fertility within orthopaedics.

Aims

Refobacin Bone Cement R and Palacos R + G bone cement were introduced to replace the original cement Refobacin Palacos R in 2005. Both cements were assumed to behave in a biomechanically similar fashion to the original cement. The primary aim of this study was to compare the migration of a polished triple-tapered femoral stem fixed with either Refobacin Bone Cement R or Palacos R + G bone cement. Repeated radiostereometric analysis was used to measure migration of the femoral head centre. The secondary aims were evaluation of cement mantle, stem positioning, and patient-reported outcome measures.

Aims

The purpose of this study was to evaluate the mid-term outcomes of autologous matrix-induced chondrogenesis (AMIC) for the treatment of larger cartilage lesions and deformity correction in hips suffering from symptomatic femoroacetabular impingement (FAI).

Aims

Knee osteoarthritis (OA) is characterized by a chronic inflammatory process involving multiple cytokine pathways, leading to articular cartilage degeneration. Intra-articular therapies using pharmaceutical or autologous anti-inflammatory factors offer potential non-surgical treatment options. Autologous protein solution (APS) is one such product that uses the patient’s blood to produce a concentrate of cells and anti-inflammatory cytokines. This study evaluated the effect of a specific APS intra-articular injection (nSTRIDE) on patient-reported outcome measures compared to saline in moderate knee OA.

Aims

This systematic review and meta-analysis aimed to compare the influence of patellar resurfacing following cruciate-retaining (CR) and posterior-stabilized (PS) total knee arthroplasty (TKA) on the incidence of anterior knee pain, knee-specific patient-reported outcome measures, complication rates, and reoperation rates.

Aims

Proximal humeral fractures are the third most common fracture among the elderly. Complications associated with fixation include screw perforation, varus collapse, and avascular necrosis of the humeral head. To address these challenges, various augmentation techniques to increase medial column support have been developed. There are currently no recent studies that definitively establish the superiority of augmented fixation over non-augmented implants in the surgical treatment of proximal humeral fractures. The aim of this systematic review and meta-analysis was to compare the outcomes of patients who underwent locking-plate fixation with cement augmentation or bone-graft augmentation versus those who underwent locking-plate fixation without augmentation for proximal humeral fractures.

Aims

Giant cell tumour of bone (GCTB) is a locally aggressive lesion that is difficult to treat as salvaging the joint can be associated with a high rate of local recurrence (LR). We evaluated the risk factors for tumour relapse after treatment of a GCTB of the limbs.

Aims

To determine whether platelet-rich plasma (PRP) injection improves outcomes two years after acute Achilles tendon rupture.

Platelet-rich plasma is a new inductive therapy which is being increasingly used for the treatment of the complications of bone healing, such as infection and nonunion. The activator for platelet-rich plasma is a mixture of thrombin and calcium chloride which produces a platelet-rich gel. We analysed the antibacterial effect of platelet-rich gel in vitro by using the platelet-rich plasma samples of 20 volunteers. In vitro laboratory susceptibility to platelet-rich gel was determined by the Kirby-Bauer disc-diffusion method. Baseline antimicrobial activity was assessed by measuring the zones of inhibition on agar plates coated with selected bacterial strains. Zones of inhibition produced by platelet-rich gel ranged between 6 mm and 24 mm (mean 9.83 mm) in diameter. Platelet-rich gel inhibited the growth of Staphylococcus aureus and was also active against Escherichia coli. There was no activity against Klebsiella pneumoniae, Enterococcus faecalis, and Pseudomonas aeruginosa. Moreover, platelet-rich gel seemed to induce the in vitro growth of Ps. aeruginosa, suggesting that it may cause an exacerbation of infections with this organism. We believe that a combination of the inductive and antimicrobial properties of platelet-rich gel can improve the treatment of infected delayed healing and nonunion

