Search

Objectives: Bone marrow (BM) is increasingly getting into focus in the course of investigating pathomechanisms of adverse effects related to periprosthetic inflammation induced by local exposure to particles released from arthroplasty implants. Particles released from cobalt-chromium-molybdenum (CoCrMo) [for full text, please go to the a.m. URL]

Metallic implants are frequently used in medicine to support and replace degenerated tissues. Implant loosening due to particle exposure remains a major cause for revision arthroplasty. The exact role of metal debris in sterile peri‐implant inflammation is controversial, as it remains unclear whether and how metals chemically alter and potentially accumulate behind an insulating peri‐implant membrane, in the adjacent bone and bone marrow (BM). An intensively focused and bright synchrotron X‐ray beam allows for spatially resolving the multi‐elemental composition of peri‐implant tissues from patients undergoing revision surgery. In peri‐implant BM, particulate cobalt (Co) is exclusively co‐localized with chromium (Cr), non‐particulate Cr accumulates in the BM matrix. Particles consisting of Co and Cr contain less Co than bulk alloy, which indicates a pronounced dissolution capacity. Particulate titanium (Ti) is abundant in the BM and analyzed Ti nanoparticles predominantly consist of titanium dioxide in the anatase crystal phase. Co and Cr but not Ti integrate into peri‐implant bone trabeculae. The characteristic of Cr to accumulate in the intertrabecular matrix and trabecular bone is reproducible in a human 3D in vitro model. This study illustrates the importance of updating the view on long‐term consequences of biomaterial usage and reveals toxicokinetics within highly sensitive organs., Spatially micron‐ and nanoresolved synchrotron X‐ray fluorescence analyses of peri‐implant cancellous bone reveal specific distribution and accumulation patterns of metals released from alloys frequently used in knee and hip arthroplasty. These new insights of the local toxicokinetics of metallic debris prove that cobalt, chromium, and titanium exposure also occurs behind the insulating implant membrane, in the bone and bone marrow.

This booklet has been produced by the partners of the EPRISE project. It provides an overview of the opportunities for photonics in the Medical Technology, Pharmaceutical, Agriculture, and Food sectors as well as information useful for SMEs to overcome market-entry barriers. It gathers the most relevant outcomes of the European Photonics Roadshow, including best practices, lessons learnt, takeaways and tips from experts. Information consists of: • general articles presenting target market trends and possible applications of photonics, and highlighting how the latter can contribute to solve societal challenges; • technical articles dealing with both market-specific topics such as clinical trials and pharmaceutical clinical trials and cross-sectoral themes such as access to finance, Intellectual Property (IP), start-up support, internationalisation. Finally, one case study per market has been selected as an example of challenges commonly faced by companies (scale-up manufacturing and regulatory strategy, access to large companies and IP strategy, recognition from end users, diversification). The booklet mainly targets photonics SMEs entering the four target markets to help them enhance their business skills, but also integrators and end users to increase their awareness of the potential of photonics-based solutions in their sector. Printed booklets will be distributed amongst the members of the EPRISE partners (photonics supply chain) and their regional and national funding bodies to stimulate investment in photonics ventures. The booklet will be also available on the project website in the form of e-book. This will enable larger dissemination towards local sectoral clusters and photonics clusters not part of the consortium, and companies active in other technological areas (e.g. robotics) to foster collaborative projects in the target markets.

Additional Methods. Figure S1. Nano-X-ray fluorescence (XRF) maps of four skin and three lymph node samples analyzed at ID16B. Figure S2. Nano-X-ray fluorescence (XRF) maps of selected inks analyzed at ID16B. Figure S3. Calculation of Ni and Cr contamination in pig skin and inks. Figure S4. T-cell infiltration in tattoo allergy sample. Table S1. Titanium XANES spectra of eight human skin and six lymph node samples as well as a skin allergy biopsy were fitted to pure anatase and rutile spectra of known standards. Table S2. MALDI-MS analysis of organic pigments in skin and lymph node samples. No pigments were found in the control samples. Table S3. Cr K-edge micro-XANES spectra of human skin and lymph node samples were fitted to spectra of known Cr standards. Table S4. Ni K-edge nano-XANES spectra of human skin and lymph node samples were fitted to known Ni standards. Table S5. ICP-MS analysis of elements in skin and lymph node samples. Increased values compared to skin or lymph node (LN) control samples are marked in bold. Table S6. Table-top X-ray fluorescence (XRF) analysis of microtome blades used for sample preparation and commercial tattoo needles. Tattoo needles analyzed derived from six different brands. Data are displayed as mean and standard deviation of n = 2 measurements. (DOCX 3000 kb)

