Recently, femoroacetabular impingement has been recognised as a cause of early osteoarthritis. There are two mechanisms of impingement: 1) cam impingement caused by a non-spherical head and 2) pincer impingement caused by excessive acetabular cover. We hypothesised that both mechanisms result in different patterns of articular damage. Of 302 analysed hips only 26 had an isolated cam and 16 an isolated pincer impingement. Cam impingement caused damage to the anterosuperior acetabular cartilage with separation between the labrum and cartilage. During flexion, the cartilage was sheared off the bone by the non-spherical femoral head while the labrum remained untouched. In pincer impingement, the cartilage damage was located circumferentially and included only a narrow strip. During movement the labrum is crushed between the acetabular rim and the femoral neck causing degeneration and ossification. Both cam and pincer impingement lead to osteoarthritis of the hip. Labral damage indicates ongoing impingement and rarely occurs alone

Previous research has shown an increase in chromosomal aberrations in patients with worn implants. The type of aberration depended on the type of metal alloy in the prosthesis. We have investigated the metal-specific difference in the level of DNA damage (DNA stand breaks and alkali labile sites) induced by culturing human fibroblasts in synovial fluid retrieved at revision arthroplasty. All six samples from revision cobalt-chromium metal-on-metal and four of six samples from cobalt-chromium metal-on-polyethylene prostheses caused DNA damage. By contrast, none of six samples from revision stainless-steel metal-on-polyethylene prostheses caused significant damage. Samples of cobalt-chromium alloy left to corrode in phosphate-buffered saline also caused DNA damage and this depended on a synergistic effect between the cobalt and chromium ions. Our results further emphasise that epidemiological studies of orthopaedic implants should take account of the type of metal alloy used

We examined stainless-steel, cobalt-chrome, titanium and alumina and zirconia ceramic femoral heads retrieved at revision surgery. All the heads had articulated against ultra-high-molecular-weight-polyethylene (UHMWPE) acetabular cups. We studied the simulation of third-body damage and the wear of UHMWPE against the various materials used for the heads. The surfaces of the retrieved heads were analysed using a two-dimensional contacting profilometer. Third-body damage was characterised by the mean height of the scratches above the mean line (R. pm. ). The alumina ceramic and zirconia ceramic retrieved heads were found to have significantly less damage. In laboratory studies the ceramics were also more resistant to simulated third-body damage than the metal alloys. We studied the wear of UHMWPE against the damaged counterfaces in simple configuration tests. The damaged ceramics produced less polyethylene wear than the damaged metal counterfaces. The wear factor of UHMWPE against the damaged materials was dependent on the amount of damage to the counterface (R. p. ). Our study has shown the benefit of using the harder and more damage-resistant ceramic materials for femoral heads

Using the transverse processes of fresh porcine lumbar spines as an experimental model we evaluated the heat generated by a rotating burr of a high-speed drill in cutting the bone. The temperature at the drilled site reached 174°C with a diamond burr and 77°C with a steel burr. With water irrigation at a flow rate of 540 ml/hr an effective reduction in the temperature was achieved whereas irrigation with water at 180 ml/hr was much less effective. There was a significant negative correlation between the thickness of the residual bone and the temperature measured at its undersurface adjacent to the drilling site (p < 0.001). Our data suggest that tissues neighbouring the drilled bone, especially nerve roots, can be damaged by the heat generated from the tip of a high-speed drill. Nerve-root palsy, one of the most common complications of cervical spinal surgery, may be caused by thermal damage to nerve roots arising in this manner

Wear debris was extracted from 21 worn hip and knee replacements. Its mutagenic effects were tested on human cells in tissue culture using the micronucleus assay and fluorescent in situ hybridisation. The extracted wear debris increased the level of micronuclei in a linear dose-dependent manner but with a tenfold difference between samples. The concentration of titanium +/− vanadium and aluminium within the wear debris was linearly related both to the level of centromere-positive micronuclei in tissue culture, indicating an aneuploid event, and to the level of aneuploidy in vivo in peripheral blood lymphocytes. The concentration of cobalt and chromium +/− nickel and molybdenum in the wear debris correlated with the total index of micronuclei in tissue culture, both centromere-positive and centromere-negative i.e. both chromosomal breakage and aneuploidy events. The results show that wear debris can damage chromosomes in a dose-dependent manner which is specific to the type of metal. The results from studies in vitro correlate with those in vivo and suggest that the wear debris from a worn implant is at least partly responsible for the chromosomal damage which is seen in vivo