Aims. Early evidence has emerged suggesting that ceramic-on-ceramic articulations induce a different tissue reaction to ceramic-on-polyethylene and metal-on-metal bearings. Therefore, the aim of this study was to investigate the tissue reaction and cellular response to ceramic total hip arthroplasty (THA) materials in vitro, as well as the tissue reaction in capsular tissue after revision surgery of ceramic-on-ceramic THAs. Patients and Methods. We investigated tissue collected at revision surgery from nine ceramic-on-ceramic articulations. we compared our findings with tissue obtained from five metal-on-metal THA revisions, four ceramic-on-polyethylene THAs, and four primary osteoarthritis synovial membranes. The latter were analyzed to assess the amount of tissue fibrosis that might have been present at the time of implantation to enable evaluation, in relation to implantation time, of any subsequent response in the tissues. Results. There was a significant increase in tissue fibrosis with implantation time for all implant types tested. Interestingly, the tissue fibrosis in ceramic-on-ceramic THAs was significantly increased compared with metal-on-metal and ceramic-on-polyethylene. Additionally, we found ceramic wear particles in the periprosthetic tissue of ceramic implants. Fibroblasts responded with expression of cytokines when cultured on alumina-toughened zirconia (ATZ) and zirconia-toughened alumina (ZTA) ceramic surfaces. This response was more pronounced on ATZ ceramics compared with ZTA ceramics. The same inflammatory response was observed with peripheral blood mononuclear cells (PBMCs) cultured on ZTA and ATZ. Conclusion. Our findings therefore, corroborate the previous findings that ceramic-on-ceramic periprosthetic revision tissue is fibrous and offer an explanation for this observation. We detected a long-term inflammatory response of PBMCs and an inflammatory response of fibroblasts to ATZ and ZTA ceramic. These findings partially explain the fibrotic tissue change in periprosthetic tissue of ceramic-on-ceramic bearings. Cite this article: Bone Joint J 2018;100-B:882–90

Aims

Arthroplasties of the elbow, including total elbow arthroplasty, radial head arthroplasty, distal humeral hemiarthroplasty, and radiocapitellar arthroplasty, are rarely undertaken. This scoping review aims to outline the current research in this area to inform the development of future research.

Aims. The intra-articular administration of tranexamic acid (TXA) has been shown to be effective in reducing blood loss in unicompartmental knee arthroplasty and anterior cruciate reconstruction. The effects on human articular cartilage, however, remains unknown. Our aim, in this study, was to investigate any detrimental effect of TXA on chondrocytes, and to establish if there was a safe dose for its use in clinical practice. The hypothesis was that TXA would cause a dose-dependent damage to human articular cartilage. . Materials and Methods. The cellular morphology, adhesion, metabolic activity, and viability of human chondrocytes when increasing the concentration (0 mg/ml to 40 mg/ml) and length of exposure to TXA (0 to 12 hours) were analyzed in a 2D model. This was then repeated, excluding cellular adhesion, in a 3D model and confirmed in viable samples of articular cartilage. Results. Increasing concentrations above 20 mg/ml resulted in atypical morphology, reduced cellular adhesion and metabolic activity associated with increased chondrocyte death. However, the cell matrix was not affected by the concentration of TXA or the length of exposure, and offered cellular protection for concentrations below 20 mg/ml. Conclusion. These results show that when in vitro chondrocytes are exposed to higher concentrations of TXA, such as that expected following recommended intra-articular administration, cytotoxicity is observed. This effect is dose-dependent, such that a tissue concentration of 10 mg/ml to 20 mg/ml could be expected to be safe. Cite this article: Bone Joint J 2018;100-B:404–12

Hip implant retrieval analysis is the most important source of insight into the performance of new materials and designs of hip arthroplasties. Even the most rigorous in vitro testing will not accurately simulate the behavior of implant materials and new designs of prosthetic arthroplasties. Retrieval analysis has revealed such factors as the effects of gamma-in-air sterilisation of polyethylene, fatigue failure mechanisms of polymethylmethacrylate bone cement, fretting corrosion of Morse taper junctions, third body wear effects of both hard-on-hard and hard-on-soft bearing couples, and the effects of impingement of components on the full spectrum of bearing surfaces, none of which was predicted by pre-implantation in vitro testing of these materials and combinations. The temporal sequence of the retrieval process is approximately six years from first implantation through retrieval analysis, laboratory investigation, and publication of results, and thus, in addition to rigorous clinical evaluation, represents the true development and insight cycle for new designs and materials

Aims

Head-taper corrosion is a cause of failure in total hip arthroplasty (THA). Recent reports have described an increasing number of V40 taper failures with adverse local tissue reaction (ALTR). However, the real incidence of V40 taper damage and its cause remain unknown. The aim of this study was to evaluate the long-term incidence of ALTR in a consecutive series of THAs using a V40 taper and identify potentially related factors.

