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

Aims. The aim of this study was to investigate whether wear and backside deformation of polyethylene (PE) tibial inserts may influence the cement cover of tibial trays of explanted total knee arthroplasties (TKAs). Methods. At our retrieval centre, we measured changes in the wear and deformation of PE inserts using coordinate measuring machines and light microscopy. The amount of cement cover on the backside of tibial trays was quantified as a percentage of the total surface. The study involved data from the explanted fixed-bearing components of four widely used contemporary designs of TKA (Attune, NexGen, Press Fit Condylar (PFC), and Triathlon), revised for any indication, and we compared them with components that used previous generations of PE. Regression modelling was used to identify variables related to the amount of cement cover on the retrieved trays. Results. A total of 114 explanted fixed-bearing TKAs were examined. This included 76 used with contemporary PE inserts which were compared with 15 used with older generation PEs. The Attune and NexGen (central locking) trays were found to have significantly less cement cover than Triathlon and PFC trays (peripheral locking group) (p = 0.001). The median planicity values of the PE inserts used with central locking trays were significantly greater than of those with peripheral locking inserts (205 vs 85 microns; p < 0.001). Attune and NexGen inserts had a characteristic pattern of backside deformation, with the outer edges of the PE deviating inferiorly, leaving the PE margins as the primary areas of articulation. Conclusion. Explanted TKAs with central locking mechanisms were significantly more likely to debond from the cement mantle. The PE inserts of these designs showed characteristic patterns of deformation, which appeared to relate to the manufacturing process and may be exacerbated in vivo. This pattern of deformation was associated with PE wear occurring at the outer edges of the articulation, potentially increasing the frictional torque generated at this interface. Cite this article: Bone Joint J 2021;103-B(12):1791–1801

Aims. The aims of this study were to develop an in vivo model of periprosthetic joint infection (PJI) in cemented hip hemiarthroplasty, and to monitor infection and biofilm formation in real-time. Methods. Sprague-Dawley rats underwent cemented hip hemiarthroplasty via the posterior approach with pre- and postoperative gait assessments. Infection with Staphylococcus aureus Xen36 was monitored with in vivo photoluminescent imaging in real-time. Pre- and postoperative gait analyses were performed and compared. Postmortem micro (m) CT was used to assess implant integration; field emission scanning electron microscopy (FE-SEM) was used to assess biofilm formation on prosthetic surfaces. Results. All animals tolerated surgery well, with preservation of gait mechanics and weightbearing in control individuals. Postoperative in vivo imaging demonstrated predictable evolution of infection with logarithmic signal decay coinciding with abscess formation. Postmortem mCT qualitative volumetric analysis showed high contact area and both cement-bone and cement-implant interdigitation. FE-SEM revealed biofilm formation on the prosthetic head. Conclusion. This study demonstrates the utility of a new, high-fidelity model of in vivo PJI using cemented hip hemiarthroplasty in rats. Inoculation with bioluminescent bacteria allows for non-invasive, real-time monitoring of infection. Cite this article: Bone Joint J 2021;103-B(7 Supple B):9–16

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. Methods. A total of 60 retrieved liners were subjectively scored for fretting and corrosion. The corrosion products from the three most severely corroded implants were removed from the implant surface, imaged using scanning electron microscopy, and analyzed using Fourier-transform infrared spectroscopy. Results. Fretting was present on 88% (53/60) of the retrieved liners, and corrosion was present on 97% (58/60). Fretting was most often found on the lip of the taper at the transition between the lip and the dome regions. Macrophages and particles reflecting an innate inflammatory reaction to corrosion debris were noted in six of the 48 cases for which periprosthetic tissues were examined, and all were associated with retrieved components that had high corrosion scores. Conclusion. Our results show that corrosion occurs at the interface between MDM liners and shells and that it can be associated with reactions in the local tissues, suggesting continued concern that this problem may become clinically important with longer-term use of these implants. Cite this article: Bone Joint J 2021;103-B(7):1238–1246

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

Conventional amputation prostheses rely on the attachment of the socket to the stump, which may lead to soft-tissue complications. Intraosseous transcutaneous amputation prostheses (ITAPs) allow direct loading of the skeleton, but their success is limited by infection resulting from breaching of the skin at the interface with the implant. Keratinocytes provide the skin’s primary barrier function, while hemidesmosomes mediate their attachment to natural ITAP analogues. Keratinocytes must attach directly to the surface of the implant. We have assessed the proliferation, morphology and attachment of keratinocytes to four titaniumalloy surfaces in order to determine the optimal topography in vitro. We used immunolocalisation of adhesion complex components, scanning electron microscopy and transmission electron microscopy to assess cell parameters. We have shown that the proliferation, morphology and attachment of keratinocytes are affected by the surface topography of the biomaterials used to support their growth. Smoother surfaces improved adhesion. We postulate that a smooth topography at the point of epithelium-ITAP contact could increase attachment in vivo, producing an effective barrier of infection

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.

Ovine articular chondrocytes were isolated from cartilage biopsy and culture expanded in vitro. Approximately 30 million cells per ml of cultured chondrocytes were incorporated with autologous plasma-derived fibrin to form a three-dimensional construct. Full-thickness punch hole defects were created in the lateral and medial femoral condyles. The defects were implanted with either an autologous ‘chondrocyte-fibrin’ construct (ACFC), autologous chondrocytes (ACI) or fibrin blanks (AF) as controls. Animals were killed after 12 weeks. The gross appearance of the treated defects was inspected and photographed. The repaired tissues were studied histologically and by scanning electron microscopy analysis. All defects were assessed using the International Cartilage Repair Society (ICRS) classification. Those treated with ACFC, ACI and AF exhibited median scores which correspond to a nearly-normal appearance. On the basis of the modified O’Driscoll histological scoring scale, ACFC implantation significantly enhanced cartilage repair compared to ACI and AF. Using scanning electron microscopy, ACFC and ACI showed characteristic organisation of chondrocytes and matrices, which were relatively similar to the surrounding adjacent cartilage. Implantation of ACFC resulted in superior hyaline-like cartilage regeneration when compared with ACI. If this result is applicable to humans, a better outcome would be obtained than by using conventional ACI

1. The fibrillar networks of adult human articular cartilage, taken from femoral and acetabular specimens, have been systematically examined by scanning electron microscopy. The internal structures revealed by rupturing the tissue were compared with published findings from transmission electron microscope studies. 2. Though this technique demonstrated the internal fibrillar appearance of cartilage to a remarkable degree, it had several attendant limitations. On final drying, specimens generally exhibited shrinkage which varied within wide limits; this could have altered the internal architecture to some extent. In addition, the rupturing technique, which at the time of this investigation was the only satisfactory method of revealing the fibrillar cartilage structure, may well have had a great influence on the fibril orientations. 3. The fibrils revealed no characteristic collagen periodicity and were considerably thicker than those observed by transmission electron microscopy. It is suggested that a coating of mucin on the collagen fibrils might account for this. 4. At low magnifications the torn layers in the fractured surfaces extended radially from the calcified zone and turned obliquely at or near the articular surface to merge with the distinctly layered superficial zone, thus forming arcade-like structures. That these were not artefacts produced by the fracturing technique was shown by their similarity to the classical arcade pattern of light microscopy. However, the factor which governed the direction of these planes of weakness, be it collagen, mucopolysaccharides or cells, could not be satisfactorily determined. 5. At higher magnifications only three regions of distinct fibrillar organisation could be identified: 1) a surface layer consisting of a random fibrillar network; 2) a superficial zone composed of layers of fibrillar network, intersecting and overlapping in planes parallel to the surface; and 3) elsewhere below the superficial zone a network of virtually random fibrils which extended to the calcified region with apparently little variation in thickness or density. There was little variation from this pattern even in aged fibrillated specimens. 6. At the lower magnification range the scanning electron microscope has revealed the arcade pattern described by light microscopy, while at the higher magnifications the fibrillar organisation as seen by scanning electron microscopy correlated well with the concepts developed by transmission electron microscopy, that is, a random network of fibrils overlaid at the articular surface by a membrane-like system of bundled fibrils. 7. A possible role in the transmission of joint forces is outlined for the above fibrillar organisation

Aims

Low-grade central osteosarcoma (LGCOS), a rare type of osteosarcoma, often has misleading radiological and pathological features that overlap with those of other bone tumours, thereby complicating diagnosis and treatment. We aimed to analyze the clinical, radiological, and pathological features of patients with LGCOS, with a focus on diagnosis, treatment, and outcomes.

Periprosthetic joint infection (PJI) remains an extremely challenging complication. We have focused on this issue more over the last decade than previously, but there are still many unanswered questions. We now have a workable definition that everyone should align to, but we need to continue to focus on identifying the organisms involved. Surgical strategies are evolving and care is becoming more patient-centred. There are some good studies under way. There are, however, still numerous problems to resolve, and the challenge of PJI remains a major one for the orthopaedic community. This annotation provides some up-to-date thoughts about where we are, and the way forward. There is still scope for plenty of research in this area.

Cite this article: Bone Joint J 2022;104-B(11):1193–1195.

