Aim. The aim of the study was to define the peculiarities of bone remodeling and identify specific parameters to development to heterotopic ossification. Materials and methods. Markers of bone formation (Osteocalcin, serum type 1 procollagen (N-terminal) (tP1NP)) and bone resorption (serum collagen type 1 cross-linked C-telopeptide (β-CTx)) were determined by the electrochemiluminiscence immunoassay “ECLIA” for Elecsys user cobas immunoassay analyser. In the study were included 23 patients with spinal cord injury – first group (average age 26.8 ± 3.9, duration of spinal cord injury from 3 to 12 months) and 23 healthy people's appropriate age and gender (average age 30.6 ± 6.0, years). In the first group included 11 patients with spinal cord injury with the presence of heterotopic ossification – subgroup I and 12 patients with spinal cord injury without heterotopic ossification – subgroup II. Results. The results of examination showed that patients of first group had significantly higher bone markers than control group: P1NP (256.7±48.2 ng/ml vs 49.3±5.1 ng/ml, p<0.001), serum β-CTx (1.47±0.23 ng/ml vs 0.45±0.04 ng/ml, p<0.0001), osteocalcin (52.2±9.8 ng/ml vs 24.9±2.08 ng/ml, p<0.001). There were obtained that levels of bone remodeling markers in patients with HO were significantly higher in comparison with patients without HO: P1NP (404.9±84.9 ng/ml vs 133.2±15.7 ng/ml, p<0.001), serum β-CTx (1.75±0.23 ng/ml vs 0.28±0.14 ng/ml, p<0.0001), osteocalcin (87.1±18.9 ng/ml vs 29.4±3.7 ng/ml, p<0.001). Conclusion. The bone formation and bone resorption markers in patient of first group were significantly higher than in healthy individuals of appropriate age. The rate of bone turnover markers in patient with HO was considerably higher than in patient without HO and the process of formation dominated over the resorption in patient with HO

Summary Statement. In this study, we observed that MR16-1, an interleukin-6 inhibitor, recovered phosphatidylcholine containing docosahexaenoic acid at the injury site after spinal cord injury in mice model by using imaging mass spectrometry. Introduction. The current drugs for improving motor function of the limbs lost due to spinal cord injury (SCI) are ineffective. Development of new drugs for spinal cord injury is desired. MR16-1, an interleukin-6 inhibitor, is found to be effective in improving motor function after spinal cord injury in mice model. Thus, we examined the molecular mechanism in more detail. Therefore, the purpose of this study was to analyze the molecular changes in the spinal cord of the SCI mice treated with MR16-1 using imaging mass spectrometry. Methods. All experiments were performed according to the guidelines for animal experimentation and care and use of laboratory animals established by Hamamatsu University School of Medicine (Shizuoka, Japan). We used 36 adult female C57BL/6J mice for laminectomy and contusion injury of the spinal cord that were performed at the T10 level using the Infinite Horizon Impactor (IH Impactor, 60 kdyn; Muromachi, Tokyo, Japan). Immediately after SCI, mice were intraperitoneally injected with a single dose of MR16-1 (Chugai, Tokyo Japan) (100 µg/g body weight, MR16-1 group) or a single dose of phosphate-buffered saline (PBS) of the same volume (control group). Motor function of the hind limbs was evaluated using the Basso Mouse Scale (BMS), an open-field locomotor test in which the scores range from 0 points (scored for no ankle movement) to 9 points (scored for complete functional recovery). BMS scores were recorded at 1, 7, 14, 21, 28, 35, and 42 days after SCI. The spinal cord tissues were flash frozen and were sliced to a thickness of 8 µm using a cryostat (CM1950; Leica, Wetzler, Germany). Imaging mass spectrometry was used to visualise 12 molecular species of phosphatidylcholine (PC) from thin slices of the spinal cords obtained at 7 days post-SCI. Results. The contusive SCI immediately resulted in complete paralysis. The MR16-1–treated group showed a significant improvement in the BMS locomotor score compared with the control group at both 7 days and 42 days after SCI (1.4 vs 0.2 points and 4.0 vs 1.4 points, respectively). Phospholipids at 7 days after SCI showed unique distribution patterns. In particular, PCs containing docosahexaenoic acid (DHA) localised in the gray matter region was significantly higher in the MR16-1–treated group than in the control group, at 7 days post-SCI. Discussion. MR16-1 treatment showed to improve locomotor BMS score after 7 days of SCI compared with that observed in the control group. Spinal cord injury had induced inflammation; injury sites showed changes in the lipid content. We had previously reported that PC containing DHA mostly expressed in neuron cells decrease on injury sites. In this study, we observed that MR16-1 recovered PC containing DHA at the injury site. This may be associated with the recovery of motor function