Aims

This study reports the ten-year wear rates, incidence of osteolysis, clinical outcomes, and complications of a multicentre randomized controlled trial comparing oxidized zirconium (OxZr) versus cobalt-chrome (CoCr) femoral heads with ultra-high molecular weight polyethylene (UHMWPE) and highly cross-linked polyethylene (XLPE) liners in total hip arthroplasty (THA).

Aims

Platelet-rich plasma (PRP) intra-articular injections may provide a simple and minimally invasive treatment for early-stage knee osteoarthritis (OA). This has led to an increase in its adoption as a treatment for knee OA, although there is uncertainty about its efficacy and benefit. We hypothesized that patients with early-stage symptomatic knee OA who receive multiple PRP injections will have better clinical outcomes than those receiving single PRP or placebo injections.

We investigated the antibiotic concentration in fresh-frozen femoral head allografts harvested from two groups of living donors. Ten samples were collected from patients with osteoarthritis of the hip and ten from those with a fracture of the neck of the femur scheduled for primary arthroplasty. Cefazolin (1 g) was administered as a pre-operative prophylactic antibiotic. After storage at −80°C for two weeks the pattern of release of cefazolin from morsellised femoral heads was evaluated by an in vitro broth elution assay using high-performance liquid chromatography. The bioactivity of the bone was further determined with an agar disc diffusion and standardised tube dilution bioassay. The results indicated that the fresh-frozen femoral heads contained cefazolin. The morsellised bone released cefazolin for up to four days. The concentration of cefazolin was significantly higher in the heads from patients with osteoarthritis of the hip than in those with a fracture. Also, in bioassays the bone showed inhibitory effects against bacteria. We concluded that allografts of morsellised bone from the femoral head harvested from patients undergoing arthroplasty of the hip contained cefazolin, which had been administered pre-operatively and they exhibited inhibitory effects against bacteria in vitro

Aims

This systematic review aims to compare the precision of component positioning, patient-reported outcome measures (PROMs), complications, survivorship, cost-effectiveness, and learning curves of MAKO robotic arm-assisted unicompartmental knee arthroplasty (RAUKA) with manual medial unicompartmental knee arthroplasty (mUKA).

Periprosthetic joint infection (PJI) is a difficult complication requiring a comprehensive eradication protocol. Cure rates have essentially stalled in the last two decades, using methods of antimicrobial cement joint spacers and parenteral antimicrobial agents. Functional spacers with higher-dose antimicrobial-loaded cement and antimicrobial-loaded calcium sulphate beads have emphasized local antimicrobial delivery on the premise that high-dose local antimicrobial delivery will enhance eradication. However, with increasing antimicrobial pressures, microbiota have responded with adaptive mechanisms beyond traditional antimicrobial resistance genes. In this review we describe adaptive resistance mechanisms that are relevant to the treatment of PJI. Some mechanisms are well known, but others are new. The objective of this review is to inform clinicians of the known adaptive resistance mechanisms of microbes relevant to PJI. We also discuss the implications of these adaptive mechanisms in the future treatment of PJI.

Cite this article: Bone Joint J 2022;104-B(5):575–580.

Aims

Highly polished stems with force-closed design have shown satisfactory clinical results despite being related to relatively high early migration. It has been suggested that the minimal thickness of cement mantles surrounding the femoral stem should be 2 mm to 4 mm to avoid aseptic loosening. The line-to-line cementing technique of the femoral stem, designed to achieve stem press-fit, challenges this opinion. We compared the migration of a highly polished stem with force-closed design by standard and line-to-line cementing to investigate whether differences in early migration of the stems occur in a clinical study.

Aims

The aim of this study was to investigate the outcome of periprosthetic fractures of the humerus and to assess the uniformity of the classifications used for these fractures (including those around elbow and/or shoulder arthroplasties) by performing a systematic review of the literature.