Aims. Compartment syndrome results from increased intra-compartmental pressure (ICP) causing local tissue ischaemia and cell death, but the systemic effects are not well described. We hypothesised that compartment syndrome would have a profound effect not only on the affected limb, but also on remote organs. Methods. Using a rat model of compartment syndrome, its systemic effects on the viability of hepatocytes and on inflammation and circulation were directly visualised using intravital video microscopy. Results. We found that hepatocellular injury was significantly higher in the compartment syndrome group (192 PI-labelled cells/10. -1 . mm. 3. , standard error of the mean (. sem. ) 51) compared with controls (30 PI-labelled cells/10. -1 . mm. 3. , . sem . 12, p < 0.01). The number of adherent venular white blood cells was significantly higher for the compartment syndrome group (5 leukocytes/30s/10 000 μm. 2. , . sem 1. ) than controls (0.2 leukocytes/30 s/10 000 μm. 2. , . sem . 0.2, p < 0.01). Volumetric blood flow was not significantly different between the two groups, although there was an increase in the heterogeneity of perfusion. Conclusions. Compartment syndrome can be accompanied by severe systemic inflammation and end organ damage. This study provides evidence of the relationship between compartment syndrome in a limb and systemic inflammation and dysfunction in a remote organ. Cite this article: Bone Joint J 2016; 98-B:1132–7

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

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

The mammalian growth plate is a complex structure which is essential for the elongation of long bones. However, an understanding of how the growth plate functions at the cellular level is lacking. This review, summarises the factors involved in growth-plate regulation, its failure and the consequence of injury. We also describe some of the cellular mechanisms which underpin the increase in volume of the growth-plate chondrocyte which is the major determinant of the rate and extent of bone lengthening. We show how living in situ chondrocytes can be imaged using 2-photon laser scanning microscopy to provide a quantitative analysis of their volume. This approach should give better understanding of the cellular control of bone growth in both healthy and failed growth plates

The aim of this study was to determine whether exposure of human articular cartilage to hyperosmotic saline (0.9%, 600 mOsm) reduces in situ chondrocyte death following a standardised mechanical injury produced by a scalpel cut compared with the same assault and exposure to normal saline (0.9%, 285 mOsm). Human cartilage explants were exposed to normal (control) and hyperosmotic 0.9% saline solutions for five minutes before the mechanical injury to allow in situ chondrocytes to respond to the altered osmotic environment, and incubated for a further 2.5 hours in the same solutions following the mechanical injury. Using confocal laser scanning microscopy, we identified a sixfold (p = 0.04) decrease in chondrocyte death following mechanical injury in the superficial zone of human articular cartilage exposed to hyperosmotic saline compared with normal saline. These data suggest that increasing the osmolarity of joint irrigation solutions used during open and arthroscopic articular surgery may reduce chondrocyte death from surgical injury and could promote integrative cartilage repair

We describe a cohort of patients with a high rate of mid-term failure following Kinemax Plus total knee replacement inserted between 1998 and 2001. This implant has been recorded as having a survival rate of 96% at ten years. However, in our series the survival rate was 75% at nine years. This was also significantly lower than that of subsequent consecutive series of PFC Sigma knee replacements performed by the same surgeon. No differences were found in the clinical and radiological parameters between the two groups. At revision the most striking finding was polyethylene wear. An independent analysis of the polyethylene components was therefore undertaken. Scanning electron microscopy revealed type 2 fusion defects in the ultra-high molecular weight polyethylene (UHMWPE), which indicated incomplete boundary fusion. Other abnormalities consistent with weak UHMWPE particle interface strength were present in both the explanted inserts and in unused inserts from the same period. We consider that these type 2 fusion defects are the cause of the early failure of the Kinemax implants. This may represent a manufacturing defect resulting in a form of programmed polyethylene failure

Retrieval studies of total hip replacements with highly cross-linked ultra-high-molecular-weight polyethylene liners have shown much less surface damage than with conventional ultra-high-molecular-weight polyethylene liners. A recent revision hip replacement for recurrent dislocation undertaken after only five months revealed a highly cross-linked polyethylene liner with a large area of visible delamination. In order to determine the cause of this unusual surface damage, we analysed the bearing surfaces of the cobalt-chromium femoral head and the acetabular liner with scanning electron microscopy, energy dispersive x-ray spectroscopy and optical profilometry. We concluded that the cobalt-chromium modular femoral head had scraped against the titanium acetabular shell during the course of the dislocations and had not only roughened the surface of the femoral head but also transferred deposits of titanium onto it. The largest deposits were 1.6 μm to 4.3 μm proud of the surrounding surface and could lead to increased stresses in the acetabular liner and therefore cause accelerated wear and damage. This case illustrates that dislocations can leave titanium deposits on cobalt-chromium femoral heads and that highly cross-linked ultra-high-molecular-weight polyethylene remains susceptible to surface damage

Nanometre-sized particles of ultra-high molecular weight polyethylene have been identified in the lubricants retrieved from hip simulators. Tissue samples were taken from seven failed Charnley total hip replacements, digested using strong alkali and analysed using high-resolution field emission gun-scanning electron microscopy to determine whether nanometre-sized particles of polyethylene debris were generated in vivo. A randomised method of analysis was used to quantify and characterise all the polyethylene particles isolated. We isolated nanometre-sized particles from the retrieved tissue samples. The smallest identified was 30 nm and the majority were in the 0.1 μm to 0.99 μm size range. Particles in the 1.0 μm to 9.99 μm size range represented the highest proportion of the wear volume of the tissue samples, with 35% to 98% of the total wear volume comprised of particles of this size. The number of nanometre-sized particles isolated from the tissues accounted for only a small proportion of the total wear volume. Further work is required to assess the biological response to nanometre-sized polyethylene particles

The aim of this study was to determine whether subchondral bone influences in situ chondrocyte survival. Bovine explants were cultured in serum-free media over seven days with subchondral bone excised from articular cartilage (group A), subchondral bone left attached to articular cartilage (group B), and subchondral bone excised but co-cultured with articular cartilage (group C). Using confocal laser scanning microscopy, fluorescent probes and biochemical assays, in situ chondrocyte viability and relevant biophysical parameters (cartilage thickness, cell density, culture medium composition) were quantified over time (2.5 hours vs seven days). There was a significant increase in chondrocyte death over seven days, primarily within the superficial zone, for group A, but not for groups B or C (p < 0.05). There was no significant difference in cartilage thickness or cell density between groups A, B and C (p > 0.05). Increases in the protein content of the culture media for groups B and C, but not for group A, suggested that the release of soluble factors from subchondral bone may have influenced chondrocyte survival. In conclusion, subchondral bone significantly influenced chondrocyte survival in articular cartilage during explant culture. The extrapolation of bone-cartilage interactions in vitro to the clinical situation must be made with caution, but the findings from these experiments suggest that future investigation into in vivo mechanisms of articular cartilage survival and degradation must consider the interactions of cartilage with subchondral bone

The belief that an intervertebral disc must degenerate before it can herniate has clinical and medicolegal significance, but lacks scientific validity. We hypothesised that tissue changes in herniated discs differ from those in discs that degenerate without herniation. Tissues were obtained at surgery from 21 herniated discs and 11 non-herniated discs of similar degeneration as assessed by the Pfirrmann grade. Thin sections were graded histologically, and certain features were quantified using immunofluorescence combined with confocal microscopy and image analysis. Herniated and degenerated tissues were compared separately for each tissue type: nucleus, inner annulus and outer annulus. Herniated tissues showed significantly greater proteoglycan loss (outer annulus), neovascularisation (annulus), innervation (annulus), cellularity/inflammation (annulus) and expression of matrix-degrading enzymes (inner annulus) than degenerated discs. No significant differences were seen in the nucleus tissue from herniated and degenerated discs. Degenerative changes start in the nucleus, so it seems unlikely that advanced degeneration caused herniation in 21 of these 32 discs. On the contrary, specific changes in the annulus can be interpreted as the consequences of herniation, when disruption allows local swelling, proteoglycan loss, and the ingrowth of blood vessels, nerves and inflammatory cells. In conclusion, it should not be assumed that degenerative changes always precede disc herniation. Cite this article: Bone Joint J 2013;95-B:1127–33

Four uncemented Symax hip stems were extracted at three weeks and nine, 13 and 32 months, respectively, for reasons other than loosening. The reasons for implant removal were infection in two cases, recurrent dislocation in one and acetabular fracture in one. They were analysed to assess the effect and behaviour of an electrochemically deposited, completely resorbable biomimetic BONIT-hydroxyapatite (HA) coating (proximal part) and a DOTIZE surface treatment (distal part) using qualitative histology, quantitative histomorphometry and scanning electron microscopy (SEM). Early and direct bone-implant bonding with signs of active remodelling of bone and the HA coating were demonstrated by histology and SEM. No loose BONIT-HA particles or delamination of the coating were observed, and there was no inflammation or fibrous interposition at the interface. Histomorphometry showed bone-implant contact varying between 26.5% at three weeks and 83.5% at 13 months at the HA-coated implant surface. The bone density in the area of investigation was between 24.6% at three weeks and 41.1% at 32 months. The DOTIZE surface treatment of the distal part of the stem completely prevented tissue and bone apposition in all cases, thereby optimising proximal stress transfer. The overall features of this implant, in terms of geometry and surface texture, suggest a mechanically stable design with a highly active biomimetic coating, resulting in rapid and extensive osseo-integration, exclusively in the metaphyseal part of the stem. Early remodelling of the HA coating does not seem to have a detrimental effect on short-term bone-implant coupling. There were no adverse effects identified from either the BONIT-HA coating or the DOTIZE surface treatment