Silver nanoparticles (AgNPs) possess anti-inflammatory activities and have been widely deployed for promoting tissue repair. Here we explored the efficacy of AgNPs on functional recovery after spinal cord injury (SCI). Our data indicated that, in a SCI rat model, local AgNPs delivery could significantly recover locomotor function and exert neuroprotection through reducing of pro-inflammatory M1 survival. Furthermore, in comparison with Raw 264.7-derived M0 and M2, a higher level of AgNPs uptake and more pronounced cytotoxicity were detected in M1. RNA-seq analysis revealed the apoptotic genes in M1 were upregulated by AgNPs, whereas in M0 and M2, pro-apoptotic genes were downregulated and PI3k-Akt pathway signaling pathway was upregulated. Moreover, AgNPs treatment preferentially reduced cell viability of human monocyte-derived M1 comparing to M2, supporting its effect on M1 in human. Overall, our findings reveal AgNPs could suppress M1 activity and imply its therapeutic potential in promoting post-SCI motor recovery

Summary Statement. Collagen scaffolds modified with collagen-binding bFGF promotes the neural regeneration in the rat hemisected spinal cord injury model. Objective. To investigate the effects of the collagen scaffolds (CS) combined with collagen-binding basic fibroblast growth factor (CBD-bFGF) on the neural recovery after spinal cord injury (SCI). Methods. The left lateral 3 mm hemisection SCI of rat model (at T9 level) was made. A bundle of 2mm×2mm×3mm CS fused with CBD-bFGF (2μg/10μl/bundle, CS/bFGF) was implanted into hemi-transected gap. There were four groups in this experiment, the sham group without SCI, the control group with SCI, the CS-treated group with SCI and implanted CS, the CS/bFGF-treated group with SCI and implanted CS/bFGF. The 21-point Basso-Beattie-Bresnahan (BBB) scale was performed before the operation and at 1 week intervals after SCI for 8 weeks to assess the hindlimb locomotor function. 4 and 8 weeks after operation, footprint analysis was applied to evaluate the body weight support and limb coordination, respectively. H&E staining and immunohistochemistry for neurofilament (NF) and glial fibrillary acidic protein (GFAP) was administrated for histological evaluation at 4 and 8 weeks post injury, respectively. Results. 1). The survival curve showed that CS/bFGF-treated group had a significantly higher survival rate than that of the control group and CS-treated group, while the control group had the lowest one. 2). BBB score showed all the animals with SCI showed a gradual recovery in hindlimb locomotor function during the 8 weeks period. Moreover, the left hindlimb function in CS/bFGF-treated recovered faster and better than that of the control group and CS-treated group. Footprint analysis showed a significant improvement in interlimb coordination in the CS/bFGF-treated group contrast to the CS-treated and control groups at 4 and 8 weeks, respectively. The base of support was obviously reduced in CS/bFGF group and 8 weeks after SCI, the base of support of the CS/bFGF-treated group could closely approximate that of sham-operated group. Compared to the control and CS-treated groups, the CS/bFGF-treated group showed smaller angle of rotation. In addition, toe dragging was more serious in the control and CS-treated group than that in the CS/bFGF group. 3). At 4 and 8 weeks, spinal cord sections stained with H&E showed a significant increase in the density of linear fibrous tissues and cell infiltration in and around the scaffold of CS/bFGF-treated group compared to the control and CS-treated groups. The CS/bFGF-treated group showed highest NF-positive neural fiber density. Besides, the NF-positive neural fibers could extend into the scaffold and grow along with the direction of CS. GFAP. +. astrocytes were present around the hemi-transected site in all SCI rats. But the CS/bFGF-treated group showed lower number of GFAP. +. cells than that of the control and CS treated group at 4 and 8 weeks after the surgery, respectively, while in the control group the number of GFAP+ cells was highest. Conclusions. The data suggested that implantation of CS/bFGF into a semi-transected SCI rat model can guide axon growth at the injury site and promote obvious improvement in functional recovery. As a result, CS/bFGF combination could be a promising alternative system for the clinical application of SCI repair

