Objectives. We studied subchondral intraosseous pressure (IOP) in an animal model during loading, and with vascular occlusion. We explored bone compartmentalization by saline injection. Materials and Methods. Needles were placed in the femoral condyle and proximal tibia of five anaesthetized rabbits and connected to pressure recorders. The limb was loaded with and without proximal vascular occlusion. An additional subject had simultaneous triple recordings at the femoral head, femoral condyle and proximal tibia. In a further subject, saline injections at three sites were carried out in turn. Results. Loading alone caused a rise in subchondral IOP from 11.7 mmHg (. sd. 7.1) to 17.9 mmHg (. sd. 8.1; p < 0.0002). During arterial occlusion, IOP fell to 5.3 mmHg (. sd. 4.1), then with loading there was a small rise to 7.6 mmHg (. sd. 4.5; p < 0.002). During venous occlusion, IOP rose to 20.2 mmHg (. sd. 5.8), and with loading there was a further rise to 26.3 mmHg (. sd. 6.3; p < 0.003). The effects were present at three different sites along the limb simultaneously. Saline injections showed pressure transmitted throughout the length of the femur but not across the knee joint. Conclusion. This is the first study to report changes in IOP in vivo during loading and with combinations of vascular occlusion and loading. Intraosseous pressure is not a constant. It is reduced during proximal arterial occlusion and increased with proximal venous occlusion. Whatever the perfusion state, in vivo load is transferred partly by hydraulic pressure. We propose that joints act as hydraulic pressure barriers. An understanding of subchondral physiology may be important in understanding osteoarthritis and other bone diseases. Cite this article: M. Beverly, S. Mellon, J. A. Kennedy, D. W. Murray. Intraosseous pressure during loading and with vascular occlusion in an animal model. Bone Joint Res 2018;7:511–516. DOI: 10.1302/2046-3758.78.BJR-2017-0343.R2

Abstract. Background. Schwannomas are slow-growing, benign tumours normally originating from the Schwann cells of the nerve sheath. Intraosseous schwannoma accounts for 0.175% of primary bone tumours and extremely rare especially outside the axial skeleton. Monoclonal gammopathy has been associated with soft tissue schwannomas but never with the intraosseous variety. Presenting problem. A 55-year-old woman with a background of monoclonal gammopathy of undetermined significance (MGUS) presented with a 2-year history of right thigh pain. CT scan showed a well defined, lytic lesion with a thin peripheral rim of sclerosis in the midshaft of the femur. MRI displayed a hyperintense, well marginated and homogenous lesion. Definitive diagnosis was made based on the classical histopathological appearance of schwannoma. Clinical management. We managed our patient with local curettage and prophylactic cephalomedullary nailing on the basis of a high mirel score. Discussion. Intraosseous schwannomas are poorly understood but most commonly reported in middle-aged women. Radiologically, their differential diagnosis includes malignant bone tumours, solitary bone cysts, aneurysmal bone cysts and giant cell tumours. As a result, they are usually diagnosed incidentally on histology. Although malignant transformation is possible in soft tissue schwannomas, all intraosseous schwannomas reported to date have been benign. This case demonstrates the importance of suspecting intraosseous schwannoma as a differential diagnosis for lytic bone lesions to avoid the overtreatment of patients. We also highlight monoclonal gammopathy of undetermined significance as a potential risk factor for a poorly understood disease and make recommendations about the appropriate management of these lesions. Declaration of Interest. (b) declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research reported:I declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research project