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

Implantation of autologous chondrocytes and matrix autologous chondrocytes are techniques of cartilage repair used in the young adult knee which require harvesting of healthy cartilage and which may cause iatrogenic damage to the joint. This study explores alternative sources of autologous cells. Chondrocytes obtained from autologous bone-marrow-derived cells and those from the damaged cartilage within the lesion itself are shown to be viable alternatives to harvest-derived cells. A sufficient number and quality of cells were obtained by the new techniques and may be suitable for autologous chondrocyte and matrix autologous chondrocyte implantation

We have developed an animal model to examine the formation of heterotopic ossification using standardised muscular damage and implantation of a beta-tricalcium phosphate block into a hip capsulotomy wound in Wistar rats. The aim was to investigate how cells originating from drilled femoral canals and damaged muscles influence the formation of heterotopic bone. The femoral canal was either drilled or left untouched and a tricalcium phosphate block, immersed either in saline or a rhBMP-2 solution, was implanted. These implants were removed at three and 21 days after the operation and examined histologically, histomorphometrically and immunohistochemically. Bone formation was seen in all implants in rhBMP-2-immersed, whereas in those immersed in saline the process was minimal, irrespective of drilling of the femoral canals. Bone mineralisation was somewhat greater in the absence of drilling with a mean mineralised volume to mean total volume of 18.2% (. sd. 4.5) versus 12.7% (. sd. 2.9, p < 0.019), respectively. Our findings suggest that osteoinductive signalling is an early event in the formation of ectopic bone. If applicable to man the results indicate that careful tissue handling is more important than the prevention of the dissemination of bone cells in order to avoid heterotopic ossification

We have studied damage to the tibial articular surface after replacement of the femoral surface in dogs. We inserted pairs of implants made of alumina, titanium and polyvinyl alcohol (PVA) hydrogel on titanium fibre mesh into the femoral condyles. The two hard materials caused marked pathological changes in the articular cartilage and menisci, but the hydrogel composite replacement caused minimal damage. The composite osteochondral device became rapidly attached to host bone by ingrowth into the supporting mesh. We discuss the clinical implications of the possible use of this material in articular resurfacing and joint replacement

We dissected 20 cadaver hips in order to investigate the anatomy and excursion of the trochanteric muscles in relation to the posterior approach for total hip replacement. String models of each muscle were created and their excursion measured while the femur was moved between its anatomical position and the dislocated position. The position of the hip was determined by computer navigation. In contrast to previous studies which showed a separate insertion of piriformis and obturator internus, our findings indicated that piriformis inserted onto the superior and anterior margins of the greater trochanter through a conjoint tendon with obturator internus, and had connections to gluteus medius posteriorly. Division of these connections allowed lateral mobilisation of gluteus medius with minimal retraction. Analysis of the excursion of these muscles revealed that positioning the thigh for preparation of the femur through this approach elongated piriformis to a maximum of 182%, obturator internus to 185% and obturator externus to 220% of their resting lengths, which are above the thresholds for rupture of these muscles. Our findings suggested that gluteus medius may be protected from overstretching by release of its connection with the conjoint tendon. In addition, failure to detach piriformis or the obturators during a posterior approach for total hip replacement could potentially produce damage to these muscles because of over-stretching, obturator externus being the most vulnerable

Surgical reconstruction of articular surfaces by transplantation of osteochondral autografts has shown considerable promise in the treatment of focal articular lesions. During mosaicplasty, each cylindrical osteochondral graft is centred over the recipient hole and delivered by impacting the articular surface. Impact loading of articular cartilage has been associated with structural damage, loss of the viability of chondrocytes and subsequent degeneration of the articular cartilage. We have examined the relationship between single-impact loading and chondrocyte death for the specific confined-compression boundary conditions of mosaicplasty and the effect of repetitive impact loading which occurs during implantation of the graft on the resulting viability of the chondrocytes. Fresh bovine and porcine femoral condyles were used in this experiment. The percentage of chondrocyte death was found to vary logarithmically with single-impact energy and was predicted more strongly by the mean force of the impact rather than by the number of impacts required during placement of the graft. The significance of these results in regard to the surgical technique and design features of instruments for osteochondral transplantation is discussed