Spinal cord injury (SCI) is a devastating disorder for which the identification of exacerbating factors is urgently needed. Although age, blood pressure and infection are each considered to be prognostic factors in patients with SCI, exacerbating factors that are amenable to treatment remain to be elucidated. Microglial cells, the resident immune cell in the CNS, form the first line of defense after being stimulated by exposure to invading pathogens or tissue injury. Immediately after SCI, activated microglia enhance and propagate the subsequent inflammatory response by expressing cytokines, such as TNF-α, IL-6 and IL-1β. Recently, we demonstrated that the activation of microglia is associated with the neuropathological outcomes of SCI. Although the precise mechanisms of microglial activation remain elusive, several basic research studies have reported that hyperglycemia is involved in the activation of resident monocytic cells, including microglia. Because microglial activation is associated with secondary injury after SCI, we hypothesized that hyperglycemia may also influence the pathophysiology of SCI by altering microglial responses. The mice were anesthetized with pentobarbital (75 mg/kg i.p.) and were subjected to a contusion injury (70 kdyn) at the 10th thoracic level using an Infinite Horizons Impactor (Precision Systems Instrumentation). For flow cytometry, the samples were stained with the antibodiesand analyzed using a FACS Aria II flow cytometer and the FACSDiva software program (BD Biosciences). We retrospectively identified 528 SCI patients admitted to the Department of Orthopaedic Surgery at the Spinal Injuries Center (Fukuoka, Japan) between June 2005 and May 2011. The patients' data were obtained from their charts. We demonstrate that transient hyperglycemia during acute SCI is a detrimental factor that impairs functional improvement in mice and human patients after acute SCI. Under hyperglycemic conditions, both in vivo and in vitro, inflammation was enhanced through promotion of the nuclear translocation of the nuclear factor kB (NF-kB) transcription factor in microglial cells. During acute SCI, hyperglycemic mice exhibited progressive neural damage, with more severe motor deficits than those observed in normoglycemic mice. Consistent with the animal study findings, a Pearson χ2 analysis of data for 528 patients with SCI indicated that hyperglycemia on admission (glucose concentration ≥126 mg/dl) was a significant risk predictor of poor functional outcome. Moreover, a multiple linear regression analysis showed hyperglycemia at admission to be a powerful independent risk factor for a poor motor outcome, even after excluding patients with diabetes mellitus with chronic hyperglycemia (regression coefficient, −1.37; 95% confidence interval, −2.65 to −0.10; P < 0.05). Manipulating blood glucose during acute SCI in hyperglycemic mice rescued the exacerbation of pathophysiology and improved motor functional outcomes. Our findings suggest that hyperglycemia during acute SCI may be a useful prognostic factor with a negative impact on motor function, highlighting the importance of achieving tight glycemic control after central nervous system injury

Summary Statement. The mechanism of spinal cord injury varies across the human population and this may be important for the development of effective therapies. Therefore, detailed understanding of how variables such as impact velocity and depth affect cord tissue damage is important. Introduction. Studies have shown an independent effect of impact velocity and depth on injury severity, thereby suggesting importance of the interaction between the two for spinal cord injury. This work examines both the individual and interactive effects of impact velocity and impact depth on demyelination, tissue sparing, and behavioural outcomes in the rat cervical spinal cord. It also aims to understand the contribution of the energy applied during impact, not only the impact factors. Decoupling the effects of these two impact parameters will help to describe the injury mechanism. Maximum principal strain has also been shown to be useful as a predictor for neural tissue damage in vivo and in finite element (FE) models. A better understanding of this relationship with experimental results may help to elucidate the mechanics of spinal cord injury. Methods. In this study, 54 male Sprague-Dawley rats were given a contusion spinal cord injury at impact speeds of 8 mm/s, 80 mm/s, or 800 mm/s with depths of 0.9 mm or 1.5 mm. Animals recovered for 7 days followed by behavioural assessment and examination of the spinal cord tissue for demyelination and tissue sparing at 1 mm intervals, ±3 mm rostrocaudally to the epicentre. In parallel, a previously developed finite element model of the rat spinal cord was used to examine the resulting maximum principal strains in the spinal cord for correlations with histological and mechanical impact data. Results and discussion. Impact depth was a consistent factor in predicting axonal damage, tissue sparing, and the resulting behavioural deficit. Increased impact velocity resulted in significantly higher impact energies and measureable tissue damage at the 1.5 mm impact depth, but not at the 0.9 mm impact depth and is best displayed by the percentage of axon damage at the injury epicentre. Linear correlation analysis with FEA strain showed significant (p≪0.001) correlations with axonal damage in the ventral (R2=0.86) and lateral (R2=0.74) regions of the spinal cord and with white matter (R2=0.90) and grey matter (R2=0.76) sparing. Discussion and Conclusion. The difference in injury severity to velocity at different impact depths identifies the existence of threshold interactions between the two impact factors. Beyond this point incremental increases in either velocity or depth are more likely to result in significantly increased impact energy and thus tissue damage and functional impairment. The relationship between the impact depth and velocity of injury demonstrated a more rate sensitive response to spinal cord tissue damage at the deep (1.5 mm) impact depth than at the shallow (0.9 mm) impact depth. Impact velocity also became quickly less significant than impact depth in determining tissue damage further from the epicentre. Furthermore, the results shown by this work extend the research identifying significant correlations between maximum principal strain and neurological tissue damage