Intraosseous Transcutaneous Amputation Prosthesis (ITAP) is a new generation of limb replacements that can provide to amputees, an alternative solution to the main problems caused by the most common used external prosthesis such as pressure sores, infections and unnatural gait. ITAP is designed as one pylon osteointegrated into the bone and protruding through the skin, allowing both the mechanical forces to be directly transferred to the skeleton and the external skin being free from frictions and infections. The skin attachment to the implant is fundamental for the success of the ITAP, as it prevents the implant to move and consequently fail. In this study we wanted to test if cell viability and attachment was improved using TiO2 nanotubes. Human keratinocytes and human dermal fibroblasts were seeded for three days on TiO2 nanotubes with different sizes (18–30nm, 40–60nm and 60–110nm), compared with controls (smooth titanium) and tested for viability and attachment. A Mann-Whitney U test was used to compare groups where p values < 0.05 were considered significant. The results showed that the viability and cell attachment for keratinocytes were significantly higher after three days on controls comparing with all nanotubes (p=0.02), while attachment was higher on bigger nanotubes and controls. Cell viability for fibroblasts was significantly higher on nanotubes between 40 and 110nm comparing with smaller size and controls (p=0.03), while investigation of cell attachment is ongoing. From these early results, we can say that TiO2 nanotubes can improve the soft tissue attachment on ITAP. Further in-vitro and ex-vivo experiments on cell attachment will be carried out

To try and aid the formation of a soft tissue seal to promote dermal and epidermal attachment to Intraosseous Transcutaneous Amputation Prostheses we compared the effect of titanium surfaces functionalised with fibronectin (fn) or YRGD peptide sequences on human dermal cell (HDF) attachment. We hypothesise that YRGD and fn coatings will significantly increase HDF attachment to titanium alloy substrates. Titanium alloy 10mm discs were polished and acted as control substrates, functionalised surfaces had YRGD or fn adsorbed or silanised onto the polished surface. HDFs were seeded at 10,000/disc and cultured for 1, 4, 24 and 96 hours, fixed and fluorescent immnolocalisation for vinculin was performed. Individual vinculin markers were counted and density calculated as a measure of cell attachment. All assays were performed in triplicate and data were analysed in SPSS 19.0 and results were considered significant at the 0.05 level. Results showed an up-regulation of Focal adhesion density (FA) against controls at all time-points (excluding ad-fn at 4 hours, p=0.057), p values < 0.05, the use of functionalised titanium surfaces may lead to long-term clinical success of ITAP. We have shown a significant positive effect on cell attachment when a synthetic peptide sequence is used. Using synthetic peptide sequence may also be more beneficial from a regulatory stand-point compared with using isolated proteins

Infection is the primary failure modality for transcutaneous implants because the skin breach provides a route for pathogens to enter the body. Intraosseous transcutaneous amputation prostheses (ITAP) are being developed to overcome this problem by creating a seal at the skin-implant interface to prevent bacterial invasion. Oral gingival epithelial cell adhesion creates an infection free seal around dental implants; however this has yet to be demonstrated outside the oral environment. All epithelial cells attach via hemidesmosomes (HD) and focal adhesions (FA) and their expression is an indicator of adhesion efficiency. The aim of this study was to compare epidermal keratinocyte with oral gingival epithelial cell adhesion on titanium alloy in vitro to determine whether these two cell types differ in their speed and strength of adhesion. It was hypothesised that oral gingival epithelial cells attach to titanium alloy earlier than epidermal keratinocytes; with greater expression of hemidesmosomes and focal adhesions. Human oral gingival epithelial cell (HGEP) and primary human epidermal keratinocyte (HPEK) adhesion to titanium alloy, was assessed at 4, 24, 48 and 72 hrs. Adhesion was measured by the number of FAs per unit cell area and expression of HDs using a semi-quantitative scale. At 4 and 24hrs, there was a significant increase in vinculin marker expression per unit cell area of 4.3 and 4.7 times in HGEP compared with HPEK (p=0.000). At 48 and 72hrs there were no significant differences. HD expression was significantly greater in HGEP at 4 and 24hrs (p=0.002) compared with HPEK. Up-regulation of HD expression in HPEK lagged that of HGEP until 48hrs, after which no significant differences were observed. This study has demonstrated that oral gingival cells up-regulate both focal adhesion and hemidesmosome expression at earlier time points compared with epidermal keratinocytes. Expression of hemidesmosomes lags that of focal adhesions, suggesting that focal adhesion formation is a prerequisite for hemidesmosome assembly. We postulate that early attachment of oral gingival epithelial cells to dental implant biomaterials may be responsible for the formation of an infection-free seal

