A foreign-body-type host response can contribute to the induction and release of collagenolytic tissue-destructive enzymes of pathogenetic significance. Our aim was to analyse collagenase-3 in two conditions with putative involvement of foreign-body reactions. Synovial membrane-like tissue samples were obtained from cases of aseptic loosening of a total hip replacement (THR) and osteoarthritis (OA).

The reverse transcription polymerase chain reaction (RT-PCR) disclosed that all the samples from patients contained collagenase-3 mRNA compared with only three out of ten control samples. The identity of the RT-PCR amplification product was confirmed by nucleotide sequencing. Immunohistochemical staining showed that collagenase-3 was present in endothelial cells, macrophages and fibroblasts, including those found in the synovial lining. This finding was confirmed by avidin-biotin-peroxidase complex-alkaline phosphatase-anti-alkaline phosphatase double staining and the specificity of the staining by antigen preabsorption using recombinant human collagenase-3.

Collagenase-3 was released into the extracellular space and thus found in the synovial fluid in all patient samples as shown by Western blotting. The similar extent of collagenase-3 expression in aseptic loosening and OA compared with the low expression in control synovial membrane suggests involvement of a similar, foreign-body-based pathogenetic component in both. Comparative analysis of collagenase-3 and of foreign particles indicates that paracrine factors rather than phagocytosis per se are responsible for the induction of collagenase-3.

We suggest that due to its localisation and substrate specificity, collagenase-3 may play a significant pathogenetic role in accelerating tissue destruction in OA and in aseptic loosening of a THR.

Spinal surgery deals with the treatment of different pathological conditions of the spine such as tumors, deformities, degenerative disease, infections and traumas. Research in the field of vertebral surgery can be divided into two main areas: 1) research lines transversal to the different branches; 2) specific research lines for the different branches. The transversal lines of research are represented by strategies for the reduction of complications, by the development of minimally invasive surgical techniques, by the development of surgical navigation systems and by the development of increasingly reliable systems for the control of intra-operative monitoring. Instead, specific lines of research are developed within the different branches. In the field of oncological pathology, the current research concerns the development of in vitro models for the study of metastases and research for the study of targeted treatment methods such as electrochemotherapy and mesenchymal stem cells for the treatment of aneurysmal bone cysts. Research in the field of spinal deformities is focused on the development of increasingly minimally invasive methods and systems which, combined with appropriate pharmacological treatments, help reduce trauma, stress and post-operative pain. Scaffolds based on blood clots are also being developed to promote vertebral fusion, a fundamental requirement for improving the outcome of vertebral arthrodesis performed for the treatment of degenerative disc disease. To improve the management and the medical and surgical treatment of vertebral infections, research has focused on the definition of multidisciplinary strategies aimed at identifying the best possible treatment path. Thus, flow-charts have been created which allow to manage the patient suffering from vertebral infection. In addition, dedicated silver-coated surgical instrumentation and bone substitutes have been developed that simultaneously guarantee mechanical stability and reduce the risk of further local infection. In the field of vertebral traumatology, the most recent research studies have focused on the development of methods for the biostimulation of the bone growth in order to obtain, when possible, healing without surgery. Methods have also been developed that allow the minimally invasive percutaneous treatment of fractures by means of vertebral augmentation with PMMA, or more recently with the use of silicone which from a biomechanical point of view has an elastic modulus more similar to that of bone. It is clear that scientific research has changed clinical practice both in terms of medical and surgical management of patients with spinal pathologies. The results obtained stimulate the basic research to achieve even more. For this reason, new lines of research have been undertaken which, in the oncology field, aim at developing increasingly specific therapies against target receptors. Research efforts are also being multiplied to achieve regeneration of the degenerated intervertebral disc and to develop implants with characteristics increasingly similar to those of bone in order to improve mechanical stability and durability over time. Photodynamic therapies are being developed for the treatment of infections in order to reduce the use of antibiotic therapies. Finally, innovative lines of research are being launched to treat and regenerate damaged nerve structures with the goal, still far from today, of making patients with spinal cord injuries to walk

The stem cell fraction of a cell population is finely tuned by stimuli from the external microenvironment. Among these stimuli, a decrease of extracellular pH (pHe) may occur in a variety of physiological and pathological conditions, including hypoxia and inflammation. Also in bone, the maintenance of acid-base balance is fundamental for skeleton homeostasis. Bone cells are extremely sensitive to the effects of interstitial pH. Acidosis inhibits mineral deposition by osteoblasts and activates osteoclast-mediated bone resorption. Moreover, acidosis is associated with inflammation, and in case of bone injury, local short-term acidosis is a crucial regulator of the healing process. Evidence of the role of acidosis as an enhancer of MSC stemness and for their activation as sensors and switcher of inflammation will be discussed

The Cochrane Collaboration has produced five new reviews relevant to bone and joint surgery since the publication of the last Cochrane Corner These reviews are relevant to a wide range of musculoskeletal specialists, and include reviews in Morton’s neuroma, scoliosis, vertebral fractures, carpal tunnel syndrome, and lower limb arthroplasty.