The inability to replace human muscle in surgical practice is a significant challenge. An artificial muscle controlled by the nervous system is considered a potential solution for this. We defined it as neuromuscular prosthesis. Muscle loss and dysfunction related to musculoskeletal oncological impairments, neuromuscular diseases, trauma or spinal cord injuries can be treated through artificial muscle implantation. At present, the use of dielectric elastomer actuators working as capacitors appears a promising option. Acrylic or silicone elastomers with carbon nanotubes functioning as the electrode achieve mechanical performances similar to human muscle in vitro. However, mechanical, electrical, and biological issues have prevented clinical application to date. In this study, materials and mechatronic solutions are presented which can tackle current clinical problems associated with implanting an artificial muscle controlled by the nervous system. Progress depends on the improvement of the actuation properties of the elastomer, seamless or wireless integration between the nervous system and the artificial muscle, and on reducing the foreign body response. It is believed that by combining the mechanical, electrical, and biological solutions proposed here, an artificial neuromuscular prosthesis may be a reality in surgical practice in the near future

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

Summary Statement. Spinal cord injury is characterised by an inflammatory cascade that leads to neuronal death by neurotoxicity. In a model of spinal cord damage we successfully preserved the number of ventral horn neurons by treatment with interleukin-1 receptor antagonist (IL1RA) and neurotrophin (NT)-3. Introduction. Secondary damage after spinal cord injury (SCI) is characterised by activation of microglial cells that release neurotoxic agents. This results in apoptotic death of neurons that survived the initial trauma. Interleukin (IL)-1 is one of the most prominent mediators of neurotoxicity. Organotypic spinal cord slice cultures (OSCSC) are a useful in vitro model of spinal cord injury. We have previously shown that OSCSC degenerate substantially during in vitro incubation under standard conditions. Our aim was to treat OSCSC with the putatively neuroprotective agents IL-1 receptor antagonist (IL1RA) and neurotrophin (NT)-3 and to evaluate neuronal and microglial populations as well as axonal preservation. We hypothesised that treatment with the above substances would enhance neuronal survival and suppress microglial activation. Materials & Methods. OSCSC were obtained from p9 (p=postnatal) mice and cultured in a 3-D collagen matrix for 0, 2, 4, 6 and 8 days in vitro (div). Neuroprotective substances were added to culture media, resulting in 4 treatment groups: IL1RA, NT3, IL1RA+NT3, and control (only medium). After fixation cultures were stained immunohistochemically for the neuronal marker NeuN and α-neurofilament (NF-L). Microglial cells were marked with isolectin B. 4. (IB. 4. ). Neurons in the ventral and dorsal horns were counted manually. The number of resting and activated microglial cells was calculated within the white and grey matter based on staining intensity and circularity index. Axonal preservation was evaluated qualitatively. Results. OSCSC under control conditions showed signs of early degeneration after 2 div with decreased number of neurons within both the ventral and dorsal horns. However, significant differences between the groups were noted after 8 div: In the ventral horns, the neurons in all treatment groups were significantly more numerous compared to the control group. In the IL1RA+NT3 group the number of neurons did not differ significantly when compared to directly fixed cultures (div 0), whereas that number was significantly decreased in the other groups. After 8 div the number of activated microglial cells was significantly increased in the control group compared to all treatment groups both in the white and grey matter. Qualitative analysis of axonal preservation after 6 and 8 div revealed axonal sprouting within the white matter in all groups. However, these sprouting axons seemed to expand into the collagen matrix only in the three treatment groups. Discussion/Conclusion. We demonstrate a neuroprotective effect of IL1RA and NT3 in OSCSC. OSCSC normally degenerate after in vitro incubation, however neurons in the ventral horns are sustained at initial levels in the IL1RA+NT3 group. At the same time microglial activation is suppressed in all treatment groups compared to controls. Finally, treatment of OSCSC with IL1RA and NT3 seem to be associated with axonal sprouting outside the cultures