The purpose of this study is to enhance massive bone allografts osseointegration used to reconstruct large bone defects. These allografts show >50% complication rate requiring surgical revision in 20% cases. A new protocol for total bone decellularisation exploiting the vasculature can offer a reduction of postoperative complication by annihilating immune response and improving cellular colonization/ osseointegration. The nutrient artery of 18 porcine bones - humerus/femur/radius/ulna - was cannulated. The decellularization process involved immersion and sequential perfusion with specific solvents over a course of one week. Perfusion was realized by a peristaltic pump (mean flow rate: 6ml/min). The benefit of arterial perfusion was compared to a control group kept in immersion baths without perfusion. Bone samples were processed for histology (HE, Masson's trichrome and DAPI for cell detection), immunohistochemistry (IHC : Collagen IV/elastin for intraosseous vascular system evaluation, Swine Leukocyte Antigen – SLA for immunogenicity in addition to cellular clearance) and DNA quantification. Sterility and solvent residues in the graft were also evaluated with thioglycolate test and pH test respectively. Compared to native bones, no cells could be detected and residual DNA was <50ng/mg dry weight. Intramedullary spaces were completely cleaned. IHC showed the preservation of intracortical vasculature with channels bounded by Collagen IV and elastin within Haversian systems. IHC also showed a significant decrease in SLA signaling. All grafts were sterile at the last decellularization step and showed no solvent residue. The control group kept in immersion baths, paired with 6 perfused radii/ulnae, showed that the perfusion is mandatory to ensure complete decellularisation. Our results prove the effectiveness of a new concept of total bone decellularisation by perfusion. These promising results could lead to a new technique of Vascularized Composite Allograft transposable to pre-clinical and clinical models

Introduction. The crescent sign is thought to be an early indicator of collapse in osteonecrosis of the femoral head. However, the formation mechanism of the crescent sign is still not quite clear. The purpose of this study was to utilize the two-dimensional finite element model analysis (FEA) technique to analyze mechanical function of different structures and intraosseous fluid in the femoral head under the stress of physiological loading. We wished to answer the following question: which structure or structures' failure are the main causes of collapse in osteonecrosis of the femoral head (ONFH)?. Methods. Based on two femoral head specimens obtained during THA (one with osteonecrosis of the femoral head with crescent sign formation and the other with most of the cancellous bone eroded by tumor cells without collapse), three groups of ten models were designed. Group A were standard femoral heads composed of subchondral plate, cancellous bone, intraosseous fluid, and cortical bone with 50 mm in diameter, Group B included ONFH, and Group C was based on a tumor-eroded femoral head. Previously reported mechanical property parameters were used in the FEA calculation. The strain and Von Mieses stress mechanics parameters of fifteen points (with the same coordinates) in the junction between subchondral plate and cancellous bone were harvested and compared. Results. In the model, Group B3 (around the fissure region), had strains 12 times and Von Mieses' stresses 4.5 times higher than the values in same region of Group A1. Strain and Von Mieses stresses were concentrated in the fissure region and in the junction of the subchondral plate and the cancellous bone of the necrotic region. Conclusion. All three; the subchondral plate, cancellous bone, and intraosseous fluid, together played an important role for the femoral head to bear physiological loads. It is the fissure in the subchondral plate caused by the resorption that; 1) provides a channel for the intraosseous fluid to outflow and makes the necrotic region in both the subchondral plate and the cancellous bone lose mechanical support from the intraosseous fluid, and 2) destroys the function of the subchondral plate as a thin shell structure, making the stress and strain concentrate in the junction of the subchondral plate and the cancellous bone of the necrotic region. Concentrated stress leads to fracture of the junction between the subchondral plate and the cancellous bone and the formation of a crescent sign