Aims. We sought to establish whether an oxidised zirconium (OxZr) femoral component causes less loss of polyethylene volume than a cobalt alloy (CoCr) femoral component in total knee arthroplasty. Materials and Methods. A total of 20 retrieved tibial inserts that had articulated with OxZr components were matched with 20 inserts from CoCr articulations for patient age, body mass index, length of implantation, and revision diagnosis. Changes in dimensions of the articular surfaces were compared with those of pristine inserts using laser scanning. The differences in volume between the retrieved and pristine surfaces of the two groups were calculated and compared. Results. The loss of polyethylene volume was 122 mm. 3. (standard deviation (. sd. ) 87) in the OxZr group and 170 mm. 3. (. sd. 96) in the CoCr group (p = 0.033). The volume loss in the OxZr group was also lower in the medial (72 mm. 3 . (. sd. 67) versus 92 mm. 3 . (. sd. 60); p = 0.096) and lateral (49 mm. 3 . (. sd. 36) versus 79 mm. 3 . (. sd. 61); p = 0.096) compartments separately, but these differences were not significant. Conclusion. Our results corroborate earlier findings from in vitro testing and visual retrieval analysis which suggest that polyethylene volume loss is lower with OxZr femoral components. Since both OxZr and CoCr are hard surfaces that would be expected to create comparable amounts of polyethylene creep, the differences in volume loss may reflect differences in the in vivo wear of these inserts. Cite this article: Bone Joint J 2017;99-B:793–8

Aims

Thresholds of acceptable early migration of the components in total knee arthroplasty (TKA) have traditionally ignored the effects of patient and implant factors that may influence migration. The aim of this study was to determine which of these factors are associated with overall longitudinal migration of well-fixed tibial components following TKA.

We have evaluated in vitro the accuracy of percutaneous and ultrasound registration as measured in terms of errors in rotation and version relative to the bony anterior pelvic plane in computer-assisted total hip replacement, and analysed the intra- and inter-observer reliability of manual or ultrasound registration. Four clinicians were asked to perform registration of the landmarks of the anterior pelvic plane on two cadavers. Registration was performed under four different conditions of acquisition. Errors in rotation were not significant. Version errors were significant with percutaneous methods (16.2°; p < 0.001 and 19.25° with surgical draping; p < 0.001), but not with the ultrasound acquisition (6.2°, p = 0.13). Intra-observer repeatability was achieved for all the methods. Inter-observer analysis showed acceptable agreement in the sagittal but not in the frontal plane. Ultrasound acquisition of the anterior pelvic plane was more reliable in vitro than the cutaneous digitisation currently used

Aims. The increased in vivo resistance to wear of highly crosslinked polyethylene (HXLPE) in total hip arthroplasty (THA) has led to an increased use of larger articulations which have been shown to reduce the incidence of early dislocation. To date, there are few reports of the wear of larger articulations using second generation HXLPE liners. Our prospective cohort study measured the bedding-in and early wear of large (36 mm and 40 mm diameter) articulations involving a second generation X3 HXLPE liner and compared our findings with previous clinical and in vitro studies of the same material. Patients and Methods. The proximal penetration of the femoral head five years post-operatively was measured for 15 patients using radiostereometric analysis (RSA). Results. The median proximal bedding-in within the first post-operative year was 0.022 mm (interquartile range (IQR) -0.050 to 0.091). The median proximal rate of wear between one and five years was -0.004 mm/year (IQR -0.021 to 0.022). The rates of proximal, medial, 2D or 3D wear between one and five years post-operatively of the X3 HXLPE liner did not increase with larger articulations compared with our previous study of 32 mm articulations. Conclusion. Although reassuring, the use of larger articulations requires continued monitoring to determine whether the low wear observed in the short-term continues to the mid- to long-term. Cite this article: Bone Joint J 2016;98-B:1604–10

Aims

This study compared the cobalt and chromium serum ion concentration of patients treated with two different metal-on-metal (MoM) hinged total knee arthroplasty (TKA) systems, as well as a titanium nitride (TiN)-coated variant.

Aims

Type 2 diabetes mellitus (T2DM) impairs bone strength and is a significant risk factor for hip fracture, yet currently there is no reliable tool to assess this risk. Most risk stratification methods rely on bone mineral density, which is not impaired by diabetes, rendering current tests ineffective. CT-based finite element analysis (CTFEA) calculates the mechanical response of bone to load and uses the yield strain, which is reduced in T2DM patients, to measure bone strength. The purpose of this feasibility study was to examine whether CTFEA could be used to assess the hip fracture risk for T2DM patients.