International audience; For biomedical research, successful imaging of calcified microstructures often relies on absorption differences between features, or on employing dies with selective affinity to areas of interest. When texture is concerned, e.g. for crystal orientation studies, polarization induced contrast is of particular interest. This requires sufficient interaction of the incoming radiation with the volume of interest in the sample to produce orientation-based contrast. Here we demonstrate polarization induced contrast at the calcium K-edge using submicron sized monochromatic synchrotron X-ray beams. We exploit the orientation dependent subtle absorption differences of hydroxyl-apatite crystals in teeth, with respect to the polarization field of the beam. Interaction occurs with the fully mineralized samples, such that differences in density do not contribute to the contrast. Our results show how polarization induced contrast X-ray fluorescence mapping at specific energies of the calcium K-edge reveals the micrometer and submicrometer crystal arrangements in human tooth tissues. This facilitates combining both high spatial resolution and large fields of view, achieved in relatively short acquisition times in reflection geometry. In enamel we observe the varying crystal orientations of the micron sized prisms exposed on our prepared surface. We easily reproduce crystal orientation maps, typically observed in polished thin sections. We even reveal maps of submicrometer mineralization fronts in spherulites in intertubular dentine. This Ca K-edge polarization sensitive method (XRF-PIC) does not require thin samples for transmission nor extensive sample preparation. It can be used on both fresh, moist samples as well as fossilized samples where the information of interests lies in the crystal orientations and where the crystalline domains extend several micrometers beneath the exposed surface.

Diese Arbeit befasst sich mit Joe Bergers Märchen, welche in den Bänden „Märchen für Konsumkinder“ (1977) und „Märchen für die Satten und Irren“ (1990) erschienen sind. Zudem beinhaltet der Sammelband „Von Bestsellern und riesengroßen Brüsten“ (2012) auch bis dahin unveröffentlichte Märchen, die ebenso Gegenstand der Auseinandersetzung sind. In diesen Texten thematisiert Berger auf komödiantische Weise verschiedenste gesellschaftspolitische Entwicklungen. Im Fokus der Arbeit stehen zum einen Bergers intertextuelle Verfahrensweisen. Er bedient sich dabei auf verschiedene Arten am Gerüst der Gattung Märchen und adaptiert es für seine Zwecke. Mit besagten Zwecken stehen zum anderen Bergers subversive Absichten und vor allem seine entsprechenden Strategien im Zentrum des Interesses. Das Ergebnis der Analysen soll zeigen, inwiefern innerhalb von Bergers Märchen die intertextuellen Bezüge Voraussetzungen für seine subversiven Absichten darstellen.

International audience; In bone remodeling, maturation of the newly formed osteonal tissue is associated with a rapid primary increase followed by a slower secondary increase of mineralization. This requires supply and precipitation of mineral into the bone matrix. Mineral delivery can occur only from the extracellular fluid via interfaces such as the Haversian system and the osteocyte pore network. We hypothesized that in mineralization, mineral exchange is achieved by the diffusion of mineral from the lacunar-canalicular network (LCN) to the bone matrix, resulting in a gradual change in tissue mineralization with respect to the distance from the pore-matrix interface. We expected to observe alterations in the mass density distribution with tissue age. We further hypothesized that mineral exchange occurs not only at the lacunar but also at the canalicular boundaries. The aim of this study was, therefore, to investigate the spatial distribution of mass density in the perilacunar and pericanalicular bone matrix and to explore how these densities are influenced by tissue aging. This is achieved by analyzing human jawbone specimens originating from four healthy donors and four treated with high-dosage bisphosphonate using synchrotron radiation phase-contrast nano-CT with a 50-nm voxel size. Our results provide the first experimental evidence that mass density in the direct vicinity of both lacunae (p