Background. Mechanisms underlying implant failure remain incompletely described, though the presence of macrophage-mediated inflammatory reactions is well documented. Hypoxia has a critical role in many diseases and is known to be interdependent with inflammation. Metals used for joint replacements have also been reported to provoke hypoxia-like conditions. In view of this, we aim to investigate hypoxia-associated factors in aseptic loosening and osteoarthritis with a focus on macrophages. Methods. Western blotting, calorimetric assay, haematoxylin-eosin staining, immunohistochemistry, double-immunofluorescence and transmission electron microscopy were performed on capsular tissue obtained from patients undergoing primary implantation of a total hip replacement for osteoarthritis and from patients undergoing revision surgery for aseptic loosening to investigate the presence of hypoxia-associated factors. Results. Tissues from patients with osteoarthritis and aseptic loosening showed the presence of inflammatory cells, many of which were macrophages as confirmed with CD68 immunostaining. In aseptic loosening, macrophages containing metal particles were present in clusters. This was observed both at the light and electron microscopic levels. Under the electron microscope, endothelial cells appeared to be hypertrophied and some showed signs of degeneration. The presence of hypoxia-inducible factor-1α (HIF-1α), vascular endothelial growth factor (VEGF) and nitric oxide was demonstrated by western blotting and colorimetric assay. Macrophages were the predominant cell type to release HIF-1α, VEGF, inducible nitric oxide synthase (iNOS). This was confirmed by double-immunofluorescence showing co-localization of HIF-1α, VEGF, iNOS with the macrophage marker CD68. Endothelial cells were stained for endothelial nitric oxide synthase as assessed by immunohistochemistry. Conclusion. This study demonstrates the release of hypoxia-associated factors by macrophages. The presence of hypoxia-associated factors in both, osteoarthritis and aseptic loosening suggest that hypoxia may be a factor underlying both pathologic conditions. This study was supported by research grant (NMRC/CNIG/1147/2016) from National Medical Research Council (NMRC), Singapore

Cartilage injury is generally associated with cytokine release and accumulation of reactive oxygen species. These mediators trigger pathologic behaviour of the surviving chondrocytes, which respond by excessive expression of catabolic enzymes, such as matrix metalloproteinase 13 (MMP-13), reduced synthesis of type II collagen (COL2A1) and apoptosis. In the long run, these pathologic conditions can cause a posttraumatic osteoarthritis. With the objective to attenuate the progressive degradation of the extracellular matrix and, what is more, promote chondroanabolic processes, a multidirectional treatment of trauma-induced pathogenesis was tested for the first time. Therefore, we evaluated the combinations of one anabolic growth factor (IGF-1, FGF18 or BMP7) with the antioxidant N-acetyl cysteine (NAC) in a human ex vivo cartilage trauma model and compared the findings with the corresponding monotherapy. Human cartilage tissue was obtained with informed consent from donors undergoing knee joint replacement (n=24). Only macroscopically intact tissue was used to prepare explants. Cartilage explants were subjected to a blunt impact (0.59 J) by a drop-tower and treated by IGF-1 [100 ng/mL], FGF18 [200 ng/mL] or BMP7 [100 ng/mL] and/or NAC [2 mM] for 7 days. Following parameters were analysed: cell viability (live/dead staining), gene expression (qRT-PCR) as well as biosynthesis (ELISA) of type II collagen and MMP-13. For statistical analysisKruskal-Wallis or One-way ANOVA was used. All data were collected in the orthopedic research laboratory of the University of Ulm, Germany. Trauma-induced cell death was completely prevented by NAC treatment and FGF18 or BMP7 to a large extent, respectively (p<0.0001). IGF-1 exhibited only poor cell protection. Combination of NAC and FGF18 or BMP7 did not result in enhanced effectiveness; however, IGF-1 significantly reduced NAC-mediated cell protection. While IGF-1 or BMP7 induced collagen type II gene expression (p=0.0069 and p<0.0001, respectively) and its biosynthesis (p<0.0001 and p=0.0131, respectively), NAC or FGF18 caused significant suppression of this matrix component (each p<0.001). Although COL2A1 mRNA was significantly increased by NAC plus IGF-1 (p<0.0001), biosynthesis of collagen type II was generally abolished after multidirectional treatment. Except for IGF-1, all tested therapeutics exhibited chondroprotective qualities, as demonstrated by attenuated MMP-13 expression and breakdown of type II collagen. In combination with IGF-1, NAC-mediated chondroprotection was reduced. Overall, both chondroanabolic and antioxidative therapy had individual advantages. Since adverse interactions were found by simultaneous application of the therapeutics, a sequential approach might improve the efficacy. In support of this strategy current experiments showed that though cell and chondroprotective effects of NAC were maintained after withdrawal of the antioxidant, type II collagen expression recovered by time