Remodeling of the cancellous bone is more active than that of the cortical bone. It is known that the remodeling is governed by the intracancellous fluid pressure. Particularly, the lacunocanalicular pore (PLC) fluid pressure (FP) is essential for survival of the osteocyte and communication of remodeling signals between the PLC and intertrabecular pore (PIT). As a result, knowledge about the PLCFP generation of trabeculae is required to understand human cancellous bone biology. At this moment, the PLCFP measurement of human trabeculae is not reported. The purpose of this study was a direct measurement of PLCFP generation of human proximal femoral trabeculae in the direction of superior-to-fovea. Twenty one microscopic cylindrical trabecular specimens from trabeculae of five fresh human proximal femur (75 to 77 years) were fabricated using a micro-milling machine composed of the laser (Teemphotonics: 532nm), 3-dimensional PZT stage (PI Gmbh, resolution: 0.5nm), and microscope (lens: Navitar, and CCD: Hitachi) with the image processor. The fabrication resolution of the micro-milling machine was 0.4 um. Based on the trabecular trajectory of femoral head, the specimens were obtained in the direction of superior-to-fovea. The cylindrical specimen size had 120 um in diameter and 240 um in length. The test methods described in the previous study were utilized. The used undrained uniaxial strain condition could induce the maximum PLCFP within the trabecular elastic limit. The measured trabecular PLCFP (±SD) at the strain of 0.4% was 693.7±79.1 kPa. Since this experiment is equivalent to the instantaneous response of PLCFP with free flow boundaries after application of an extremely fast loading speed such an ideal step loading, a PLCFP generation in the physiological condition will be much less than the results obtained in this study. Base on the linear isotropic poroelasticity, the obtained Skempton's coefficient is almost 0. Thus, the load bearing capability by trabecular PLC fluid is negligible. The Biot coefficient is 0.35 which is higher than that of the cortical tissue (0.14). As a result, the intraosseous fluid communication through trabecular surfaces is active compared to that through Haversian canal surfaces. This imply that mass transports from the trabecular PLC into the PIT and from the PIT into the trabecular PLC could be significantly affected by the PITFP (the physiological blood systolic and diastolic pressure: 16 and 11 kPa, respectively) that acts as the FP boundary condition for the PLC flow. It is known that the PLC flow generates the electrical charges on the trabecular surface (‘+’ for being spouted into the PIT and ‘−’ for being flown into the PLC), which control differentiation and proliferation of the osteoblast and mesenchymal stem cell. Thus, significant changes in the PITFT could cause changes in the intra-trabecular PLC flow characteristics, mass transports between the PLC and PIT, and electrical charges on the trabeculae. Eventually, these could result in pathologies related to the trabecular remodeling

Femoral neck fractures remain the leading cause of early failure after metal-on-metal hip resurfacing. Although its' exact pathomechanism has yet to be fully elucidated, current retrieval analysis has shown that either an osteonecrotic event and/or significant surgical trauma to the femoral head neck junction are the leading causes. It is most likely that no single factor like patient selection and/or femoral component orientation can fully avoid their occurrence. As in osteonecrosis of the native hip joint, a certain cell injury threshold may have to be reached in order for femoral neck fracture to occur. These insults are not limited to the surgical approach, but also include femoral head preparation, neck notching, and cement penetration. Although some have argued that the posterior approach does not represent an increased risk fracture for ON after hip resurfacing because of the so-called intraosseous blood supply to the femoral head, to date, the current body of literature on femoral head blood flow in the presence of arthritis has confirmed the critical role of the extraosseous blood supply from the ascending branch of the medial circumflex, as well as the lack of any substantial intraosseous blood supply. Conversely, anterior hip dislocation of both the native hip joint as well as the arthritic hip preserves femoral head vascularity. The blood supply can be compromised by either sacrificing the main branch of the ascending medial femoral circumflex artery or damaging the retinacular vessels at the femoral head-neck junction. Thus an approach which preserves head vascularity, while minimizing soft tissue disruption would certainly be favorable for hip resurfacing. This presentation will review the current state of knowledge on vascularity of the femoral head as well as surgical techniques enhancing its preservation