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

We investigated the effect of progesterone on the nerve during lengthening of the limb in rats. The sciatic nerves of rats were elongated by leg lengthening for ten days at 3 mm per day. On alternate days between the day after the operation and nerve dissection, the progesterone-treated group received subcutaneous injections of 1 mg progesterone in sesame oil and the control group received oil only. On the fifth, tenth and 17th day, the sciatic nerves were excised at the midpoint of the femur and the mRNA expression level of myelin protein P0 was analysed by quantitative real time polymerase chain reaction. On day 52 nodal length was examined by electron microscopy, followed by an examination of the compound muscle action potential (C-MAP) amplitude and the motor conduction velocity (MCV) of the tibial nerve on days 17 and 52. The P0 (a major myelin glycoprotein) mRNA expression level in the progesterone-treated group increased by 46.6% and 38.7% on days five and ten, respectively. On day 52, the nodal length in the progesterone-treated group was smaller than that in the control group, and the MCV of the progesterone-treated group had been restored to normal. Progesterone might accelerate the restoration of demyelination caused by nerve elongation by activating myelin synthesis

Compartment syndrome, a devastating consequence of limb trauma, is characterised by severe tissue injury and microvascular perfusion deficits. We hypothesised that leucopenia might provide significant protection against microvascular dysfunction and preserve tissue viability. Using our clinically relevant rat model of compartment syndrome, microvascular perfusion and tissue injury were directly visualised by intravital video microscopy in leucopenic animals. We found that while the tissue perfusion was similar in both groups (38.8% (standard error of the mean (. sem). 7.1). , 36.4. % (. sem. 5.7), 32.0% (. sem. 1.7), and 30.5% (. sem. 5.35) continuously-perfused capillaries at 45, 90, 120 and 180 minutes compartment syndrome, respectively versus 39.2% (. sem. 8.6), 43.5% (. sem. 8.5). , . 36.6% (. sem. 1.4) and 50.8% (. sem. 4.8) at 45, 90, 120 and 180 minutes compartment syndrome, respectively in leucopenia), compartment syndrome-associated muscle injury was significantly decreased in leucopenic animals (7.0% (. sem. 2.0), 7.0%, (. sem. 1.0), 9.0% (. sem. 1.0) and 5.0% (. sem. 2.0) at 45, 90, 120 and 180 minutes of compartment syndrome, respectively in leucopenia group versus 18.0% (. sem. 4.0), 23.0% (. sem. 4.0), 32.0% (. sem. 7.0), and 20.0% (. sem. 5.0) at 45, 90, 120 and 180 minutes of compartment syndrome in control, p = 0.0005). This study demonstrates that the inflammatory process should be considered central to the understanding of the pathogenesis of cellular injury in compartment syndrome. Cite this article: Bone Joint J 2015;97-B:539–43

The collagen framework of articular cartilage is disposed, as in other connective tissues, to resist tension forces within the material. In this paper the fine structure of articular cartilage, as demonstrated by polarised light microscopy and electron microscopy, is related to the gross anatomy and to the naked eye changes of chondromalacia and fibrillation

Two Durasul highly crosslinked polyethylene liners were exchanged during revision surgery four and five years after implantation, respectively. The retrieved liners were evaluated macroscopically and surface analysis was performed using optical and electron microscopy. A sample of each liner was used to determine the oxidation of the material by Fourier transform infrared spectroscopy. Samples of the capsule were examined histologically. The annual wear rate was found to be 0.010 and 0.015 mm/year, respectively. Surface analysis showed very little loss of material caused by wear. Histological evaluation revealed a continuous neosynovial lining with single multinucleated foreign-body giant cells. Our findings showed no unexpected patterns of wear on the articulating surfaces up to five years after implantation and no obvious failure of material

Biochemical and histochemical studies have indicated that there is specific cellular activity in the region of the calcification front of articular cartilage implying that a regulation process takes place there. Using scanning and transmission electron microscopy and light microscopy to examine tissue sections of both undecalcified and decalcified articular cartilage in the region of the calcification front, we have looked at its morphology with particular reference to its cellular control. Our observations show that physiological calcification is an active process under cellular control and is related to the presence of extracellular membrane-bound matrix vesicles

1. The use of the Metals Research Macrotome for cutting 100 μ thick sections of fresh, unfixed specimens of arthritic human femoral heads and normal goat condyles is described. 2. A technique for isolating living cells from these slices by decalcification followed by enzymic digestion is reported. 3. The microscopic appearances of the fresh slices, the decalcified slices and the isolated cells as seen by incident or transmitted fluorescent lighting, by phase-contrast microscopy, by scanning electron microscopy and by histological and cytological techniques are illustrated. 4. These techniques might be applicable to the examination of biopsy specimens of pathological bone or to basic research on bone cells

The anterior cruciate ligament was replaced in rabbits, using implants of carbon or polyester filaments with known mechanical properties. The biocompatibility of the implants was assessed in detail using light microscopy, and scanning and transmission electron microscopy. Mechanical tests were made of stability, in comparison with normal joints and controls after excision of the ligament. Some carbon fibre implants broke down in vivo, allowing instability; the fragments caused chronic inflammation. Intact carbon implants did not induce the formation of neoligaments; they were covered by tissue, but there was no ingrowth. Polyester did not degrade mechanically and supported early collagenous ingrowth within the implant, even in the mid-joint space. It was concluded that there was no justification for the use of carbon fibres as anterior cruciate replacements; polyester appeared to be suitable

Four types of prosthetic replacement for the anterior cruciate ligament (carbon fibre, carbon fibre and Dacron composite, Dacron alone and bovine xenograft) were assessed at three, six and 12 months after implantation in the knees of New Zealand white rabbits. The synovium and both intra-articular and intra-osseous portions of the ligaments were examined macroscopically, by light microscopy and by scanning electron microscopy. All the knees showed mild synovitis, and there was no significant growth into the intra-articular part of any ligament. Carbon fibre and xenograft did not appear to be suitable materials in this animal model. The composite ligament showed short-term ingrowth of fibrous tissue only into the periphery of the sheath in its intra-osseous portion, whereas the Dacron ligament showed progressive fibrous tissue ingrowth with some bony incorporation of its outer fibres

Three normal digital flexor tendon sheaths and the corresponding tissue formed around five silicone rod tendon implants, two silicone rubber mammary prostheses and one polyethylene tubing implant have been examined by light microscopy and by transmission and scanning electron microscopy. No principal difference in morphology was found. The surface facing tendon or implant was almost invariably covered with an irregular layer of amorphous material and filaments; only occasionally were collagen fibrils or cells exposed. Beneath the surface there were abundant collagen fibrils and some cells; besides fibroblasts, cells rich in filaments and often with numerous glycogen granules, mitochondria and peripherally located vesicles were found. These cells were frequently surrounded by a thick layer of an amorphous matrix. The results indicate that the implants caused remarkably little tissue reaction

A longitudinal incision resembling a bucket-handle tear was made in the menisci of 8 rabbits, 6 dogs, 11 pigs and 12 sheep. In some of the animals of each species the cut was repaired by suturing, and in others it was not. Gross inspection, as well as examination by light and electron microscopy, showed that no healing had occurred after six months in the sutured or the unsutured wounds and that the meniscus was incapable of significant intrinsic repair. In a second experiment longitudinal, transverse and T-shaped cuts were made in the menisci of 12 sheep, and a flap of synovium was sutured into the wound. Three months later there was clear evidence of healing by the formation of cartilaginous tissue. Examination by light and electron microscopy showed that the newly formed repair tissue, possibly derived by metaplasia from the synovium, had a morphology intermediate between hyaline cartilage and fibrocartilage. Synovial implantation may therefore be considered as an alternative to meniscectomy in the management of the torn meniscus

1. Serial slices of articular cartilage obtained at necropsy from apparently normal femoral condyles of individuals between the ages of twenty-six and sixty were examined chemically, by electron microscopy and for permeability. 2. The most superficial layer was shown by chemical analysis and electron microscopy to have the highest collagen content, which fell sharply with distance from the articular surface. On the other hand the glycosaminoglycan content was very low in the superficial layers but increased with depth. This variation was found in all specimens tested but the absolute levels of collagen and of glycosaminoglycans were widely different. There was no correlation of chemical composition with age. 3. Collagen fibrils in the superficial layer were of much smaller diameter than in the deeper zones. 4. Hydraulic permeability was shown to depend more on glycosaminoglycan than on collagen content, although it varied inversely with both these factors. 5. The results obtained demonstrate clearly the close relation between the physical properties of cartilage and its chemical composition

In laboratory tests, the ultra-high molecular weight polyethylene used for the acetabular cups of Charnley hip prostheses has a very low wear rate against steel. In the body radiographic measurements indicate that the polyethylene wears more rapidly. In order to investigate this higher wear rate, the sockets of acetabular cups removed at post-mortem have been examined using optical and electron microscopy. It has been shown that a socket wears predominantly on its superior part and that this is a direct consequence of the orientation of the cup in the body and the direction of loading of the hip. In the worn region the femoral head in effect bores out a new socket for itself, a process which is visible with the naked eye after approximately eight years. Electron microscopy shows that the predominant wear mechanism is adhesion, but after about eight years the appearance of surface cracks suggests that surface fatigue is taking place in addition to this. Laboratory wear tests have shown that pure surface fatigue is not sufficient to account for the high clinical wear rate. Other deformation processes are suggested and discussed with regard to the higher clinical wear rate