International audience; X-ray in-line phase contrast tomography has been of growing interest in biology and medicine, since it enables non-destructive, quantitative 3D imaging of samples with very high sensitivity and spatial resolution. This is mainly enabled by the relatively large propagation distances of a highly spatially coherent beam that increase phase contrast interference fringes and also the use of cutting-edge detectors. Combined with tomographic reconstruction, it gives access to the refractive index distribution in the sample [1].Here, we used magnified in-line phase nano-tomography [2] to image human bone at the cellular level. This nano-imaging technique is similar to propagation-based phase contrast, except that the beam is focused using reflective X-ray optics. The sample is placed after the focal spot, so that the beam divergence and different propagation distances induce different magnification factors.Four human femoral cortical bone samples, one healthy, one suffering from osteoporosis (OP) and two suffering from osteoarthritis (OA), were imaged at the ID22 beamline at 60 nm pixel size. This resolution gives access to 3D imaging of the lacuno-canicular network (LCN) and matrix properties such as collagen fibril orientation and sub-micrometric mineralization. The field of view at this pixel size is ~120 μm, yielding a relatively large analysed volume compared to other 3D nano-tomographic techniques ([5], [6]).Quantitative analysis will be performed to determine relevant characteristics of the LCN, as well as collagen fibril orientation [3], and mineralization of the bone matrix [4]. We will investigate changes of these cell and matrix properties in OP and OA. This methodology can be applied in other studies, providing better understanding of the link between different pathologies and bone properties on the cellular length scale.[1] P. Cloetens, W. Ludwig, J. Baruchel, D. Van Dyck, J. Van Landuyt, J. P. Guigay, and M. Schlenker, Appl. Phys. Lett.,p. 2912, 1999.[2] M. Langer, A. Pacureanu, H. Suhonen, Q. Grimal, P. Cloetens, and F. Peyrin, PLoS One, p. e35691, 2012.[3] P. Varga, A. Pacureanu, M. Langer, H. Suhonen, B. Hesse, Q. Grimal, P. Cloetens, K. Raum, and F. Peyrin, EuropeanSociety of Biomechanics, 2013.[4] B. Hesse, M. Langer, P. Varga, A. Pacureanu, P. Dong, S. Schrof, N. Männicke, H. Suhonen, C. Olivier, P. Maurer, G.J. Kazakia, K. Raum, and F. Peyrin, Plos one, p. e88481, 2014.[5] M. Dierolf, A. Menzel, P. Thibault, P. Schneider, C. M. Kewish, R. Wepf, O. Bunk, and F. Pfeiffer, Nature, pp. 436–9,2010.[6] J. C. Andrews, E. Almeida, M. C. H. van der Meulen, J. S. Alwood, C. Lee, Y. Liu, J. Chen, F. Meirer, M. Feser, J. Gelb,J. Rudati, A. Tkachuk, W. Yun, and P. Pianetta, Microsc. Microanal., pp. 327–36, 2010.