OA pathophysiology has a vascular component consisting of venous stasis resulting in intraosseous hypertension and hypoxia. In response, osteoblasts change their cytokine expression, accelerating bone remodelling and cartilage breakdown consistent with OA. We have characterized circulatory kinetics in OA bone in animal models with dynamic contrast enhanced MRI (DCE-MRI) and . 18. F PET and have demonstrated venous stasis and reduced perfusion that temporally precede and spatially coincide with OA lesions. Osteoblast uptake of . 18. F is consistent with abnormal perfusion, bone remodelling, and severity of OA. Circulatory kinetics with DCE-MRI in humans with OA of the knee exhibit similar venous outflow obstruction. Venous stasis is associated with hypoxia in subchondral bone. As an example of the effects of hypoxia on OA osteoblasts, we have described upregulation of fibrinolytic peptides, but a deficiency in the upregulation of PAI-1, leading to the generation of plasmin by human OA osteoblasts exposed to hypoxia in vitro. Plasmin is a serine protease that has been shown to degrade cartilage in OA. Abnormal circulatory kinetics by DCE-MRI may be an imaging biomarker of OA. Pharmacologic modulation of venous stasis would have a salutary effect on the physicochemical microcirculation of subchondral osteoblasts and the pathophysiology of OA

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

Primary bone tumours of the talus are rare. Currently the existing literature is limited to a single case series and case reports or cases described in series of foot tumours. Information regarding the patient's demographics and tumour types is therefore limited. The aim of this study was to investigate these questions and also suggest a management protocol for suspected primary bone tumours of the talus. We retrospectively reviewed the Scottish Bone Tumour Register from January 1954 to May 2010 and included all primary bone tumours of the talus. We identified only twenty three bone tumours over fifty six years highlighting the rarity of these tumours. There were twenty benign and three malignant tumours with a mean age of twenty eight years. A delay in presentation was common with a mean time from onset of symptoms to diagnosis of ten months. Tumour types identified were consistent with previous literature. We identified cases of desmoplastic fibroma and intraosseous lipodystrophy described for the first time. We suggest an investigatory and treatment protocol for patients with a suspected primary bone tumour of the talus. This is the largest series of primary bone tumours of the talus in the literature

The aim of this study was to determine the effectiveness of antibiotic-impregnated implants in the prevention of bone infection. We used a model of contaminated fracture in goats to evaluate four treatment groups: no treatment, hand-made tobramycin-impregnated polymethylmethacrylate beads, commercially-available tobramycin-impregnated calcium sulphate pellets and commercially-available tobramycin-impregnated polymethylmethacrylate beads. Three weeks after intraosseous inoculation with streptomycin-resistant Staphylococcus aureus tissue cultures showed no evidence of infection in any of the antibiotic-treated groups. All of the cultures were positive in the untreated group. These results show that effective local antibiotic delivery can be obtained with both commercially-available products and with hand-made polymethylmethacrylate beads. The calcium sulphate pellets have the advantage of being bioabsorbable, thereby obviating the need for a second procedure to remove them