Since the Oxford knee was first used unicompartmentally in 1982, a small number of bearings have fractured. Of 14 retrieved bearings, we examined ten samples with known durations in situ (four Phase 1, four Phase 2 and two Phase 3). Evidence of impingement and associated abnormally high wear (> 0.05 mm per year) as well as oxidation was observed in all bearings. In four samples the fracture was associated with the posterior radio-opaque wire. Fracture surfaces indicated fatigue failure, and scanning electron microscopy suggested that the crack initiated in the thinnest region. The estimated incidence of fracture was 3.20% for Phase 1, 0.74% for Phase 2, 0.35% for Phase 3, and 0% for Phase 3 without the posterior marker wire. The important aetiological factors for bearing fracture are impingement leading to high wear, oxidation, and the posterior marker wire. With improved surgical technique, impingement and high wear should be prevented and modern polyethylene may reduce the oxidation risk. A posterior marker wire is no longer used in the polyethylene meniscus. Therefore, the rate of fracture, which is now very low, should be reduced to a negligible level

Caveolae, specialised regions of the cell membrane which have been detected in a wide range of mammalian cells, have not been described in bone cells. They are plasmalemmal invaginations, 50 to 100 nm in size, characterised by the presence of the structural protein, caveolin, which exists as three subtypes. Caveolin-1 and caveolin-2 are expressed in a wide range of cell types whereas caveolin-3 is thought to be a muscle-specific subtype. There is little information on the precise function of caveolae, but it has been proposed that they play an important role in signal transduction. As the principal bone-producing cell, the osteoblast has been widely studied in an effort to understand the signalling pathways by which it responds to extracellular stimuli. Our aim in this study was to identify caveolae and their structural protein caveolin in normal human osteoblasts, and to determine which subtypes of caveolin were present. Confocal microscopy showed staining which was associated with the plasma membrane. Transmission electron microscopy revealed the presence of membrane invaginations of 50 to 100 nm, consistent with the appearance of caveolae. Finally, we isolated protein from these osteoblasts, and performed Western blotting using anti-caveolin primary antibodies. This revealed the presence of caveolin-1 and -2, while caveolin-3 was absent. The identification of these structures and their associated protein may provide a significant contribution to our further understanding of signal transduction pathways in osteoblasts

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

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.

Lesions within the articular cartilage layer of synovial joints do not heal spontaneously. Some repair cells may appear, but their failure to become established may be related to problems of adhesion to proteoglycan-rich surfaces. We therefore investigated whether controlled enzymatic degradation of surface proteoglycan molecules to a depth of about 1 μm, using chondroitinase ABC, would improve coverage by repair cells. We created superficial lesions (1.0 × 0.2 × 5 mm) in the articular cartilage of mature rabbit knees and treated the surfaces with 1 U/ml of chondroitinase ABC for four minutes. The defects were studied by histomorphometry and electron microscopy at one, three and six months. At one month, untreated lesions were covered to a mean extent of 28% by repair cells; this was enhanced to a mean of 53% after enzyme treatment. By three months, the mean coverage of both control and chondroitinase-ABC-treated defects had diminished dramatically to 0.2% and 13%, respectively, but at six months both untreated and treated lesions had a similar coverage of about 30%, not significantly different from that achieved in untreated knees at one month. These findings suggest that, with time, chondrocytes near the surface of the defect may compensate for the loss of proteoglycans produced by enzyme treatment, thereby restoring the inhibitory properties of the matrix as regards cell adhesion. This supposition was confirmed by electron microscopy. Our results have an important bearing on attempts made to induce healing responses by transplanting chondrogenic cells or by applying growth factors

1. The surface of mature adult human articular cartilage from the knee has been studied by electron microscopy in eleven patients ranging in age from thirty-seven to eighty-three years. The ultrastructural appearance varies from person to person and often from area to area in the same specimen. These variations range from an intact surface to one showing overt fibrillation visible with the light microscope. 2. In areas where the articular surface appears intact the underlying superficial matrix consists of closely packed collagen fibres with only a small amount of interfibrillary ground substance. The collagen fibres show a predominantly tangential orientation in this region of the cartilage. Osmophilic lipidic bodies are sometimes seen in the matrix very close to the joint surface. 3. The appearances under the electron microscope are altered in what is interpreted as an early ultrastructural change in the development of cartilage fibrillation. In the affected areas the collagen fibres show abnormally wide separation by an excessive amount of interfibrillary matrix. Collagen fibres become directly exposed to the joint cavity, and the surface can also show accumulations of finely granular material and sometimes tuft-like projections containing collagen fibres and fine fibrils. At a slightly later stage shallow clefts and steeply sloping curves are apparent at the surface. It is suggested that these various alterations precede the development of overt fibrillation visible under the light microscope. 4. Electron micrographs occasionally show small "blisters" at the articular surface. Electron microscopy has not given evidence of shedding of cells into the joint cavity from non-fibrillated areas of adult human articular cartilage. Cells can, however, sometimes become exposed at the surface in fibrillated areas

Aims

Rotational acetabular osteotomy (RAO) has been reported to be effective in improving symptoms and preventing osteoarthritis (OA) progression in patients with mild to severe develomental dysplasia of the hip (DDH). However, some patients develop secondary OA even when the preoperative joint space is normal; determining who will progress to OA is difficult. We evaluated whether the preoperative cartilage condition may predict OA progression following surgery using T2 mapping MRI.

The effect of zoledronic acid on bone ingrowth was examined in an animal model in which porous tantalum implants were placed bilaterally within the ulnae of seven dogs. Zoledronic acid in saline was administered via a single post-operative intravenous injection at a dose of 0.1 mg/kg. The ulnae were harvested six weeks after surgery. Undecalcified transverse histological sections of the implant-bone interfaces were imaged with backscattered scanning electron microscopy and the percentage of available pore space that was filled with new bone was calculated. The mean extent of bone ingrowth was 6.6% for the control implants and 12.2% for the zoledronic acid-treated implants, an absolute difference of 5.6% (95% confidence interval, 1.2 to 10.1) and a relative difference of 85% which was statistically significant. Individual islands of new bone formation within the implant pores were similar in number in both groups but were 69% larger in the zoledronic acid-treated group. The bisphosphonate zoledronic acid should be further investigated for use in accelerating or enhancing the biological fixation of implants to bone

Aims

The purpose of this study was to compare clinical results, long-term survival, and complication rates of stemless shoulder prosthesis with stemmed anatomical shoulder prostheses for treatment of osteoarthritis and to analyze radiological bone changes around the implants during follow-up.

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.

Aims

The aims of this study were to evaluate wear on the surface of cobalt-chromium (CoCr) femoral components used in total knee arthroplasty (TKA) and compare the wear of these components with that of ceramic femoral components.

Aims

The aim of this study was to determine the extent to which patient demographics, clinical presentation, and blood parameters vary in Kingella kingae septic arthritis when compared with those of other organisms, and whether this difference needs to be considered when assessing children in whom a diagnosis of septic arthritis is suspected.

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.

Ketamine has been used in combination with a variety of other agents for intra-articular analgesia, with promising results. However, although it has been shown to be toxic to various types of cell, there is no available information on the effects of ketamine on chondrocytes. We conducted a prospective randomised controlled study to evaluate the effects of ketamine on cultured chondrocytes isolated from rat articular cartilage. The cultured cells were treated with 0.125 mM, 0.250 mM, 0.5 mM, 1 mM and 2 mM of ketamine respectively for 6 h, 24 hours and 48 hours, and compared with controls. Changes of apoptosis were evaluated using fluorescence microscopy with a 490 nm excitation wavelength. Apoptosis and eventual necrosis were seen at each concentration. The percentage viability of the cells was inversely proportional to both the duration and dose of treatment (p = 0.002 and p = 0.009). Doses of 0.5 mM, 1 mM and 2mM were absolutely toxic. We concluded that in the absence of solid data to support the efficacy of intra-articular ketamine for the control of pain, and the toxic effects of ketamine on cultured chondrocytes shown by this study, intra-articular ketamine, either alone or in combination with other agents, should not be used to control pain. Cite this article: Bone Joint J 2014; 96-B:989–94

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

To investigate metallosis in patients with magnetically controlled growing rods (MCGRs) and characterize the metal particle profile of the tissues surrounding the rod.