Maintenance of acid-base homeostasis in extracellular fluids and in the cytoplasm is essential for the physiological activities of cells and tissues [1]. However, changes in extracellular pH (pHe) occurs in a variety of physiological and pathological conditions, including hypoxia and inflammation associated with trauma and cancer. Concerning bone tissue, if abnormal acidification occurs, mineral deposition and osteoblast differentiation are inhibited, whereas osteoclast formation and activity are enhanced [2]. Indeed, acidification, that usually occurs in the early phases of fracture repair, has been suggested as a driving force for regeneration via release of growth factors that act on the stem cell fraction of repair bone [3]. However, the effect of low pHe on stemness has been insufficiently explored so far. Thus, in this study, we investigated the role of short term exposure to low pHe (6.5–6.8) on MSC stemness. MSC derived from dental pulps (DPSC) and bone marrow (BM-MSC) were used. To perform the specific assays, culture medium at specific pH (6.5, 6.8, 7.1 and 7.4) was maintained by using different concentrations of sodium bicarbonate according to the Henderson-Hasselbach equation. Changes in osteoblast-related gene expression (COL1A1 and ALPL), and mineral nodule formation were measured by qRT-PCR and Alizarin red staining, respectively. The stem phenotype was analysed by measuring changes in stemness-related genes (SOX2, OCT4, KLF4, c-MYC) expression and spheres forming ability. Additionally, cell number, Ki67 index and cell cycle were analysed to monitor cell proliferation and quiescence. We confirmed that acidic pHe inhibits the osteogenic differentiation of DPSC. Low pHe significantly but transitorily decreased the expression of osteoblast-related genes (COL1A1 and ALPL) and decreased the mineral nodule formation in vitro. Acidic pHe conditions significantly increased the ability of DPSC and BM-MSC to form floating spheres. At acidic pHe spheres were higher but smaller when compared to spheres formed at alkaline pHe conditions. Moreover, acidic pHe increased significantly the expression of stemness-related genes. Finally, low pHe induced a significant decrease of DPSC cell number. Reduction of cell proliferation correlated with a lower number of cycling cells, as revealed by the Ki67 index that significantly decreased in a pH-dependent manner. Cell cycle analysis revealed an accumulation of cells in the G0 phase, when cultured at low pH. In this study, we demonstrated a close relationship between acidic pHe and the regulation of MSC stemness. We therefore suggest that pHe modulation of MSC stemness is a major determinant of skeletal homeostasis and regeneration, and this finding should be considered in bone healing strategies based on cell therapy

We analysed the histological findings in 1146 osteoarthritic femoral heads which would have been considered suitable for bone-bank donation to determine whether pathological lesions, other than osteoarthritis, were present. We found that 91 femoral heads (8%) showed evidence of disease. The most common conditions noted were chondrocalcinosis (63 cases), avascular necrosis (13), osteomas (6) and malignant tumours (one case of low-grade chondrosarcoma and two of well-differentiated lymphocytic lymphoma). There were two with metabolic bone disease (Paget’s disease and hyperparathyroid bone disease) and four with inflammatory (rheumatoid-like) arthritis. Our findings indicate that occult pathological conditions are common and it is recommended that histological examination of this regularly used source of bone allograft should be included as part of the screening protocol for bone-bank collection