Introduction. The treatment osteonecrosis of the femoral head remains uncertain. Core decompression is the standard technique for the early stages (ARCO I and II). A new alternative is core decompression combined with the insertion of an osteonecrosis rod. This implant is supposed to reduce the intraosseous pressure and to give additional structural support. The aim of this study was to evaluate the clinical and radiological outcome via magnetic resonance imaging (MRI) of this new technique. Methods. Twenty-three patients were included in this study. All patients underwent a core decompression combined with the insertion of an osteonecrosis rod. Results. A survival rate of 44 % (10 of 23 patients) was found. The conversion to a total hip arthroplasty was performed after a mean interval of 529 days (range, 120 to 1348 days) because of persistence of pain or destruction of the joint. In five cases, a conversion to a long-stem hip arthroplasty, in seven cases to a short-stem arthroplasty, and in one case in an external hospital, to a hip resurfacing was performed. The majority of patients within the surviving group revealed an almost unchanged stage (mean follow-up of 477 days). In two cases, a radiological regression was obvious. A follow-up MRI of one of those patients showed complete regression. Conclusion. The outcome after core decompression combined with the insertion of a tantalum osteonecrosis intervention implant did not show superior results compared to core decompression. This is in contrast to prior studies. In addition, the surgical procedure and rehabilitation was prolonged and the costs higher than for isolated core decompression. An advantage is low risk of fracture post-operatively. In the case of conversion to total hip arthroplasty, no problems appeared during explantation of the tantalum implant

Our aim was to determine whether tantalum markers improved the accuracy and/or precision of methods for the measurement of migration in total hip replacement based on conventional measurements without mathematical correction of the data, and with Ein Bild Roentgen Analyse – Femoral Component Analysis (EBRA-FCA) which allows a computerised correction. Three observers independently analysed 13 series of roentgen-stereophotogrammetric-analysis (RSA)-compatible radiographs (88). Data were obtained from conventional measurements, EBRA-FCA and the RSA method and all the results were compared with the RSA data. Radiological evaluation was also used to quantify in how many radiographs the intraosseous position of the bone markers had been simulated. The results showed that tantalum markers improve reliability whereas they do not affect accuracy for conventional measurements and for EBRA-FCA. Because of the danger of third-body wear their implantation should be avoided unless they are an integral part of the method

Bone marrow is an environment rich in its diversity of cell types and niches. Both hematopoietic and osteogenic stromal cells are present and have been studied extensively. Less is known about the function of one of the most abundant cell types in the bone marrow: adipocytes. There are several hypotheses that have been proposed including: passive role as a space filler; active role in the body's general lipid metabolism; role in providing a localized energy reservoir for emergency situations affecting the bone or hematopoiesis; support of differentiation or function of other cell types (such as bone, endothelial, and other stromal cells). There are several human pathologies associated with increases in adipocyte hypertrophy or proliferation including changes associated with aging, osteoporosis, and osteonecrosis. The reasons for these changes are poorly understood. One etiology associated with both osteoporosis and osteonecrosis, corticosteroid therapy, has been shown to increase the lipid content of osteoblasts and adipocytes. With osteonecrosis, several pathogenetic mechanisms involving adipocytes have been proposed:. Mechanical - increased size and number cause increased intraosseous pressure and decreased venous outflow. Direct precursor cells away from osteoblastogenesis towards adipogenesis. Liquid fat causing a hypercoagulable state. Osteocyte dysfunction or apoptosis. Adipocyte and bone marrow necrosis. Release adipokines and other factors that have an effect on the cells within the bone marrow (inhibiting angiogenesis, e.g.). The possibility that adipocytes may actually play an active role in propagating specific pathologic features has only recently been discussed. This is in part due to our increasing understanding that adipocytes have an endocrine role in metabolism. Only recently have scientists tried to identify specific cellular mechanisms that may be involved in the pathogenesis of osteonecrosis. Results from these studies will not only contribute to our understanding of the disease of osteonecrosis (and other diseases such as osteoporosis) but will also help us to appreciate the multiple functionalities of the heretofore unappreciated adipocyte