We obtained samples of spinal accessory nerve from patients undergoing radical surgery for tumours or nerve grafting in the neck. These were analysed by light and electron microscopy for the type of fibre. All contained fibres consistent with non-proprioceptive sensory function including pain

We present the case of a 63-year-old woman who sustained an acrylic cement burn of the sciatic nerve at hip replacement. She was treated by resection of the damaged segment and grafting. Electron microscopy showed that the nerve was nearly normal 1 cm from the cement margin indicating that this is a safe level for resection

1. The orientation of collagen fibres of the menisci of the knee has been demonstrated by polarised light microscopy. 2. As might be supposed from its fibre structure, the ultimate tensile strength of the meniscal tissue is dependent upon the axis of loading. 3. The tensile strength of the meniscus is similar to that of articular cartilage

We studied factors contributing to the initiation of fracture and failure of a zirconia ceramic femoral head. The materials retrieved during a revision total hip replacement were submitted to either visual, stereomicroscopic and scanning electron microscopy (SEM) or SEM and energy-dispersive x-ray analysis. X-ray diffraction was performed in order to investigate the extent of tetragonal to monoclinic phase transition. Histological examination was performed on the periprosthetic tissues. The results showed that failure was due to the propagation during clinical use of defects which may have been introduced into the material during the processing of the ceramic, rather than those intrinsic to zirconia. The literature relating to previous failures of zirconia components is reviewed

Teratomas in the spinal cord are rare. We report a case in a 54-year-old man. CT scans revealed tumours of different densities within the spinal canal; this heterogeneity may help to differentiate teratoma from other spinal cord tumours. After resection of the tumours under microscopy, the result was excellent. Histological examination showed a variety of tissues, including elements of all three germinal layers

An extremely strong mechanical bond between cement and bone was observed in three patients with cemented hip protheses who underwent revision operations. The nature of the bone--cement attachment was studied by electron microscopy. The tissue at the interface was found to be made up of viable bone alternating with areas of soft tissue containing macrophages. The important qualitative differences between this reaction and the reaction seen around inert materials such as titanium are discussed

Results are given of a study of four cases of osteogenesis imperfecta using biophysical methods comprising microradiography, microscopy using polarised light, and x-ray diffraction. Rebuilding of bone tissue was infrequent in the material studied and has been shown to occur in an abnormal manner. The mineralisation of the bone is more uniform than is found in normal bone. The collagen has an abnormal organisation and is sparse. The ultrastructure of bone salts and their orientation are as in normal bone

1. A method is described for the in vivo and in vitro study of osteogenesis by implanting a modified transparent chamber in half lop-eared rabbits (as originated by Sandison 1928). This method allows the daily observation and photography of the developing bone and the study of its intimate connection with the vascularity of the area. 2. The osteogenetic potential of a variety of substances can also be investigated by this method. The tissue in the chamber can easily be prepared for its final examination by optical and electron microscopy and by other laboratory techniques

Specimens of tissue from haemophilic synovium and articular cartilage were collected from 39 patients during reconstructive surgery. They were studied by histochemistry, electron microscopy and microprobe analysis. The detailed findings are presented and discussed. It is suggested that haemophilic arthropathy is the result of a number of mechanisms affecting the synovial lining which becomes progressively fibrotic and the hyaline cartilage which disintegrates and is eventually lost. Mechanical and chemical processes cause degeneration of cells but enzymatic processes appear to be primarily responsible for the degradation of the matrix of the articular cartilage

We obtained specimens of growth-plate cartilage from four patients with osteogenesis imperfecta. Light microscopy showed structural changes in the tissue and morphological changes in chondrocytes and matrix, particularly in the hypertrophic zone. There were changes in the process of calcification in the primary mineralisation zone of the cartilage. We also found histochemical changes in the matrix glycosaminoglycans (GAGs) in the zones where physiological mineralisation was disturbed and where the trabeculae were interrupted and poorly mineralised. In addition to the known molecular defects in collagen, changes in GAGs and non-collagenous proteins are important factors in the pathogenesis of the disease

Three madreporic prostheses in two patients were examined to evaluate resorption and formation of the surrounding bone tissue. All three prostheses were firmly fixed and had no clinical or radiographic signs of loosening. Transverse sections were examined by scanning electron microscopy at 40 days, 11 months and 2.5 years after implantation. The findings suggest that adaptive bone remodelling varies along the length of the stem; that bone resorption and formation are related to the time after implant; and that new bone formation (woven bone) can be found very close to the madreporic surface

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.

We studied the most superficial layer of macroscopically normal articular cartilage obtained from human femoral heads, using polarising microscopy and SEM. The most superficial layer, 4 to 8 microns thick, was acellular consisting of collagen fibrils. This layer could be peeled away as a thin film, with no broken collagen fibrils on its inferior surface or on the surface of subjacent cartilage layers. The orientation and diameter of collagen fibrils were different on these two surfaces. Our findings suggest that the most superficial layer is an independent one which is only loosely connected to the fibrous structure in the layer deep to it

We cultured human osteoblasts from trabecular bone explants and confirmed their phenotype by alkaline phosphatase assay, increased cyclic adenosine monophosphate production in response to prostaglandin E2 and radiographic micro-analysis of nodules of calcification. The osteoblasts were seeded on to demineralised human bone fragments and examined at ten-day intervals over a 50-day period by scanning electron microscopy. During this time the bank bone became progressively repopulated by the cultured osteoblasts. This system may offer a means of graft enhancement in elective orthopaedic and maxillofacial surgery by delivery of cultured autologous human osteoblasts to bone defects

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

Full thickness samples of articular cartilage were removed from areas of chondromalacia on the medial and "odd" facets of the patellae of 21 adults and examined by histology, autoradiography and electron microscopy. Surface fibrillation, loss of superficial matrix staining and reduced 35SO4 labelling was seen, with little change in the deep zone. Ten cases showed "fibrous metaplasia" of the superficial cartilage with definite evidence of cell division and apparent smoothing of the surface. Scattered chondrocyte replication appeared to occur in the surrounding intact cartilage. The findings suggest that early lesions in chondromalacia patellae may heal either by cartilage or fibrous metaplasia and that this may account for the resolution of clinical symptoms

1. Human articular cartilage from normal femoral heads and from cases of osteoarthrosis in subjects of various ages has been examined histologically and by electron microscopy. 2. In specimens from middle-aged and old subjects, peculiar "matrix-streaks" have been observed in the deep zone of the pressure areas as oblique bands extending from the pericellubar halos into the adjacent matrix. 3. Ultrastructurally the streaks are correlated with an undulating pattern of the radially oriented collagen fibres. 4. The streaks are considered to result from a focal lack of acid mucopolysaccharide and from natural forces on the articular cartilage. Their appearance is assumed to be an early sign of cartilage disintegration associated with ageing

Four cases are described of solitary spinal neurofibroma, a rare tumour of the spinal cord or nerve roots. Computerised tomography provided an accurate topographical definition of the tumour. Magnetic resonance imaging showed an increased T2-weighted signal and multiple areas of decreased T1- and T2-weighted signals centrally. The MR signals matched the histological examination which showed hyperplastic interfascicular connective tissue, pleomorphic cells, and tightly packed nerve fibres compressed by the surrounding loose connective tissue. Electron microscopy showed three types of cell: Schwann cells, fibroblast-like cells, and mast cells. The histological findings suggests that solitary spinal neurofibroma is a distinct pathological entity which could be diagnosed preoperatively from the MR images

Tissue engineering is an increasingly popular method of addressing pathological disorders of cartilage. Recent studies have demonstrated its clinical efficacy, but there is little information on the structural organisation and biochemical composition of the repair tissue and its relation to the adjacent normal tissue. We therefore analysed by polarised light microscopy and immunohistochemistry biopsies of repair tissue which had been taken 12 months after implantation of autologous chondrocytes in two patients with defects of articular cartilage. Our findings showed zonal heterogeneity throughout the repair tissue. The deeper zone resembled hyaline-like articular cartilage whereas the upper zone was more fibrocartilaginous. The results indicate that within 12 months autologous chondrocyte implantation successfully produces replacement cartilage tissue, a major part of which resembles normal hyaline cartilage

We have studied the formation of collagen fibrils in ‘activated fibroblasts’ of tendo Achillis of rabbits. The tendon was in the process of regeneration after experimental partial tenotomy. Samples were taken from the peri-incisional region and analysed by transmission electron microscopy. Ultrastructural examination showed the presence of a ‘fine dense granular substance’ inside the rough endoplasmic reticulum and procollagen filaments. These come together to form collagen fibrils in the dilated vacuoles of the rough endoplasmic reticulum. The possible intra- and extracellular origin of collagen fibrils is suggested. Within the cell biosynthesis of collagen fibrils take place with the formation of collagen substance which gives rise to procollagen filaments. These make contact in parallel apposition to produce striated ‘spindle-shaped bodies’ which elongate by the longitudinal attachment of more procollagen filaments and form intracellular nascent collagen fibrils

We investigated the pathogenesis of soft-tissue contracture in club foot, using immunohistochemistry to study 41 biopsy specimens and 12 normal deltoid ligaments from cadavers. Five biopsy specimens were studied by electron microscopy (EM) to determine the presence of myofibroblasts. All 41 specimens of club foot stained positively for vimentin as against only one of the 12 control specimens. By contrast, there was no difference in staining for desmin or α-smooth muscle actin. EM showed some variability in the appearance of ligamentous cells. Most contained bundles of microfilaments in the cytoplasm and many had abundant pinocytotic vesicles, but no basal lamina or plasmalemmal attachment plaques. Cells of the medial ligamentous tissue in patients with club foot contain vimentin and others have myofibroblastic characteristics. Both features may contribute to recurrence after soft-tissue release

