174 research outputs found

    Introduction

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    The concept of Responsible Research and Innovation (RRI) originates in discourses on emerging technologies and research ethics in contested innovative fields, such as nanotechnologies or geo-engineering, and has been predominantly driven by European research and innovation policy over the past 10 years. The concept was initially developed and introduced by policy makers and social scientists, but recent studies have aimed to shed light on the implementation of responsible research and innovation practices in business. The contributions collected in this book are a result of work conducted by seven partner organisations in the European funded Horizon 2020 project "COMPASS – Evidence and opportunities for responsible innovation in SMEs". In combination, they illustrate that responsible innovation (RI) has been emerging as a new field in the ongoing discourse on the role and responsibility of business in society

    Expression of matrix metalloproteinase-1 (MMP-1) in Wistar rat's intervertebral disc after experimentally induced scoliotic deformity

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    <p>Abstract</p> <p>Introduction</p> <p>A scoliotic deformity on intervertebral discs may accelerate degeneration at a molecular level with the production of metalloproteinases (MMPs). In the present experimental study we evaluated the presence of MMP-1 immunohistochemically after application of asymmetric forces in a rat intervertebral disc and the impact of the degree of the deformity on MMP-1 expression.</p> <p>Material-Method</p> <p>Thirty female Wistar rats (aged 2 months old, weighted 200 ± 10 grams) were used. All animals were age, weight and height matched. A mini Ilizarov external fixator was applied at the base of a rat tail under anaesthesia in order to create a scoliotic deformity of the intervertebral disc between the 9<sup>th </sup>and 10<sup>th </sup>vertebrae. Rats were divided into three groups according to the degree of the deformity. In group I, the deformity was 10°, in group II 30° and in group III 50°. The rats were killed 35 days after surgery. The discs were removed along with the neighbouring vertebral bodies, prepared histologically and stained immunohistochemically. Immunopositivity of disc's cells for MMP-1 was determined using a semi-quantitative scored system.</p> <p>Results</p> <p>MMP-1 immunopositivity was detected in disc cells of annulus fibrosus of all intervertebral disc specimens examined. The percentage of MMP-1 positive disc cells in annulus fibrosus in group I, II and III were 20%, 43% and 75%, respectively. MMP-1 positivity was significantly correlated with the degree of the deformity (p < 0,001). An increase of chondrocyte-like disc cells was observed in the outer annulus fibrosus and at the margin of the intervertebral disc adjacent to the vertebral end plates. The difference in the proportion of MMP-1 positive disc cells between the convex and the concave side was statistically not significant in group I (p = 0,6), in group II this difference was statistically significant (p < 0,01). In group III the concave side showed a remarkable reduction in the number of disc's cells and a severe degeneration of matrix microstructure.</p> <p>Conclusion</p> <p>The present study showed that an experimentally induced scoliotic deformity on a rat tail intervertebral disc results in over-expression of MMP-1, which is dependent on the degree of the deformity and follows a dissimilar distribution between the convex and the concave side.</p

    The Effect of Sustained Compression on Oxygen Metabolic Transport in the Intervertebral Disc Decreases with Degenerative Changes

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    Intervertebral disc metabolic transport is essential to the functional spine and provides the cells with the nutrients necessary to tissue maintenance. Disc degenerative changes alter the tissue mechanics, but interactions between mechanical loading and disc transport are still an open issue. A poromechanical finite element model of the human disc was coupled with oxygen and lactate transport models. Deformations and fluid flow were linked to transport predictions by including strain-dependent diffusion and advection. The two solute transport models were also coupled to account for cell metabolism. With this approach, the relevance of metabolic and mechano-transport couplings were assessed in the healthy disc under loading-recovery daily compression. Disc height, cell density and material degenerative changes were parametrically simulated to study their influence on the calculated solute concentrations. The effects of load frequency and amplitude were also studied in the healthy disc by considering short periods of cyclic compression. Results indicate that external loads influence the oxygen and lactate regional distributions within the disc when large volume changes modify diffusion distances and diffusivities, especially when healthy disc properties are simulated. Advection was negligible under both sustained and cyclic compression. Simulating degeneration, mechanical changes inhibited the mechanical effect on transport while disc height, fluid content, nucleus pressure and overall cell density reductions affected significantly transport predictions. For the healthy disc, nutrient concentration patterns depended mostly on the time of sustained compression and recovery. The relevant effect of cell density on the metabolic transport indicates the disturbance of cell number as a possible onset for disc degeneration via alteration of the metabolic balance. Results also suggest that healthy disc properties have a positive effect of loading on metabolic transport. Such relation, relevant to the maintenance of the tissue functional composition, would therefore link disc function with disc nutrition

    Biomechanical evaluation of predictive parameters of progression in adolescent isthmic spondylolisthesis: a computer modeling and simulation study