Summary Statement. OA knee with subchondral cyst formation presented differential microstructure and mechanical competence of trabecular bone. This finding sheds light on the pivot role of subchondral cyst in OA bone pathophysiology. Introduction. Subchondral bone cyst (SBC) is a major radiological finding in knee osteoarthritis (OA), together with joint space narrowing, osteophyte and sclerotic bone formation. There is mounting evidence showing that SBC originates in the same region as bone marrow lesions (BMLs). The presence of subchondral bone cyst (SBCs), in conjunction with BMLs, was associated with the severity of pain, and was able to predict tibial cartilage lolume loss and risk of joint replacement surgery in knee OA patient. It is speculated that the presence of SBCs might increase intraosseous pressure of subchondral bone, and trigger active remodeling and high turnover of surrounding trabecular bone. Yet the exact effect of SBC on the structural and mechanical properties trabecular bone, which provides the support to overlying articular cartilage, remains to be elucidated. Therefore, this study aimed to investiate the microstructure and mechanical competence of trabecular bone of knee OA in presence or absence of SBC. Patients & Methods. A total of 20 postmenopausal women (54–87 years old) with the late-stage of primary knee OA were recruited in this study. Tibial plateau specimens were collected during joint replacement surgery. The samples were grouped for comparison according to presence or absences of SBC in micro-CT images. For micro-CT examination, a cylindrical volume of region of interest (VOI) of 10mm in diameter and 1mm in height was used to cover the trabecular bone region surrounding SBC, and then a cubic VOI of 3.5×3.5×3.5mm. 3. was applied in different anatomic locations of tibial plateau, such as medial, intermediate and lateral part, for the analyses of trabecular bone microstructure. Subsequently, two cylinders of subchondral bone specimens were drilled for each sample with micro-CT guidance from lateral portion of cystic wall along the direction of physiological loading of knee joint. The specimens were processed for micro-CT and mechanical testing using MTS 858 Mini Bionix sequentially. Each specimen was compressed in a longitudinal direction at a speed of 1mm/minute; the ultimate strength and modulus of the specimens were generated. Comparisons of microstructure and mechanical properties of trabecular bone were performed between two groups using student t test. The structure-mechanics relationship was also investigated using Pearson correlation. Results. The bone volume fraction (BV/TV, %) was significantly higher in knee OA specimens in presence of SBC (32±7%) in comparison with those in absence of SBC (16±5%, p<0.001). Meanwhile there were more plate-like trabecular bone surrounding SBC (0.78±0.61) than those without SBC (1.81±0.28, p<0.001), which was indicated by structure model index (0∼3). Furthermore, the trend in conversion of rod-like (close to 3) towards plate-like trabeculae was noticed in different locations of knee OA specimens with SBC formation. Trabecular bone around SBC presented higher modulus (73±22MPa) compared with those without SBC (45±29MPa, p=0.034). The stiffer trabecular bone in presence of SBC correlated with its plate-like morphology (r=0.696, p<0.001) as well as bone volume fraction (r=0.578, p=0.004). Conclusion. Presence of SBC was associated with conversion of trabeculae towards plate-like morphology together with the increase of mechanical competence in advanced knee OA