We reviewed 35 of 38 consecutive patients who had operative treatment for medial epicondylitis of the elbow after the failure of conservative management. Their mean age was 43 years and mean follow-up was 85 months. At operation residual tears with incomplete healing were consistently found in the flexor origin at the medial epicondyle and microscopy showed reactive fibrous connective tissue with varying degrees of inflammation. The mean subjective estimate of elbow function was improved from 38% to 98% of normal, while isokinetic and grip strength testing in 16 patients showed no significant difference from the unoperated elbow. Results were excellent in 25 cases, good in nine and fair in one; 86% of the patients had no limitation in the use of the elbow

In 20 skeletally mature female merino sheep, divided into four groups, we performed total medial meniscectomy, removal of the middle third of the patellar tendon, and tenotomy of the calcaneal tendon of the right hind leg. Group I (control) had no additional procedures. In the other three groups the medial meniscus was replaced by the middle third of the patellar tendon from the ipsilateral knee. The animals were killed at three (group II), six (group III), or 12 months (group IV) and the tendon-meniscus examined macroscopically, by light and scanning electron microscopy, and biomechanically. Remodelling of the tissue had taken place by 12 months but the failure stress and tensile modulus for the tendon-meniscus were lower than for the normal meniscus. Our evidence suggests that, in sheep, replacement of a meniscus by a tendon autograft may decrease the severity of the degenerative changes that occur after meniscectomy

The three-dimensional architecture of bovine articular cartilage collagen and its relationship to split lines has been studied with scanning electron microscopy. In the middle and superficial zones, collagen was organised in a layered or leaf-like manner. The orientation was vertical in the intermediate zone, curving to become horizontal and parallel to the articular surface in the superficial zone. Each leaf consisted of a fine network of collagen fibrils. Adjacent leaves merged or were closely linked by bridging fibrils and were arranged according to the split-line pattern. The surface layer (lamina splendens) was morphologically distinct. Although ordered, the overall collagen structure was different in each plane (anisotropic) a property described in previous morphological and biophysical studies. As all components of the articular cartilage matrix interact closely, the three-dimensional organisation of collagen is important when considering cartilage function and the processes of cartilage growth, injury and repair

To study the anatomy of subarticular bone and cartilage, fresh specimens of cartilage on bone from the human shoulder, hip and knee were treated with bleach or papain, or were fixed and decalcified. All were compared using scanning electron microscopy. Papain digestion selectively removed cartilage to the tidemark. The tidemark contour was highly variable; irregularities were indirectly related to degenerative lesions and were most prominent in peripheral non-weight-bearing areas of joints with central fibrillation. Decalcification exposed the interface between the bone and calcified cartilage. Collagen fibrils in articular cartilage did not interdigitate with those of bone. The subchondral bone was appositional, avascular, smooth and very thin in most areas of human joints. Perforations through subchondral bone or calcified cartilage were rare. Bleach maceration destroyed important details

Quantitative polarised light microscopy was applied to sections of unfixed, undecalcified bone taken at operation from patients with two types of proximal femoral fracture, subcapital and trochanteric. Specimens were also taken from the equivalent sites in otherwise normal subjects at autopsy, and from various other sites of traumatic fractures; these two latter groups acted as controls. Analysis of the 57 specimens disclosed changes in the nature of the bone at the site of subcapital fractures, namely the presence of relatively large crystals of hydroxyapatite and a change in the molecular orientation, but not total content, of the acidic proteoglycans of the bone matrix. Our results have confirmed and extended the findings of others on subcapital fractures, and have also shown very similar changes in the trochanteric fractures. It thus appears that the bony changes in the two types of proximal femoral fracture are not as different as has been suggested

The anatomy of the autonomic sympathetic vasomotor nerve supply of bone was studied in rabbits by methods of histochemistry, and fluorescent and electron microscopy. Our observations show that the intraosseous vessels are richly supplied by adrenergic nerves. The large primary nerves are located on or about the surface of the vessel; the medium sized secondary nerves spiral around the long axis of vessels lying more deeply in the tunica adventitia; and the fine tertiary nerves form a rich plexus at the outer area of the tunica media. The tertiary nerves have various structures which probably contain neurotransmitter substance--that is, noradrenaline--and function as neuro-vasomuscular synapses. The sympathetic nerve supply of bone originates from the appropriate ganglion, and in the case of the tibial diaphysis it descends through the sciatic nerve and thereafter mainly through the medial popliteal nerve and enters the bone alongside the nutrient artery

In developmental dysplasia of the hip, a deficient acetabulum may be augmented by placing local autogenous iliac osseous graft, or the ilium itself, over the head of the femur with the expectation that the added bone will function as a bearing surface. We analysed this bone obtained en bloc during subsequent surgery which was performed for degenerative osteoarthritis in three patients at 6, 25 and 30 years after the initial augmentation procedure. In each patient, the augmentation comprised of red cancellous bone covered on its articulating surface by a distinct layer of white tissue. Microscopy of this tissue showed parallel rows of spindle-shaped cells lying between linearly arranged collagen bundles typical of joint capsule. Biochemical analysis showed type I collagen, the principal collagen of joint capsule and bone, with no significant quantity of type II collagen, the principal collagen of cartilage. While the added bone produced by acetabular augmentation was durable, histological and biochemical analyses suggested that it had not undergone cartilage metaplasia. The augmented acetabulum articulates with the head of the femur by means of an interposed hip joint capsule

The clinical features, investigation, treatment and outcome of two adults with fibrogenesis imperfecta ossium are described. In this rare acquired disorder of bone, normal lamellar collagen is replaced by structurally unsound collagen-deficient tissue, which leads to extreme bone fragility and ununited fractures. Transmission microscopy and SEM showed striking ultrastructural changes in bone structure and mineralisation. Both patients had monoclonal IgG paraproteins in the plasma and one excreted monoclonal lambda light chains in the urine. No abnormal plasma cells were found in the bone marrow and there was no evidence of amyloid deposition in the tissues. In both patients initial treatment with 1 alpha-hydroxycholecalciferol appeared to be ineffective, but in one, repeated courses of melphalan and corticosteroids over three years together with 1 alpha-hydroxycholecalciferol produced striking clinical and histological improvement. The findings in these and other patients strongly suggest that paraproteinaemia is an integral feature of fibrogenesis imperfecta ossium, and this needs further investigation

Fifty-four cobalt-chrome alloy femoral heads were retrieved at revision surgery or at post-mortem; 23 came from uncemented, eight from hybrid and 23 from cemented hip arthroplasties. The uncemented and hybrid implants had porous coating, metal backing and modular femoral heads; with one exception none of the cemented implants had any of these. Twenty-five of the 31 heads from uncemented and hybrid arthroplasties, and 11 of the 23 heads from cemented arthroplasties showed surface damage involving more than 25% of the surface. Scanning electron microscopy revealed multidirectional fine scratches 1 micron to 10 microns in depth and width which appeared to have been made by fine, hard particles. There was a higher rate of such damage in the uncemented and hybrid arthroplasties than in the cemented implants, suggesting that the abrasive particles were mainly released from the metal, rather than from the cement or polyethylene components of the implants

Aims

HIV predisposes patients to opportunistic infections. However, with the establishment of Highly Active Anti-Retroviral Therapy (HAART), patients’ CD4 counts are maintained, as is a near normal life expectancy. This study aimed to establish the impact of HIV on the bacteriology of spondylodiscitis in a region in which tuberculosis (TB) is endemic, and to identify factors that might distinguish between them.

Free patellar tendon grafts used for the intra-articular replacement of ruptured anterior cruciate ligaments (ACL) lack perfusion at the time of implantation. The central core of the graft undergoes a process of ischaemic necrosis which may result in failure. Early reperfusion of the graft may diminish the extent of this process. We assessed the role of peritendinous connective tissue in the revascularisation of the patellar tendon graft from the day of implantation up to 24 days in a murine model using intravital microscopy. The peritendinous connective-tissue envelope of the graft was either completely removed, partially removed or not stripped before implantation into dorsal skinfold chambers of recipient mice. Initial revascularisation of the grafts with preserved peritendinous connective tissues began after two days. The process was delayed by five to six times in completely stripped patellar tendons (p < 0.05). Only grafts with preserved connective tissues showed high viability whereas those which were completely stripped appeared to be subvital. The presence of peritendinous connective tissues accelerates the revascularisation of free patellar tendon grafts

We report the long-term radiological results of 58 total hip arthroplasties (THA) using the Charnley offset-bore acetabular socket. Wear was measured at four sites and radiolucent lines and possible migration were recorded. Four cups were retrieved at revision and were examined using light microscopy, SEM and X-ray microanalysis. At a mean follow-up of seven years the mean wear in the DeLee and Charnley zone I was 0.4 mm and in zone II 0.26 mm. The wear rate was 0.06 and 0.04 mm/year, respectively. Progression of radiolucent lines was seen in five cases (8.6%). Three sockets (5.2%) were revised because of aseptic migration at a mean follow-up of 9.8 years and one socket for infection at two years. The offset-bore acetabular cup had excellent wear behaviour and a low migration and revision rate. We recommend that it should be considered in THA since the use of small cups is increasing, particularly in revision cases