Implant-associated infection is a major source of morbidity in orthopaedic surgery. There has been extensive research into the development of materials that prevent biofilm formation, and hence, reduce the risk of infection. Silver nanoparticle technology is receiving much interest in the field of orthopaedics for its antimicrobial properties, and the results of studies to date are encouraging. Antimicrobial effects have been seen when silver nanoparticles are used in trauma implants, tumour prostheses, bone cement, and also when combined with hydroxyapatite coatings. Although there are promising results with in vitro and in vivo studies, the number of clinical studies remains small. Future studies will be required to explore further the possible side effects associated with silver nanoparticles, to ensure their use in an effective and biocompatible manner. Here we present a review of the current literature relating to the production of nanosilver for medical use, and its orthopaedic applications. Cite this article: Bone Joint J 2015; 97-B:582–9

The purpose of this study was to examine the effects of hyaluronic acid supplementation on chondrocyte metabolism in vitro. The clinical benefits of intra-articular hyaluronic acid injections are thought to occur through improved joint lubrication. Recent findings have shown that exogenous hyaluronic acid is incorporated into articular cartilage where it may have a direct biological effect on chondrocytes through CD44 receptors. Bovine articular chondrocytes were isolated and seeded into alginate constructs. These were cultured in medium containing hyaluronic acid at varying concentrations. Samples were assayed for biochemical and histological changes. There was a dose-dependent response to the exposure of hyaluronic acid to bovine articular chondrocytes in vitro. Low concentrations of hyaluronic acid (0.1 mg/mL and 1 mg/mL) significantly increase DNA, sulphated glycosaminoglycan and hydroxyproline synthesis. Immunohistology confirmed the maintenance of cell phenotype with increased matrix deposition of chondroitin-6-sulphate and collagen type II. These findings confirm a stimulatory effect of hyaluronic acid on chondrocyte metabolism

Aims

Stemless humeral implants have been developed to overcome stem-related complications in total shoulder arthroplasty (TSA). However, stemless implant designs may hypothetically result in less stable initial fixation, potentially affecting long-term survival. The aim of this study is to investigate early fixation and migration patterns of the stemless humeral component of the Simpliciti Shoulder System and to evaluate clinical outcomes.

Aims

Higher osteoblastic bone activity is expected in aseptic loosening and painful unicompartmental knee arthroplasty (UKA). However, insights into normal bone activity patterns after medial UKAs are lacking. The aim of this study was to identify the evolution in bone activity pattern in well-functioning medial mobile-bearing UKAs.

Aims. Demineralised bone matrix (DBM) is rarely used for the local delivery of prophylactic antibiotics. Our aim, in this study, was to show that a graft with a bioactive glass and DBM combination, which is currently available for clinical use, can be loaded with tobramycin and release levels of antibiotic greater than the minimum inhibitory concentration for Staphylococcus aureus without interfering with the bone healing properties of the graft, thus protecting the graft and surrounding tissues from infection. Materials and Methods. Antibiotic was loaded into a graft and subsequently evaluated for drug elution kinetics and the inhibition of bacterial growth. A rat femoral condylar plug model was used to determine the effect of the graft, loaded with antibiotic, on bone healing. Results. We found that tobramycin loaded into a graft composed of bioglass and DBM eluted antibiotic above the minimum inhibitory concentration for three days in vitro. It was also found that the antibiotic loaded into the graft produced no adverse effects on the bone healing properties of the DBM at a lower level of antibiotic. Conclusion. This antibiotic-loaded bone void filler may represent a promising option for the delivery of local antibiotics in orthopaedic surgery. Cite this article: Bone Joint J 2016;98-B:1126–31

We have examined whether primary human muscle-derived cells can be used in ex vivo gene therapy to deliver BMP-2 and to produce bone in vivo. Two in vitro experiments and one in vivo experiment were used to determine the osteocompetence and BMP-2 secretion capacity of cells isolated from human skeletal muscle. We isolated five different populations of primary muscle cells from human skeletal muscle in three patients. In the first in vitro experiment, production of alkaline phosphatase by the cells in response to stimulation by rhBMP-2 was measured and used as an indicator of cellular osteocompetence. In the second, secretion of BMP-2 was measured after the cell populations had been transduced by an adenovirus encoding for BMP-2. In the in vivo experiment, the cells were cotransduced with a retrovirus encoding for a nuclear localised β-galactosidase gene and an adenovirus encoding for BMP-2. The cotransduced cells were then injected into the hind limbs of severe combined immune-deficient (SCID) mice and analysed radiographically and histologically. The nuclear localised β-galactosidase gene allowed identification of the injected cells in histological specimens. In the first in vitro experiment, the five different cell populations all responded to in vitro stimulation of rhBMP-2 by producing higher levels of alkaline phosphatase when compared with non-stimulated cells. In the second, the five different cell populations were all successfully transduced by an adenovirus to express and secrete BMP-2. The cells secreted between 444 and 2551 ng of BMP-2 over three days. In the in vivo experiment, injection of the transduced cells into the hind-limb musculature of SCID mice resulted in the formation of ectopic bone at 1, 2, 3 and 4 weeks after injection. Retroviral labelling of the cell nuclei showed labelled human muscle-derived cells occupying locations of osteoblasts in the ectopic bone, further supporting their osteocompetence. Cells from human skeletal muscle, because of their availability to orthopaedic surgeons, their osteocompetence, and their ability to express BMP-2 after genetic engineering, are an attractive cell population for use in BMP-2 gene therapy approaches