Aseptic loosening is a major cause of failure of total hip arthroplasty. The adverse tissue response to prosthetic wear particles, with activation of cytokine and prostanoid production, contributes to bone loss around the implants. We have investigated the possibility that inducible nitric oxide synthase (iNOS) and cyclo-oxygenase-2 (COX-2) are expressed in macrophages in the pseudomembrane at the bone-implant interface, thereby contributing to the periprosthetic bone resorption. We also assessed whether peroxynitrite, a nitric oxide (NO)-derived oxidant associated with cellular injury, is generated in the membrane. Enzymatic activity of iNOS was measured using the arginine-citrulline assay technique and prostaglandin E. 2. (PGE. 2. ), as an indicator of COX-2 activity, was measured using an enzyme immunoassay. Cellular immunoreactivity for iNOS, nitrotyrosine (a marker of peroxynitrite-induced cellular injury) and COX-2 was assessed by quantitative peroxidase immunocytochemistry while immunofluorescence methods were used for subsequent co-localisation studies with CD68. +. macrophages. The presence of calcium-independent iNOS activity and PGE. 2. production was confirmed in the homogenized interface membrane. Immunocytochemistry showed that periprosthetic CD68. +. wear-debris-laden macrophages were the most prominent cell type immunoreactive for iNOS, nitrotyrosine and COX-2. Other periprosthetic inflammatory and resident cell types were also found to immunolocalise nitrotyrosine thereby suggesting peroxynitrite-induced protein nitrosylation and cellular damage not only in NO-producing CD68. +. macrophages, but also in their neighbouring cells. These data indicate that both iNOS and COX-2 are expressed by CD68. +. macrophages in the interface membrane and peroxynitrite-induced cellular damage is evident in such tissue. If high-output NO and peroxynitrite generation were to cause macrophage cell death, this would result in the release of phagocytosed wear debris into the extracellular matrix. A detrimental cycle of events would then be established with further phagocytosis by newly-recruited inflammatory cells and subsequent NO, peroxynitrite and prostanoid synthesis. Since both NO and have been implicated in the induction and PGE. 2. maintenance of chronic inflammation with resulting loss of bone, and peroxynitrite in the pathogenesis of disease states, they may be central to the pathogenesis of aseptic loosening

We compared the quality of debridement of chondral lesions performed by four arthroscopic (SH, shaver; CU, curette; SHCU, shaver and curette; BP, bipolar electrodes) and one open technique (OPEN, scalpel and curette) which are used prior to autologous chondrocyte implantation (ACI). The ex vivo simulation of all five techniques was carried out on six juvenile equine stifle joints. The OPEN, SH and SHCU techniques were tested on knees harvested from six adult human cadavers. The most vertical walls with the least adjacent damage to cartilage were obtained with the OPEN technique. The CU and SHCU methods gave inferior, but still acceptable results whereas the SH technique alone resulted in a crater-like defect and the BP method undermined the cartilage wall. The subchondral bone was severely violated in all the equine samples which might have been peculiar to this model. The predominant depth of the debridement in the adult human samples was at the level of the calcified cartilage. Some minor penetrations of the subchondral end-plate were induced regardless of the instrumentation used. Our study suggests that not all routine arthroscopic instruments are suitable for the preparation of a defect for ACI. We have shown that the preferred debridement technique is either open or arthroscopically-assisted manual curettage. The use of juvenile equine stifles was not appropriate for the study of the cartilage-subchondral bone interface

The aim of this study was to investigate the occurrence of tissue hypoxia and apoptosis at different stages of tendinopathy and tears of the rotator cuff. We studied tissue from 24 patients with eight graded stages of either impingement (mild, moderate and severe) or tears of the rotator cuff (partial, small, medium, large and massive) and three controls. Biopsies were analysed using three immunohistochemical techniques, namely antibodies against HIF-1α (a transcription factor produced in a hypoxic environment), BNip3 (a HIF-1α regulated pro-apoptotic protein) and TUNEL (detecting DNA fragmentation in apoptosis). The HIF-1α expression was greatest in mild impingement and in partial, small, medium and large tears. BNip3 expression increased significantly in partial, small, medium and large tears but was reduced in massive tears. Apoptosis was increased in small, medium, large and massive tears but not in partial tears. These findings reveal evidence of hypoxic damage throughout the spectrum of pathology of the rotator cuff which may contribute to loss of cells by apoptosis. This provides a novel insight into the causes of degeneration of the rotator cuff and highlights possible options for treatment