Summary Statement. A porcine model using Yucatan minipigs was found to be very promising for the investigation of healing around transcutaneous osseointegrated implants. Pigs demonstrated surprising agility and adaptability including the ability to ambulate on three legs during the immediate postoperative period. Introduction. Previous non weight-bearing and weight-bearing caprine, canine and ovine models have evaluated design, material, and biological coating variations in an attempt to improve the wound healing and skin-implant seal around transcutaneous osseointegrated implants. Although these models have primarily been used as a window into the application of transcutaneous osseointegrated implants in humans, some important model characteristics affecting wound healing and infection have been missing including: 1) replication of the physiological tissue response, and 2) availability of a transcutaneous site with sufficient soft tissue coverage. Pig skin, like human, is relatively hairless, tightly attached to the subcutaneous tissue, vascularised by a cutaneous blood supply, and healed by means of epithelialization. Swine have been extensively utilised for superficial and deep wound healing studies and can offer ample soft tissue coverage following a lower limb amputation. Development of a porcine model is important for continued understanding and improvement of weight-bearing transcutaneous osseointegration. Methods. Two male Yucatan mini-pigs (9 months, 36kg) were fit with transcutaneous osseointegrated prostheses using a single-stage transtibial amputation and prosthesis implantation procedure. The endo-prosthesis consisted of a cylindrical intraosseous threaded section and a smooth transcutaneous section. The transcutaneous sections were smooth to promote epithelialization and deter direct skin-implant adhesion. The implants were custom manufactured from medical grade Ti-6Al-4V alloy. The exo-prosthesis, consisting of an adjustable length leg and foot, was attached by clamp to the supercutaneous portion of the implant following either one or two days of sling constraint to limit initial weight-bearing. Various exo-prosthesis designs and configurations were trialed. The animals’ behavior and gait were closely observed. Weight-bearing was monitored using a force plate. At 5 and 8 weeks, clinical, microbiological, and histological data were examined to assess wound healing and infection at the skin-bone-implant interface. Results. The pigs demonstrated surprising agility and adaptability. They were able to successfully ambulate on three legs during the post-op period before weight-bearing was permitted. They adapted quickly to changes in exo-prosthesis design, position, and length. Although bacterial colonization was verified, neither of the animals exhibited clinical signs of infection over the respective eight and five week studies. Histological results indicated that there was no skin to implant adhesion but that epithelial growth was progressing towards the implant in one animal. Healing of the transcutaneous wound site showed substantial progress but a definitive skin seal was non-existent at the eight week time point. Discussion/Conclusion. This is likely the first animal model developed, having soft tissue characteristics similar to those found in humans, in which an axially-loaded, weight-bearing implant was successfully used. Results indicated that this porcine model offers many advantages over previous models for the development, evaluation, and comparison of the various techniques being advocated to achieve successful transcutaneous osseointegration in humans. The Yucatan miniature pig's ability to ambulate on three legs during the immediate post-operative period and quickly adjust to changes in the exo-prosthesis design, coupled with their physiological similarity to humans, makes them a valuable model for future studies

Platelet-leucocyte gel (PLG), a new biotechnological blood product, has hitherto been used primarily to treat chronic ulcers and to promote soft-tissue and bone regeneration in a wide range of medical fields. In this study, the antimicrobial efficacy of PLG against Staphylococcus aureus (ATCC 25923) was investigated in a rabbit model of osteomyelitis. Autologous PLG was injected into the tibial canal after inoculation with Staph. aureus. The prophylactic efficacy of PLG was evaluated by microbiological, radiological and histological examination. Animal groups included a treatment group that received systemic cefazolin and a control group that received no treatment.

Treatment with PLG or cefazolin significantly reduced radiological and histological severity scores compared to the control group. This result was confirmed by a significant reduction in the infection rate and the number of viable bacteria. Although not comparable to cefazolin, PLG exhibited antimicrobial efficacy in vivo and therefore represents a novel strategy to prevent bone infection in humans.

Although much has been published on the causes of slipped upper femoral epiphysis and the results of treatment, little attention has been given to the mechanism of the slip. This study presents the results of the analysis of 13 adolescent femora, and the attempts to reproduce the radiological appearances of a typical slip. The mean age of the skeletons was 13 years (11 to 15). It was found that the internal bony architecture in the zone of the growth plate was such that a slip of the epiphysis on the metaphysis (in the normal meaning of the word slip) could not take place, largely relating to the presence of a tubercle of bone projecting down from the epiphysis. The only way that the appearance of a typical slipped upper femoral epiphysis could be reproduced was by rotating the epiphysis posteromedially on the metaphysis. The presence and size of this peg-like tubercle was shown radiologically by CT scanning in one pair of intact adolescent femurs.