Gesunder humaner Knochen unterliegt einem permanenten Umbau, um sich den mechanischen Anforderungen anzupassen, Mikrofrakturen zu reparieren und das Mineraliengleichgewicht zu erhalten. Dieser Umbauprozess wird durch Osteoblasten- und Osteoklastenaktivität realisiert, den knochenbildenden bzw. knochenresorbierenden Zellen. Gesteuert wird dieser Prozess durch Osteozyten, dessen Netzwerk mechanosensorische Fähigkeiten zugesprochen werden. Bisphosphonate (BP), hemmen die Osteoklastenaktivität und erhöhen somit die Knochenumsatzzeit. Im ersten Teil dieser Arbeit wurden morphologische Eigenschaften der Osteozyten-Lakunen (OL) in humanem Knochen mittels Synchrotron-µCT untersucht. Dabei wurden sowohl gesunde als auch mit BP behandelte Spender verglichen. Anschließend haben wir Synchrotron-Nano-CT in Kombination mit Phasenkontrast angewandt, um unsere Untersuchungen auf die Morphologie des lakuno-kanalikulären Netzwerkes (LKN) und die Gewebeeigenschaften in der Umgebung des LKN auszuweiten. Wir nahmen an, dass der sekundäre Mineralisierungsprozess mittels eines Diffusionsprozesses durch die Grenzfläche der extrazellulären Flüssigkeit im LKN stattfindet, was zu Gradienten der Massendichte in der Umgebung des LKN führen sollte. Unsere Untersuchungen haben gezeigt, dass sowohl in der Umgebung der OL als auch der Kanäle Massendichtegradienten existieren. Daraus schließen wir, dass der Mineralienaustausch zwischen der extrazellulären Flüssigkeit und der mineralisierten Matrix an der gesamten Oberfläche des LKN stattfindet. Wir schätzten, dass die Kapazität, unter Berücksichtigung des gesamten LKN, Mineralien auszutauschen etwa eine Größenordnung höher ist, gegenüber der Annahme, dass der Austausch lediglich an den Grenzflächen der OL stattfindet. Zukünftige Studien sollten nicht nur die peri-LKN Gewebeeigenschaften während der sekundären Mineralisierung untersuchen, sondern auch Schwankungen der Mineralienkonzentration bei hohen Kalziumanforderungen des Körpers berücksichtigen. Under healthy conditions human bone undergoes permanent remodeling to adjust to mechanical demands, to repair micro-cracks and to maintain mineral homeostasis. This process of remodeling is performed by osteoblasts and osteoclasts: bone-forming and bone-resorbing cells. The activity of osteoclasts and osteoblasts is triggered by osteocytes, the most frequently occurring type of bone cell, via mechanosensation processes. Bisphosphonates (BP) prescribed during treatment for osteoporosis or bone metastasis inhibit osteoclast activity and thus decrease the bone turnover. In this work, the distribution and morphology of osteocyte lacunae of human cortical jaw bone was investigated in 3D, and a comparison between healthy and BP-treated donors was performed using synchrotron radiation (SR) µCT. In a second approach, we used SR nano-CT with phase contrast to investigate the morphology of the canalicular network and the bone tissue properties in the vicinity of the lacuna-canalicular network of human jaw bone, originating from both healthy subjects and patients treated with BPs. We hypothesized that secondary mineralization takes place via a diffusion process through the fluid-matrix interface at both the lacunar and the canalicular surfaces. This should result in mass density gradients with respect to the distance to the pore boundary. Such mass density gradients were indeed observed at both lacunar and canalicular interfaces. We concluded that mineral exchange between extracellular fluid and mineralized matrix occurs at all bone surfaces, including the canaliculi. Our data suggested that the capacity of the pore network to exchange mineral with the bone matrix would increase by one order of magnitude if the canalicular surface is taken into account. However, more studies should be performed, targeting not only the changes of tissue properties during secondary mineralization, but also during fluctuations of mineral concentration in periods of high mineral demand.

International audience; The architectural properties of the osteocyte cell network provide a valuable basis for understanding the mechanisms of bone remodelling, mineral homeostasis, ageing and pathologies. Recent advances in synchrotron microtomography enable unprecedented three-dimensional imaging of both the bone lacunar network and the extracellular matrix. Here, we investigate the three-dimensional morphological properties of osteocyte lacunae in human healthy and bisphosphonate-related osteonecrotic jaw bone based on synchrotron X-ray computed tomography images, with a spatial isotropic voxel size of 300 nm. Bisphosphonate-related osteonecrosis of the jaw is a relatively new disease with increasing incidence, which remains poorly understood. A step forward in elucidating this malady is to assess whether, and how, the morphology of the osteocyte lacunar network is modified in the affected jaw tissue. We evaluate thousands of cell lacunae from five specimens of which three originate from patients diagnosed with bisphosphonate-associated osteonecrosis. In this exploratory study, we report three-dimensional quantitative results on lacunar volumes (296-502 μm3), shape (approximated by an ellipsoidal shape with principal axes a > b > c, such that a = 2.2b and a = 4c) and spatial distribution (i.e., 50% of the mineralized matrix volume is located within 12 μm to the closest lacunar boundary) at submicron resolution on such specimens. We observe that the average lacunar volumes of the bisphosphonate-related osteonecrotic jaw specimens were within the range of volumes found in the two specimens originating from healthy donors and conclude that lacunar volumes are not the key element in the course of bisphosphonate-related osteonecrotic jaw. In three out of five specimens we observe lacunar volume sizes in segmented osteons to be significantly different compared to lacunar volumes in the adjacent tissue regions. Furthermore, we quantify the number of lacunae containing small dense objects (on average 9%). In contrast to lacunar morphology we report the lacunar density (16 000-50 000 per mm3) to be different in jaw bone tissue compared to what has been reported in femoral sites.