Ischaemic preconditioning is a process by which exposure of a tissue to a short period of non-damaging ischaemic stress leads to resistance to the deleterious effects of a subsequent prolonged ischaemic stress. It has been extensively described in the heart, but few studies have examined the possibility that it can occur in skeletal muscle. We have used a rat model of ischaemia of one limb to examine this possibility. Exposure of the hind limb to a period of ischaemia of five minutes and reperfusion for five minutes significantly protected the tibialis anterior muscle against the structural damage induced by a subsequent period of limb ischaemia for four hours and reperfusion for one hour. This protection was evident on examination of the muscle by both light and electron microscopy. Longer or shorter times of prior ischaemia had no effect

Secondary sterilisation of allograft bone by gamma irradiation is common, but the conditions under which it is performed vary between tissue banks. Some do so at room temperature, others while the bone is frozen. Bone is made brittle by irradiation because of the destruction of collagen alpha chains, probably mediated by free radicals generated from water molecules. Freezing reduces the mobility of water molecules and may therefore decrease the production of free radicals. We found that bone irradiated at −78°C was less brittle and had less collagen damage than when irradiated at room temperature. These findings may have implications for bone-banking

The long-term biological effects of wear debris are unknown. We have investigated whether there is any evidence of cumulative mutagenic damage in peripheral blood lymphocytes of patients undergoing revision arthroplasty of predominantly metal-on-plastic total hip replacements compared with those at primary arthroplasty. There was a threefold increase in aneuploidy and a twofold increase in chromosomal translocations which could not be explained by the confounding variables of smoking, gender, age and diagnostic radiographs. In the patients with TiVaAl prostheses there was a fivefold increase in aneuploidy but no increase in chromosomal translocations. By contrast, in patients with cobalt-chrome prostheses there was a 2.5-fold increase in aneuploidy and a 3.5-fold increase in chromosomal translocations. In six patients with stainless-steel prostheses there was no increase in either aneuploidy or chromosomal translocations. Our results suggest that future epidemiological studies of the putative long-term risks of joint replacement should take into account the type of alloy used in the prosthesis

We obtained medial and lateral subchondral cancellous bone specimens from ten human postmortem proximal tibiae with early osteoarthritis (OA) and ten normal age- and gender-matched proximal tibiae. The specimens were scanned by micro-CT and the three-dimensional microstructural properties were quantified. Medial OA cancellous bone was significantly thicker and markedly plate-like, but lower in mechanical properties than normal bone. Similar microstructural changes were also observed for the lateral specimens from OA bone, although there had been no sign of cartilage damage. The increased trabecular thickness and density, but relatively decreased connectivity suggest a mechanism of bone remodelling in early OA as a process of filling trabecular cavities. This process leads to a progressive change of trabeculae from rod-like to plate-like, the opposite to that of normal ageing. The decreased mechanical properties of subchondral cancellous bone in OA, which are due to deterioration in architecture and density, indicate poor bone quality

We studied the various drill bits available for engineering purposes, and compared them with standard orthopaedic drill bits, using continuous temperature recording at 0.5 mm, 1.0 mm and 1.5 mm from the edge of a 2.5 mm hole as it was drilled in fresh cadaver human tibia. We found that some commercially available drill bits performed better than their orthopaedic equivalents, producing significantly less thermal injury to the surrounding bone and halving the force required for cortical penetration. Our work suggests that the optimal bit for orthopaedic purposes should have a split point and a quick helix. Theoretical knowledge of cutting technology predicts that the addition of a parabolic flute will further reduce thermal damage. Further work is being done on other drill sizes used in orthopaedic practice and on new custom-designed bits

Ischaemia-reperfusion injury (IRI) is caused by endothelial and subendothelial damage by neutrophil-derived oxidants. Vitamin C is an antioxidant which attenuates endothelial injury after IRI. Our aim was to evaluate the effect of oral vitamin C in the prevention of IRI in skeletal muscle. We used a model of cross-clamping (3 hours) and reperfusion (1 hour) of the cremaster muscle in rats. Muscle function was assessed electrophysiologically by electrical field stimulation. Infiltration by neutrophils was determined by the activity of tissue myeloperoxidase (MPO) and tissue oedema by the wet-to-dry ratio. Neutrophil respiratory burst activity was measured in control animals and groups pretreated with vitamin C. IRI significantly decreased muscle function and increased muscle neutrophil MPO activity and muscle oedema. Pretreatment with vitamin C preserved muscle function and reduced tissue oedema and neutrophil infiltration. Neutrophil respiratory burst activity was reduced in the group treated with vitamin C compared with the control group. We conclude that pretreatment with oral vitamin C protects against acute muscle IRI, possibly by attenuating neutrophil respiratory burst activity