Abundant implant-derived biomaterial wear particles are generated in aseptic loosening and are deposited in periprosthetic tissues in which they are phagocytosed by mononuclear and multinucleated macrophage-like cells. It has been stated that the multinucleated cells which contain wear particles are not bone-resorbing osteoclasts. To investigate the validity of this claim we isolated human osteoclasts from giant-cell tumours of bone and rat osteoclasts from long bones. These were cultured on glass coverslips and on cortical bone slices in the presence of particles of latex, PMMA and titanium. Osteoclast phagocytosis of these particle types was shown by light microscopy, energy-dispersive X-ray analysis and SEM. Giant cells containing phagocytosed particles were seen to be associated with the formation of resorption lacunae. Osteoclasts containing particles were also calcitonin-receptor-positive and showed an inhibitory response to calcitonin. Our findings demonstrate that osteoclasts are capable of phagocytosing particles of a wide range of size, including particles of polymeric and metallic bio-materials found in periprosthetic tissues, and that after particle phagocytosis, they remain fully functional, hormone-responsive, bone-resorbing cells

We designed an in vivo study to determine if the superimposition of a microtexture on the surface of sintered titanium beads affected the extent of bone ingrowth. Cylindrical titanium intramedullary implants were coated with titanium beads to form a porous finish using commercial sintering techniques. A control group of implants was left in the as-sintered condition. The test group was etched in a boiling acidic solution to create an irregular surface over the entire porous coating. Six experimental dogs underwent simultaneous bilateral femoral intramedullary implantation of a control implant and an acid etched implant. At 12 weeks, the implants were harvested in situ and the femora processed for undecalcified, histological examination. Eight transverse serial sections for each implant were analysed by backscattered electron microscopy and the extent of bone ingrowth was quantified by computer-aided image analysis. The extent of bone ingrowth into the control implants was 15.8% while the extent of bone ingrowth into the etched implants was 25.3%, a difference of 60% that was statistically significant. These results are consistent with other research that documents the positive effect of microtextured surfaces on bone formation at an implant surface. The acid etching process developed for this study represents a simple method for enhancing the potential of commonly available porous coatings for biological fixation

We compared the effects of continuous passive motion with those of intermittent active motion on the results of the resurfacing with autogenous periosteal grafts of full-thickness defects on the articular surface of rabbit patellae. Of 45 rabbits with defects, 30 received grafts. Fifteen of these had continuous passive motion for two weeks and intermittent active motion for four weeks; the other 15 had intermittent active motion for six weeks. In 15 the defects were not grafted (control group) and they had intermittent active motion for six weeks. Ten more rabbits had a sham operation. Six weeks after surgery, the results were assessed by the gross appearance, histology, histochemistry, immunohistochemistry and electron microscopy. By all assessments the quality of neochondrogenesis produced by periosteal grafts was superior to that in ungrafted defects (p less than 0.05) and the results in continuous passive motion treated animals were superior to those in intermittent active motion treated animals (p less than 0.05). The periosteal grafts produced hyaline cartilage containing type II collagen but the organisation of its fibres was irregular

Wear products of metal implants are known to induce biological events which may have profound consequences for the microcirculation of skeletal muscle. Using the skinfold chamber model and intravital microscopy we assessed microcirculatory parameters in skeletal muscle after confrontation with titanium and stainless-steel wear debris, comparing the results with those of bulk materials. Implantation of stainless-steel bulk and debris led to a distinct activation of leukocytes combined with a disruption of the microvascular endothelial integrity and massive leukocyte extravasation. While animals with bulk stainless steel showed a tendency to recuperation, stainless-steel wear debris induced such severe inflammation and massive oedema that the microcirculation broke down within 24 hours after implantation. Titanium bulk caused only a transient increase in leukocyte-endothelial cell interaction within the first 120 minutes and no significant change in macromolecular leakage, leukocyte extravasation or venular diameter. Titanium wear debris produced a markedly lower inflammatory reaction than stainless-steel bulk, indicating that a general benefit of bulk versus debris could not be claimed. Depending on its constituents, wear debris is capable of eliciting acute inflammation which may result in endothelial damage and subsequent failure of microperfusion. Our results indicate that not only the bulk properties of orthopaedic implants but also the microcirculatory implications of inevitable wear debris play a pivotal role in determining the biocompatibility of an implant

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

The aim of this study was to try to elucidate the increased susceptibility of the neck of femur to fracture. Quantitative polarised light microscopy has been applied to fresh, undecalcified sections of samples of bone taken from the site of fracture, in specimens taken at operation from patients with fractures of the femoral neck or osteoarthritic femoral heads or from the equivalent site from otherwise normal subjects at necropsy. In all 21 specimens of fractured necks of femur, but in none of the other specimens, relatively large crystals (up to 2.5 X 0.5 micrometres) were found close to the site of fracture; the properties of these crystals were compatible with their being apatite. Measurement of the natural birefringence of the collagen showed no difference in the orientation of the collagen in all three types of specimen. However, the orientation of acidic glycosaminoglycans, measured by the birefringence of alcian blue bound to these moieties, was 45 per cent lower in the specimens from fractured necks of femur than in the other specimens, even though the total content of acidic glycosaminoglycans was unchanged. Although the decreased orientation was most marked close to the site of fracture, it was still apparent 15 millimetres from that site. These changes were unlikely to be simply the sequelae of fracture since they were not found in traumatic fractures of other bones. Thus it is conceivable that changes in the orientation of the ground substance allow formation of relatively large crystals of apatite and that such crystals, in the microcrystalline mass of apatite, are the cause of the increased fragility of such bones

1. Four cases of osteomalacia secondary to vitamin D deficiency have been investigated histologically and with the electron microscope. 2. Three main types of cells were found along the osteoid tissue. Cells of Group 1 are like normal osteoblasts, except that their cytoplasm has an ordered granular endoplasmic reticulum, without enlarged cysternae. Moreover, it contains isolated rosettes of glycogen. Cells of Group 2 are like young progenitor cells. There are almost no rough cysternae in the cytoplasm. This contains clusters of glycogen, isolated ribosomes and many mitochondria. Cells of Group 3 are structurally like "resting" flat osteoblasts in normal bone. 3. The paper discusses how the presence of the three groups may be related to vitamin D deficiency or secondary hyperparathyroidism. 4. Malacic osteoid tissue consists of apparently normal collagen fibrils. Both optical and electron microscopy show that this tissue can calcify. But calcification stops at an early stage, or proceeds much more slowly than normal. So large areas ofosteoid tissue are left uncalcified. 5. Calcium salts are laid down either as needle-shaped crystals exactly like those in normal bone, or else abnormally. Where abnormal they either appear in a finely granular, almost amorphous form, or else acquire a characteristic star-like crystalline structure. 6. Where calcification takes place bundles of laterally aggregated collagen fibrils are found

1 . Normal and diseased bone was obtained by biopsy from five patients suffering from Paget's disease. The tissue was studied by histology, microradiography and quantitative fluorescence microscopy using tetracycline markers. Study of the morphological changes showed that two of the biopsies could be regarded as normal, while one was osteoporotic; two biopsy specimens were in the porotic phase of Paget's disease and the remaining five were in the sclerotic phase. 2. The tetracycline markers were used to measure the linear rate at which bone was deposited on individual surfaces (appositional growth rate) in µ per day and the percentage volume of new bone added to the total volume of bone per day (bone formation rate). The values obtained for appositional growth rate in all the biopsies were of the order of 1 µ per day, but slightly higher values were obtained in the diseased tissue of each individual. The bone formation rate in normal bone from the proximal femur was about 0·04 per cent per day, about 0·13 per cent per day in the porotic phase, and about 0·4 per cent per day in the sclerotic phase of Paget's disease. 3. Although these values must be accepted with some reservation, there seems to be no doubt that there is an upper limit of about 1 µ per day to the rate of deposition of bone on an individual bone surface; this suggests that in Paget's disease the osteoblast behaves as a normal cell

We report a prospective study of the liner-metal interfaces of modular uncemented acetabular components as sources of debris. We collected the pseudomembrane from the screw-cup junction and the empty screw holes of the metal backing of 19 acetabula after an average implantation of 22 months. Associated osteolytic lesions were separately collected in two cases. The back surfaces of the liners and the screws were examined for damage, and some liners were scanned by electron microscopy. The tissues were studied histologically and by atomic absorption spectrophotometry to measure titanium content. The pseudomembrane from the screw-cup junction contained polyethylene debris in seven specimens and metal debris in ten. The material from empty screw holes was necrotic tissue or dense fibroconnective tissue with a proliferative histiocytic infiltrate and foreign-body giant-cell reaction. It contained polyethylene debris in 14 cases and metal in five. The two acetabular osteolytic lesions also showed a foreign-body giant-cell reaction to particulate debris. The average titanium levels in pseudomembranes from the screw-cup junction and the empty screw holes were 959 micrograms/g (48 to 11,900) and 74 micrograms/g (0.72 to 331) respectively. The tissue from the two lytic lesions showed average titanium levels of 139 and 147 micrograms/g respectively. The back surfaces of the PE liners showed surface deformation, burnishing, and embedded metal debris. All 30 retrieved screws demonstrated fretting at the base of the head and on the proximal shaft. Non-articular modular junctions create new interfaces for the generation of particulate debris, which may cause granulomatous reaction