Periprosthetic joint infection (PJI) is one of the most dreaded complications after arthroplasty surgery; thus numerous approaches have been undertaken to equip metal surfaces with antibacterial properties. Due to its antimicrobial effects, silver is a promising coating for metallic surfaces, and several types of silver-coated arthroplasty implants are in clinical use today. However, silver can also exert toxic effects on eukaryotic cells both in the immediate vicinity of the coated implants and systemically. In most clinically-used implants, silver coatings are applied on bulk components that are not in direct contact with bone, such as in partial or total long bone arthroplasties used in tumour or complex revision surgery. These implants differ considerably in the coating method, total silver content, and silver release rates. Safety issues, such as the occurrence of argyria, have been a cause for concern, and the efficacy of silver coatings in terms of preventing PJI is also controversial. The application of silver coatings is uncommon on parts of implants intended for cementless fixation in host bone, but this option might be highly desirable since the modification of implant surfaces in order to improve osteoconductivity can also increase bacterial adhesion. Therefore, an optimal silver content that inhibits bacterial colonization while maintaining osteoconductivity is crucial if silver were to be applied as a coating on parts intended for bone contact. This review summarizes the different methods used to apply silver coatings to arthroplasty components, with a focus on the amount and duration of silver release from the different coatings; the available experience with silver-coated implants that are in clinical use today; and future strategies to balance the effects of silver on bacteria and eukaryotic cells, and to develop silver-coated titanium components suitable for bone ingrowth.

Cite this article: Bone Joint J 2021;103-B(3):423–429.

We have assessed the different adhesive properties of some of the most common bacteria associated with periprosthetic joint infection on various types of ultra high molecular Weight Polyethylene (UHMWPE). Quantitative in vitro analysis of the adhesion of biofilm producing strains of Staphylococcus aureus and Escherichia coli to physically and chemically characterised standard UHMWPE (PE), vitamin E blended UHMWPE (VE-PE) and oxidised UHMWPE (OX-PE) was performed using a sonication protocol. A significant decreased bacterial adhesion was registered for both strains on VE-PE, in comparison with that observed on PE, within 48 hours of observation (S. aureus p = 0.024 and E. coli p = 0.008). Since Vitamin E reduces bacterial adhesive ability, VE-stabilised UHMWPE could be valuable in joint replacement by presenting excellent mechanical properties, while reducing bacterial adhesiveness. Cite this article: Bone Joint J 2014;96-B:497–501

Aims

Dual mobility implants in total hip arthroplasty are designed to increase the functional head size, thus decreasing the potential for dislocation. Modular dual mobility (MDM) implants incorporate a metal liner (e.g. cobalt-chromium alloy) in a metal shell (e.g. titanium alloy), raising concern for mechanically assisted crevice corrosion at the modular liner-shell connection. We sought to examine fretting and corrosion on MDM liners, to analyze the corrosion products, and to examine histologically the periprosthetic tissues.

Aims

Surgeons commonly resect additional distal femur during primary total knee arthroplasty (TKA) to correct a flexion contracture, which leads to femoral joint line elevation. There is a paucity of data describing the effect of joint line elevation on mid-flexion stability and knee kinematics. Thus, the goal of this study was to quantify the effect of joint line elevation on mid-flexion laxity.

Articular cartilage repair remains a challenge to surgeons and basic scientists. The field of tissue engineering allows the simultaneous use of material scaffolds, cells and signalling molecules to attempt to modulate the regenerative tissue. This review summarises the research that has been undertaken to date using this approach, with a particular emphasis on those techniques that have been introduced into clinical practice, via in vitro and preclinical studies