Background & Objectives. Sensory and motor manifestations in carpal tunnel syndrome (CTS) are well documented, whereas the associated autonomic dysfunction is often overlooked. The aim of this study is to demonstrate that autonomic dysfunction of the CTS hands can be quantified by measuring skin capacitance. Methods. Patients with clinical and electrophysiological signs of idiopathic carpal tunnel syndrome meeting the inclusion criteria were recruited. The patients were also scored based on the Brigham carpal tunnel severity score. Skin capacitance was measured using Corneometer CM825 (C&K Electronic, GmbH). The measurements were taken from the palmar aspect of distal phalanx of the index and little finger of the affected hand. Normal healthy patients with no signs and symptoms of carpal tunnel syndrome were recruited as controls and skin capacitance was measured in a similar fashion as the CTS group. Results. The CTS group consisted of 25 patients (18 female & 7 male) and 35 hands with an average age of 59.2 years (33-83 years). The mean symptom severity score was 2.80 (1.27-4.18; SD 0.82) and functional status score was 2.53 (1-4.26; SD 1.08). The mean ratio of skin hydration between the index and little finger was 0.85 (0.6-1.25; SD 0.155). Using the paired t-test to determine paired differences between index and little finger measurements, the mean difference was 12.6 (p<0.001). The control group consisted of 15 people (9 female and 6 male) and 30 hands. The average age was 47.3 years. The mean ratio of skin hydration between the index and little finger was 0.97 (0.77-1.42 SD 0.105). Using the paired t-test to determine paired differences between index and little finger measurements, the mean difference was 1.31 (p=0.317). The difference in skin hydration between the index and little finger was directly compared between the controls and CTS group, this difference was statistically significant, p=0.002. Conclusion. A simple method to determine dysautonomia, using Corneometer CM825, by the clinician has been demonstrated. Measurement of skin capacitance will reduce the dependence on electrophysiological studies, thus reducing the time for arriving at a diagnosis, improved patient satisfaction and cost-effectiveness

Summary. Measurement of changes in the physiological cycle-to-cycle variability in gait kinematics using the ELLIS approach holds promise as a new tool for quantitative evaluation of gait adaptability. Introduction. Adaptability is arguably one of the most crucial factors of gait function. However, functional limitations in adaptability have not been well documented, presumably due to the inability to accurately measure this aspect. For this purpose, we developed a new method to quantify subtle changes in cycle-to-cycle physiological variability in gait kinematics; a technique designated as the entropy of leg-linkage inertial signals (ELLIS) analysis. A previous study (Tochigi et al., JOR 2012) found that the ELLIS outputs in an asymptomatic cohort) became lower with greater age, and that subjects with symptomatic knee osteoarthritis exhibited lower values compared to age-matched asymptomatic subjects. In addition, highly consistent speed-dependent increases in ELLIS outputs (in the asymptomatic subjects) were also documented. This speed-dependency is consistent with the fact that stable walking at a faster pace places higher demands on the neuromuscular control systems. Complex interactions across multiple controlling factors presumably increase perturbations to gait kinematics within the “normal” range (i.e., increase in physiological variability). To advance understanding of the degree of speed dependence, the present study aimed to test whether or not the ELLIS outputs would linearly increase with increase in walking speed. Methods. Six asymptomatic adult individuals (all males, age 24 – 47) were recruited and completed an institutionally approved consent process. No subjects had lower limb symptoms, histories of major lower limb pathology in the prior year, or systemic conditions that might affect gait (e.g., neurological or cardiovascular impairments). For leg kinematics measurement, each subject wore a portable wireless inertial monitor, which was strapped to the lateral aspect of the left or right calf, just above the ankle. Self-selected gait speed was determined during a timed corridor walk. Data during a treadmill walk were collected at 60%, 80%, 100%, 120% and 140% of the individuals’ self-selected pace, in a randomised order. The kinematic data collected were six channels of synchronised signals (sampling rate: 150Hz), including tri-axial rotational rate and tri-axial acceleration data. For each of these two 3-D kinematic datasets, entropy was measured individually using a non-linear measure designated as Sample Entropy (SampEn). These outputs were plotted for the relationship with relative speed change, and the correlation between entropy and relative speed change was tested using the Pearson's linear regression model. Results. The SampEn values of the rotational rate data exhibited high positive correlation with relative speed changes, as indicated by the correlation coefficients (r) > 0.95 in all subjects, while those for the acceleration data exhibited modest correlation (r: 0.66 to 0.99). Conclusion. These data support the hypothesised speed-dependent linear increase of ELLIS outputs. Assuming the sensitivity of this speed-dependent change is associated with the integrity of gait adaptability, this approach may be capable of quantifying decrease of gait adaptability in various pathological conditions. This gait analysis technique does not require elaborate laboratory equipment, permitting data collection at a variety of non-specialised settings, such as private clinics and community-based settings. The ELLIS approach holds promise as a new convenient diagnostic tool