Fragestellung: Während der initialen Phase der Knochenregeneration lassen nicht-mineralisierte Gewebsformationen Rückschlüsse auf das wahrscheinliche Heilungsergebnis zu. Derzeit etablierte Methoden zur Erfassung dieser sogenannten Soft-Kallus-Formationen sind limitiert auf röntgenbasierte[for full text, please go to the a.m. URL], Deutscher Kongress für Orthopädie und Unfallchirurgie (DKOU 2013)

n/a

n/a

n/a

International audience

This booklet has been produced by the partners of the EPRISE project. It provides an overview of the opportunities for photonics in the Medical Technology, Pharmaceutical, Agriculture, and Food sectors as well as information useful for SMEs to overcome market-entry barriers. It gathers the most relevant outcomes of the European Photonics Roadshow, including best practices, lessons learnt, takeaways and tips from experts. Information consists of: • general articles presenting target market trends and possible applications of photonics, and highlighting how the latter can contribute to solve societal challenges; • technical articles dealing with both market-specific topics such as clinical trials and pharmaceutical clinical trials and cross-sectoral themes such as access to finance, Intellectual Property (IP), start-up support, internationalisation. Finally, one case study per market has been selected as an example of challenges commonly faced by companies (scale-up manufacturing and regulatory strategy, access to large companies and IP strategy, recognition from end users, diversification). The booklet mainly targets photonics SMEs entering the four target markets to help them enhance their business skills, but also integrators and end users to increase their awareness of the potential of photonics-based solutions in their sector. Printed booklets will be distributed amongst the members of the EPRISE partners (photonics supply chain) and their regional and national funding bodies to stimulate investment in photonics ventures. The booklet will be also available on the project website in the form of e-book. This will enable larger dissemination towards local sectoral clusters and photonics clusters not part of the consortium, and companies active in other technological areas (e.g. robotics) to foster collaborative projects in the target markets.

This booklet has been produced by the partners of the EPRISE project. It provides an overview of the opportunities for photonics in the Medical Technology, Pharmaceutical, Agriculture, and Food sectors as well as information useful for SMEs to overcome market-entry barriers. It gathers the most relevant outcomes of the European Photonics Roadshow, including best practices, lessons learnt, takeaways and tips from experts. Information consists of: • general articles presenting target market trends and possible applications of photonics, and highlighting how the latter can contribute to solve societal challenges; • technical articles dealing with both market-specific topics such as clinical trials and pharmaceutical clinical trials and cross-sectoral themes such as access to finance, Intellectual Property (IP), start-up support, internationalisation. Finally, one case study per market has been selected as an example of challenges commonly faced by companies (scale-up manufacturing and regulatory strategy, access to large companies and IP strategy, recognition from end users, diversification). The booklet mainly targets photonics SMEs entering the four target markets to help them enhance their business skills, but also integrators and end users to increase their awareness of the potential of photonics-based solutions in their sector. Printed booklets will be distributed amongst the members of the EPRISE partners (photonics supply chain) and their regional and national funding bodies to stimulate investment in photonics ventures. The booklet will be also available on the project website in the form of e-book. This will enable larger dissemination towards local sectoral clusters and photonics clusters not part of the consortium, and companies active in other technological areas (e.g. robotics) to foster collaborative projects in the target markets. &nbsp