Cytological analysis of material aspirated from the effusion which occasionally develops around a polyglycolic acid (PGA) osteosynthesis implant showed a predominance of inflammatory monocytes and in particular lymphocytes. In order to discover whether PGA implants are immunologically inert, density gradient-isolated peripheral blood mononuclear cells were cultured in 0.2 ml of 10% delta FCS-RPMI 1640 culture medium supplemented with 10 mg PGA. Phytohaemagglutinin (PHA) lectin, a purified protein derivate of tuberculin (PPD) antigen and culture medium alone were used as positive and negative controls. We studied lymphocyte activation kinetics on days 0, 1, 3 and 5. Major histocompatibility complex locus II antigen (MHC locus II antigen) and interleukin-2 receptor (IL-2R) expression were analysed using the avidin-biotin-peroxidase complex (ABC) method and lymphocyte DNA synthesis by using 3H-thymidine incorporation and beta-scintillation counting. Especially on culture days 0 and 1, lymphocytes and monocytes were seen by light microscopy to be attached to PGA particles. However, our results show no PGA-induced lymphocyte DNA synthesis, but PGA-induced MHC locus II antigen and IL-2R activation marker expression was seen, greater than in negative controls, but less than that seen in PPD antigen driven lymphocyte response. This suggests that PGA is an immunologically inert implant material, but it does seem to induce inflammatory mononuclear cell migration and adhesion, leading to a slight non-specific lymphocyte activation. This activation is lower than that seen in mitogen and antigen-driven lymphocyte responses

A major pathway of closed soft-tissue injury is failure of microvascular perfusion combined with a persistently enhanced inflammatory response. We therefore tested the hypothesis that hypertonic hydroxyethyl starch (HS/HES) effectively restores microcirculation and reduces leukocyte adherence after closed soft-tissue injury. We induced closed soft-tissue injury in the hindlimbs of 14 male isoflurane-anaesthetised rats. Seven traumatised animals received 7.5% sodium chloride-6% HS/HES and seven isovolaemic 0.9% saline (NS). Six non-injured animals did not receive any additional fluid and acted as a control group. The microcirculation of the extensor digitorum longus muscle (EDL) was quantitatively analysed two hours after trauma using intravital microscopy and laser Doppler flowmetry, i.e. erythrocyte flux. Oedema was assessed by the wet-to-dry-weight ratio of the EDL. In NS-treated animals closed soft-tissue injury resulted in massive reduction of functional capillary density (FCD) and a marked increase in microvascular permeability and leukocyte-endothelial cell interaction as compared with the control group. By contrast, HS/HES was effective in restoring the FCD to 94% of values found in the control group. In addition, leukocyte rolling decreased almost to control levels and leukocyte adherence was found to be reduced by ~50%. Erythrocyte flux in NS-treated animals decreased to 90 ± 8% (mean . sem. ), whereas values in the HS/HES group significantly increased to 137 ± 3% compared with the baseline flux. Oedema in the HS/HES group (1.06 ± 0.02) was significantly decreased compared with the NS-group (1.12 ± 0.01). HS/HES effectively restores nutritive perfusion, decreases leukocyte adherence, improves endothelial integrity and attenuates oedema, thereby restricting tissue damage evolving secondary to closed soft-tissue injury. It appears to be an effective intervention, supporting nutritional blood flow by reducing trauma-induced microvascular dysfunction

Our aim was to examine the potential of autologous perichondral tissue to form a meniscal replacement. In 18 mature sheep we performed a complete medial meniscectomy. The animals were then divided into two groups: 12 had a meniscal replacement using strips of autologous perichondral tissue explanted from the lower rib (group G) and six (group C) served as a control group without a meniscal replacement. In all animals restriction from weight-bearing was achieved by means of transection and partial resection of tendo Achillis. Six animals (four from group G and two from group C) were each killed at 3, 6 and 12 months. The grafts and the underlying articular cartilage were removed and studied by gross macroscopic examination, light microscopy, SEM, polarised light examination, and by biomechanical tests. In all the transplanted animals a new perichondral meniscus developed. After three months the transplants resembled normal menisci in size and thickness, while in the control animals only small rims of spontaneously grown tissue were seen. Microscopically, the perichondral menisci showed a normal orientation of collagen fibres and normal cellular characteristics, but in the central region, areas of calcification disturbed the regular tissue differentiation. Healing tissue in control animals lacked the normal fibre orientation and cellularity. SEM of perichondral menisci showed surface characteristics similar to those of normal sheep menisci without fissures and lacerations; the control specimens had these defects. The femoral and tibial cartilage in contact with the new menisci had normal surface characteristics apart from one animal with slight surface irregularities. Control animals showed superficial lesions after three months which increased at six to 12 months postoperatively. Microangiography of the newly grown tissue demonstrated a less intense vascularisation after three months when compared with normal menisci. The failure stress and tensile modulus of perichondral menisci were significantly lower than those of normal contralateral menisci, and spontaneously regenerated tissue in meniscectomised animals had even lower values. There were no significant differences in values between newly grown perichondral menisci and spontaneously grown tissue

1. Experiments to examine the antigenicity of homologous bone tissues in rats are reported. The tissues studied included fresh marrow-free cortical bone blocks and chips, fresh, boiled, frozen and freeze-dried marrow-containing iliac bone, fresh iliac bone devoid of marrow, and fresh red marrow. 2. The various tissues were transplanted from hooded to Wistar rats. Three weeks later a skin graft from each donor was transplanted to its respective host to detect the presence of transplantation immunity, which was indicated by the early rejection of the skin graft. 3. Homografts of fresh cortical bone evoked transplantation immunity indicating that it contained transplantation antigens which were also in the skin. 4. Homografts of fresh marrow-containing iliac bone also evoked transplantation immunity, which was shown to be caused by the red marrow. 5. Fresh iliac homografts devoid of marrow did not elicit transplantation immunity. This suggests that iliac bone tissue may not contain transplantation antigens or that the small amount of iliac bone inserted was insufficient. 6. Microscopy of the grafts, removed after three weeks, showed that the inflammatory infiltrations around the bone homografts and autografts were not very different, but that the amount of new bone formed was different. The autografts produced a lot of new bone, the homografts only a little. 7. It is suggested that the immune response evoked in the host by the foreign graft impairs the formation of new bone by fresh homografts of cortical blocks, cortical chips and marrow-containing iliac bone. 8. The impairment of new bone formation by homografts of marrow-free iliac bone is discussed. Such bone grafts fail to evoke detectable transplantation immunity. Why these grafts do not form more new homologous bone than the other homografts studied, is not clear. 9. Homografts of boiled and frozen iliac bone do not evoke any detectable change in the sensitivity of the host to donor tissue. 10. Homografts of freeze-dried marrow-containing iliac bone elicit a slight but significant prolongation of the survival of skin homografts. The implication, in terms of modern immunological theory, is that in such grafts certain tissue antigens still persist

Dupuytren’s disease is a chronic inflammatory process which produces contractures of the fingers. The nodules present in Dupuytren’s tissue contain inflammatory cells, mainly lymphocytes and macrophages. These express a common integrin known as VLA4. The corresponding binding ligands to VLA4 are vascular cell adhesion molecule-1 (VCAM-1) present on the endothelial cells and the CS1 sequence of the fibronectin present in the extracellular matrix. Transforming growth factor-beta (TGF-ß) is a peptide hormone which has a crucial role in the process of fibrosis. We studied tissue from 20 patients with Dupuytren’s disease, four samples of normal palmar fascia from patients undergoing carpal tunnel decompression and tissue from ten patients who had received perinodular injections of depomedrone into the palm five days before operation. The distribution of VLA4, VCAM-1, CS1 fibronectin and TGF-ß was shown by immunohistochemistry using an alkaline phosphorylase method for light microscopy. In untreated Dupuytren’s tissue CS1 fibronectin stained positively around the endothelial cells of blood vessels and also around the surrounding myofibroblasts, principally at the periphery of many of the active areas of the Dupuytren’s nodule. VCAM-1 stained very positively for the endothelial cells of blood vessels surrounding and penetrating the areas of high nodular activity. VCAM-1 was more rarely expressed outside the blood vessels. VLA4 was expressed by inflammatory cells principally in and around the blood vessels expressing VCAM-1 and CS1 but also on some cells spreading into the nodule. TGF-ß stained positively around the inflammatory cells principally at the perivascular periphery of nodules. These cells often showed VLA4 expression and co-localised with areas of strong production of CS1 fibronectin. Normal palmar fascia contained only scanty amounts of CS1 fibronectin, almost no VCAM-1 and only an occasional cell staining positively for VLA4 or TGF-ß. In the steroid-treated group, VCAM-1 expression was downregulated in the endothelium of perinodular blood vessels and only occasional inflammatory cell expression remained. Expression of CS1 fibronectin was also much reduced but still occurred in the blood vessels and around the myofibroblast stroma. VLA4-expressing cells were also reduced in numbers. A similar but reduced distribution of production of TGF-ß was also noted. Our findings show that adherence of inflammatory cells to the endothelial wall and the extravasation into the periphery of the nodule may be affected by steroids, which reduce expression of VCAM-1 in vivo. This indicates that therapeutic intervention to prevent the recommencement of the chronic inflammatory process and subsequent fibrosis necessitating further surgery may be possible

Aims

The purpose of this study was to evaluate the biological fixation of a 3D printed porous implant, with and without different hydroxyapatite (HA) coatings, in a canine model.

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.