Summary Statement. A biomimetic tissue engineering strategy involving culture on bone scaffolds in perfusion bioreactors allows the construction of stable, viable, patient-specific bone-like substitutes from human induced pluripotent stem cells. Introduction. Tissue engineering of viable bone substitutes represents a promising therapeutic strategy to mitigate the burden of bone deficiencies. Human induced pluripotent stem cells (hiPSCs) have an excellent proliferation and differentiation capacity, and represent an unprecedented resource for engineering of autologous tissue grafts, as well as advanced tissue models for biological studies and drug discovery. A major challenge is to reproducibly expand, differentiate and organize hiPSCs into mature, stable tissue structures. Based on previous studies (1,2,3), we hypothesised that the culture conditions supporting bone tissue formation from adult human mesenchymal stem cells (hMSCs) and human embryonic stem cell (hESC)-derived mesenchymal progenitors could be translated to hiPSC-derived mesenchymal progenitors. Our objectives were to: 1. Derive and characterise mesenchymal progenitors from hiPSC lines. 2. Engineer bone substitutes from progenitor lines exhibiting osteogenic potential in an osteoconductive scaffold – perfusion bioreactor culture model. 3. Assess the molecular changes associated with the culture of hiPSC-progenitors in perfusion bioreactors, and evaluate the stability of engineered bone tissue substitutes in vivo. Methods. hESC and hiPSC lines (derived using retroviral vectors, Sendai virus and episomal vectors) were karyotyped, characterised for pluripotency and induced into the mesenchymal lineage. Mesenchymal progenitors were evaluated for growth potential, expression of surface markers and differentiation potential. Progenitors exhibiting osteogenic potential were cultured on decellularised bovine bone scaffolds in perfusion bioreactors for 5 weeks as previously (3). Global gene expression profiles were evaluated prior and after bioreactor culture. Bone development was investigated using biochemical and histological methods, and by micro-computed tomography (μCT) imaging over the duration of bioreactor culture and after 12-week subcutaneous implantation in immunodeficient mice. Results. Progenitors with high proliferation potential, expressing typical mesenchymal surface antigens were successfully derived from three hiPSC lines. Differences in mesenchymal surface antigens expression and global gene expression profiles of progenitors from different lines corresponded to their differentiation abilities toward the osteogenic, chondrogenic and adipogenic lineages. Bioreactor culture yielded constructs with significantly higher cellularity, AP activity and osteopontin release into the culture medium as compared to static culture. Dense bone matrix formation was evidenced by the positive staining of collagen, osteopontin, bone sialoprotein and osteocalcin. In comparison, static culture yielded constructs with uniformly distributed cells, however tissue formation was scarce. μCT revealed a significant increase in bone structural parameters, evidencing mineralization of the deposited bone tissue during the 5-week culture in bioreactors. Osteogenesis and bone tissue formation were comparable between hESCs, hiPSCs and hMSCs (3). Bioreactor cultivation resulted in repression of genes involved in proliferation and tumorigenesis, and upregulation of genes associated with osteogenesis and bone development. Engineered bone tissue displayed stable phenotype after 12-week implantation in vivo, with cells of human origin, ingrowing vasculature and osteoclasts, suggesting an initiation of tissue remodeling. Discussion/Conclusion. Our biomimetic strategy opens the possibility to construct an unlimited quantity of patient-specific bone grafts for personalised applications, and to generate qualified experimental models to study bone biology under normal and pathological conditions, as well as test new drugs using selected pools of hiPSC lines