Summary Statement. The spinal cord showed marked sensibility to acute compression causing complete and irreversible injury. On the contrary, the spinal cord has more ability for adaptation to slow progressive compression mechanisms having the possibility of neural recovery after compression release. Introduction. The aim of this experimental study was to establish, by means of neurophysiologic monitoring, the degree of compression needed to cause neurologic injury to the spinal cord, and analyze whether these limits are different making fast or slow compression. Material and Methods. Spinal cord was exposed from T7 to T11 in 5 domestic pigs with a mean weight of 35 kg. The T8 and T9 spinal roots were also exposed. A pair of sticks, attached to a precise compression device, was set up to both sides of the spinal cord between T8 and T9 roots. Sequentially, the sticks were approximated 0.5 mm every 2 minutes causing progressive spinal cord compression. An acute compression of the spinal cord was also reproduced by a 2.5 mm displacement of the sticks. Cord to cord motor evoked potentials were obtained with two epidural catheters, stimulating proximal to T6 and recording below the compression level, distal to T10, for each sequential approach of the sticks. Results. The mean width of the dural sac was 7.1 mm. For progressive compression, increasing latency and decreasing amplitude of the evoked potentials were observed after a mean displacement of the sticks of 3.2 ± 0.9 mm, the evoked potential finally disappearing after a mean displacement of 4.6 ± 1.2 mm. The potential returned 16.8 ± 3.2 minutes after the compression was stopped in every case. The evoked potentials immediately disappeared after an acute compression 2.5 ± 0.3 mm, without any sign of recovering after 30 minutes. Conclusion. The proposed experimental model replicates the mechanism of a spinal cord injury caused by medially displaced screws into the spinal canal, causing therefore lateral compression to the spinal cord. The spinal cord showed marked sensibility to acute compression, which caused complete and irreversible injury. On the contrary, the spinal cord has more ability for adaptation to progressive and slow compression mechanisms. From a clinical point of view, it seems mandatory to avoid maneuvers of rapid mobilization or acute, even minimal, contusions of the thoracic cord

Summary. Collagen scaffolds loaded with mesenchymal stem cells accelerate neurological recovery in rat spinal hemisection. Objective. To investigate the implantation effects of the collagen scaffold (CS) combined with mesenchymal stem cells (MSCs) on the function recovery of spinal cord injury (SCI) with a lateral hemisection SCI SD rat model. Methods. MSCs were prepared from SD rat bone marrow. A T9 hemisection SCI SD rat model was developed with the removal of a 3mm left hemicord segment and a bundle of 2mm×2mm×3mm CS loaded with MSCs (5×10. 5. cell/20μl/bundle, CS/MSC) was implanted into hemi-transected gap. Four groups were randomly divided: the sham group without SCI, the control group with SCI, the CS-treated group with SCI and implanted CS, the CS/MSC-treated group with SCI and implanted CS/MSC. The neurological function recovery was evaluated by the 21-point Basso-Beattie-Bresnahan (BBB) scale and footprint analysis before and after SCI. The histological evaluation was performed at 4 and 8 weeks post injury by H&E staining and immunohistochemistry for neurofilament (NF), glial fibrillary acidic protein (GFAP) and neuron-specific enolase (NES). Results. All the rats in the CS/MSC-treated group were alive while some rats were dead in the control and CS-treated groups. The BBB scores before the operation and at 1 week intervals after SCI for 8 weeks showed that the left hindlimbs function of CS/MSC-treated group restored faster and better than that of the control and CS-treated groups. In the ipsilateral hindlimb (left side), compared to the control and CS-treated group, the CS/MSC-treated group showed significant improvement in interlimb coordination by measuring the difference in stride length of fore- and hind-limb at 4 and 8 weeks, respectively. The base of support in CS/MSC-treated group was significantly reduced, and at 8 weeks, approximate equal to that of the sham group. The CS/MSC-treated group also showed smaller angle of rotation compared to the control and CS-treated groups. Histologically, compared to the control and CS-treated groups, spinal cord sections stained with H&E showed more tissue preservation in and around the injury site in the CS/MSC-treated group. Meanwhile, more NF-positive neural fibers, more density of NES staining and less GFAP positive astrocytes were observed in and around the injury site in the CS/MSC-treated group. Conclusions. These findings show that the combined application of CS and MSCs has an effect on neuroprotection and neurite guidance in the SCI rat model. It is well suggested the system would be an ideal approach to repair the spinal defect and to promote functional recovery after SCI