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    <p>Abstract</p> <p>Background</p> <p>Pelvic incidence, sacral slope and slip percentage have been shown to be important predicting factors for assessing the risk of progression of low- and high-grade spondylolisthesis. Biomechanical factors, which affect the stress distribution and the mechanisms involved in the vertebral slippage, may also influence the risk of progression, but they are still not well known. The objective was to biomechanically evaluate how geometric sacral parameters influence shear and normal stress at the lumbosacral junction in spondylolisthesis.</p> <p>Methods</p> <p>A finite element model of a low-grade L5-S1 spondylolisthesis was constructed, including the morphology of the spine, pelvis and rib cage based on measurements from biplanar radiographs of a patient. Variations provided on this model aimed to study the effects on low grade spondylolisthesis as well as reproduce high grade spondylolisthesis. Normal and shear stresses at the lumbosacral junction were analyzed under various pelvic incidences, sacral slopes and slip percentages. Their influence on progression risk was statistically analyzed using a one-way analysis of variance.</p> <p>Results</p> <p>Stresses were mainly concentrated on the growth plate of S1, on the intervertebral disc of L5-S1, and ahead the sacral dome for low grade spondylolisthesis. For high grade spondylolisthesis, more important compression and shear stresses were seen in the anterior part of the growth plate and disc as compared to the lateral and posterior areas. Stress magnitudes over this area increased with slip percentage, sacral slope and pelvic incidence. Strong correlations were found between pelvic incidence and the resulting compression and shear stresses in the growth plate and intervertebral disc at the L5-S1 junction.</p> <p>Conclusions</p> <p>Progression of the slippage is mostly affected by a movement and an increase of stresses at the lumbosacral junction in accordance with spino-pelvic parameters. The statistical results provide evidence that pelvic incidence is a predictive parameter to determine progression in isthmic spondylolisthesis.</p

    Simulated-Physiological Loading Conditions Preserve Biological and Mechanical Properties of Caprine Lumbar Intervertebral Discs in Ex Vivo Culture

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    Low-back pain (LBP) is a common medical complaint and associated with high societal costs. Degeneration of the intervertebral disc (IVD) is assumed to be an important causal factor of LBP. IVDs are continuously mechanically loaded and both positive and negative effects have been attributed to different loading conditions

    Current strategies for treatment of intervertebral disc degeneration: substitution and regeneration possibilities

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    Background: Intervertebral disc degeneration has an annual worldwide socioeconomic impact masked as low back pain of over 70 billion euros. This disease has a high prevalence over the working age class, which raises the socioeconomic impact over the years. Acute physical trauma or prolonged intervertebral disc mistreatment triggers a biochemical negative tendency of catabolic-anabolic balance that progress to a chronic degeneration disease. Current biomedical treatments are not only ineffective in the long-run, but can also cause degeneration to spread to adjacent intervertebral discs. Regenerative strategies are desperately needed in the clinics, such as: minimal invasive nucleus pulposus or annulus fibrosus treatments, total disc replacement, and cartilaginous endplates decalcification. Main Body: Herein, it is reviewed the state-of-the-art of intervertebral disc regeneration strategies from the perspective of cells, scaffolds, or constructs, including both popular and unique tissue engineering approaches. The premises for cell type and origin selection or even absence of cells is being explored. Choice of several raw materials and scaffold fabrication methods are evaluated. Extensive studies have been developed for fully regeneration of the annulus fibrosus and nucleus pulposus, together or separately, with a long set of different rationales already reported. Recent works show promising biomaterials and processing methods applied to intervertebral disc substitutive or regenerative strategies. Facing the abundance of studies presented in the literature aiming intervertebral disc regeneration it is interesting to observe how cartilaginous endplates have been extensively neglected, being this a major source of nutrients and water supply for the whole disc. Conclusion: Severalinnovative avenues for tackling intervertebral disc degeneration are being reported â from acellular to cellular approaches, but the cartilaginous endplates regeneration strategies remain unaddressed. Interestingly, patient-specific approaches show great promise in respecting patient anatomy and thus allow quicker translation to the clinics in the near future.The authors would like to acknowledge the support provided by the Portuguese Foundation for Science and Technology (FCT) through the project EPIDisc (UTAP-EXPL/BBBECT/0050/2014), funded in the Framework of the “International Collaboratory for Emerging Technologies, CoLab”, UT Austin|Portugal Program. The FCT distinctions attributed to J. Miguel Oliveira (IF/00423/2012 and IF/01285/ 2015) and J. Silva-Correia (IF/00115/2015) under the Investigator FCT program are also greatly acknowledged.info:eu-repo/semantics/publishedVersio

    Compact Polyelectrolyte Complexes: “Saloplastic” Candidates for Biomaterials

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    Precipitates of polyelectrolyte complexes were transformed into rugged shapes suitable for bioimplants by ultracentrifugation in the presence of high salt concentration. Salt ions dope the complex, creating a softer material with viscous fluid-like properties. Complexes that were compacted under the centrifugal field (CoPECs) were made from poly(diallyldimethyl ammonium), PDADMA, as polycation, and poly(styrene sulfonate), PSS, or poly(methacrylic acid), PMAA, as polyanion. Dynamic mechanical testing revealed a rubbery plateau at lower frequencies for PSS/PDADMA with moduli that decreased with increasing salt concentration, as internal ion pair cross-links were broken. CoPECs had significantly lower modulii compared to similar polyelectrolyte complexes prepared by the “multilayering ” method. The difference in mechanical properties was ascribed to higher water content (located in micropores) for the former and, more importantly, to their nonstoichiometric polymer composition. The modulus of PMAA/PDADMA CoPECs, under physiological conditions, demonstrated dynamic mechanical properties that were close to those of the nucleus pulposus in an intervertebral disk
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