Summary. From a large 3D Caucasian bone data base, female population had significantly larger acetabular anatomical anteversion angle and combined acetabular-femoral anteversion angle than that of male population. There was no significant difference in femoral neck anteversion angles between the groups. Introduction. Combined Anteversion (CA) angle of acetabular component and femoral neck is an important parameter for a successful Total Hip Arthroplasty (THA). The purpose of this study was to electronically measure the version angles of native acetabulum and femur in matured normal Caucasian population from large 3D CT data base. Our question was if there was any significant difference in CA between male and female population. Methods. 221 anonymous (134 males and 87 females) CT paired pelvic and femoral scans from normal Caucasian population with age range of 30–93 years old were analyzed. CT data was converted to virtual bones using custom CT analytical software. 1. (SOMA. TM. V.3.2). Acetabular Anatomical Anteversion (AA) angle as defined by Murray. 2. was selected. The acetabular rim plane was constructed by selecting 3 bony land marks from pubis, ilium and ischium. The AA was measured against pelvic frontal plane. Femoral neck Anteversion (FA) was measured between neck axis plane and the Coronal plane which was defined by posterior condyles. The neck axis plane was defined as being the plane passing through femoral neck axis and being perpendicular to the transverse plane which is defined by distal femoral condyles. The CA angle in standing position was computed as the summation of AA and FNA angles. All the measurements were performed for total, male and female populations. Student's t tests were performed to compare gender difference with an assumed 95% confidence level. The relationship between AA and FA for each gender was studied by the plot of AA and a function of FA. Results. The mean AA angle for total population was 25.8°, SD=6.52°. (male 24.8°, SD=5.91°, female was 27.3°, SD=7.12°. P=0.006). The mean FA angle for total population was 14.3°, SD=7.95°. (male 13.4°, SD=7.99°, female 15.6°, SD=7.76°. P=0.051). The mean CA angle for total population was 40.1°, SD=10.76°. (male 38.2° SD= 10.38 °, female 42.9° SD= 10.79 °. P=.0002). The plot of AA as a function FA is shown. The frequency distribution of CA angle is plotted for males and females. Discussion/Conclusion. The results showed both AA and CA angles were significantly smaller in the male than that in female. However there was no significant difference in FA between male and female. The plot of AA as a function of FA showed no correlation (R. 2. <.09) between the two angles for both male (R. 2. =.0097) and female (R. 2. =.0029). The FA angle of a femoral stem implant in THA may be smaller than that of natural femur, therefore a higher AA or higher posterior build up may be required for the acetabular component to achieve optimal function of a THA. This may be a more significant issue in female population. The limitations of this study was that this population did not have pathological conditions which could lead to THA. However, it should provide reference guidance comparing normal anatomy between male and female

Objectives

Given the function of adiponectin (ADIPOQ) on the inflammatory condition of obesity and osteoarthritis (OA), we hypothesized that the ADIPOQ gene might be a candidate gene for a marker of susceptibility to OA.

Objectives

The aim of this study was to investigate the effect of hyperglycaemia on oxidative stress markers and inflammatory and matrix gene expression within tendons of normal and diabetic rats and to give insights into the processes involved in tendinopathy.

Objectives

This study looked to analyse the expression levels of microRNA-140-3p and microRNA-140-5p in synovial fluid, and their correlations to the severity of disease regarding knee osteoarthritis (OA).

Objectives

Osteoarthritis (OA) is characterised by articular cartilage degradation. MicroRNAs (miRNAs) have been identified in the development of OA. The purpose of our study was to explore the functional role and underlying mechanism of miR-138-5p in interleukin-1 beta (IL-1β)-induced extracellular matrix (ECM) degradation of OA cartilage.

Objectives

To review the current best surgical practice and detail a multi-disciplinary approach that could further reduce joint replacement infection.

Objectives

The need for bone tissue supplementation exists in a wide range of clinical conditions involving surgical reconstruction in limbs, the spine and skull. The bone supplementation materials currently used include autografts, allografts and inorganic matrix components; but these pose potentially serious side-effects. In particular the availability of the autografts is usually limited and their harvesting causes surgical morbidity. Therefore for the purpose of supplementation of autologous bone graft, we have developed a method for autologous extracorporeal bone generation.

Several experimental models have been used to produce intravascular fat embolism. We have developed a simple technique to induce fat embolism using corn oil emulsified with distilled water to form fatty micelles. Fat embolism was produced by intravenous administration of these fatty micelles in anaesthetised rats, causing alveolar oedema, haemorrhage and increased lung weight.

Histopathological examination revealed fatty droplets and fibrin thrombi in the lung, kidney and brain. The arteriolar lumen was filled with fatty deposits. Following fat embolism, hypoxia and hypercapnia occurred. The plasma phospholipase A₂, nitrate/nitrite, methylguidanidine and proinflammatory cytokines were significantly increased. Mass spectrometry showed that the main ingredient of corn oil was oleic acid.

This simple technique may be applied as a new animal model for the investigation of the mechanisms involved in the fat embolism syndrome.