Near infrared light between the wavelengths of 700 and 950 nanometers has a relatively low absorption in tissue, and light of these wavelengths is able to penetrate several centimetres into tissue. Absorption of light is primarily due to hemoglobin. The absorption spectra for oxy-hemoglobin and deoxy-hemoglobin are different, and therefore comparison of light absorption at different wavelengths allows an assessment of the relative concentrations of these two chromophores. Light penetrates bone as well as soft-tissue, and near infrared spectroscopy (NIRS) is potentially a relatively simple, low-cost technique for assessing perfusion in bone. However, although absorption of light is low, scattering is high, and the spatial resolution of the measurement is poor. Application of the technique to the study of bone perfusion requires consideration of the potential confounding absorption arising from adjacent tissues that may have higher perfusion. A clinical problem of interest in our institute is that of vascular changes occurring in bone of patients with spinal cord injury (SCI), and the relationship of these changes to bone density changes. We have, therefore, concentrated on developing NIRS for measurement of the proximal tibia, which is a common site for fractures in these patients. In order to develop a probe for the measurement of bone, experiments were performed with phantoms containing infrared absorbing dyes. Numerical simulations were also performed using the Monte Carlo technique. One of the most important design considerations is the distance between the optode delivering light to the skin, and the collecting optode which detects light. It was found that a separation of 20 mm between the light source and detector was an optimum compromise for minimizing contributions from overlying skin and surrounding muscle, while still being able to detect light efficiently enough to measure dynamic changes in chromophore concentration. We have now started to apply this technique clinically. Relative changes of oxy- and deoxy-hemoglobin concentration have been measured in response to a range of interventions. Comparison has been made of the effect of different interventions designed to modify perfusion of bone (neuro-muscular stimulation of the calf, intermittent pneumatic compression, low amplitude high frequency vibration, and venous tourniquet). We are studying vascular reactivity in chronic SCI patients and controls and we have also started to investigate the effect of daily neuro-muscular stimulation in acute SCI patients. Preliminary results of these clinical studies will be presented

Objectives

Recent studies have shown that systemic injection of rapamycin can prevent the development of osteoarthritis (OA)-like changes in human chondrocytes and reduce the severity of experimental OA. However, the systemic injection of rapamycin leads to many side effects. The purpose of this study was to determine the effects of intra-articular injection of Torin 1, which as a specific inhibitor of mTOR which can cause induction of autophagy, is similar to rapamycin, on articular cartilage degeneration in a rabbit osteoarthritis model and to investigate the mechanism of Torin 1’s effects on experimental OA.

Trauma and orthopaedics is the largest of the surgical specialties and yet attracts a disproportionately small fraction of available national and international funding for health research. With the burden of musculoskeletal disease increasing, high-quality research is required to improve the evidence base for orthopaedic practice. Using the current research landscape in the United Kingdom as an example, but also addressing the international perspective, we highlight the issues surrounding poor levels of research funding in trauma and orthopaedics and indicate avenues for improving the impact and success of surgical musculoskeletal research.

Cite this article: Bone Joint J 2014; 96-B:1578–85.

Corticosteroids are prescribed for the treatment of many medical conditions and their adverse effects on bone, including steroid-associated osteoporosis and osteonecrosis, are well documented. Core decompression is performed to treat osteonecrosis, but the results are variable. As steroids may affect bone turnover, this study was designed to investigate bone healing within a bone tunnel after core decompression in an experimental model of steroid-associated osteonecrosis. A total of five 28-week-old New Zealand rabbits were used to establish a model of steroid-induced osteonecrosis and another five rabbits served as controls. Two weeks after the induction of osteonecrosis, core decompression was performed by creating a bone tunnel 3 mm in diameter in both distal femora of each rabbit in both the experimental osteonecrosis and control groups. An in vivo micro-CT scanner was used to monitor healing within the bone tunnel at four, eight and 12 weeks postoperatively. At week 12, the animals were killed for histological and biomechanical analysis.

In the osteonecrosis group all measurements of bone healing and maturation were lower compared with the control group. Impaired osteogenesis and remodelling within the bone tunnel was demonstrated in the steroid-induced osteonecrosis, accompanied by inferior mechanical properties of the bone.

We have confirmed impaired bone healing in a model of bone defects in rabbits with pulsed administration of corticosteroids. This finding may be important in the development of strategies for treatment to improve the prognosis of fracture healing or the repair of bone defects in patients receiving steroid treatment.