Bioresponsive microspheres for on‐demand delivery of anti‐inflammatory cytokines for articular cartilage repair

Despite innovations in surgical interventions, treatment of cartilage injury in osteoarthritic joints remains a challenge due to concomitant inflammation. Obstructing a single dominant inflammatory cytokine has shown remarkable clinical benefits in rheumatoid arthritis, and similar strategies are being suggested to target inflammatory pathways in osteoarthritis (OA). Here, we describe the utility of gelatin microspheres that are responsive to proteolytic enzymes typically expressed in arthritic flares, resulting in on‐demand and spatiotemporally controlled release of anti‐inflammatory cytokines for cartilage preservation and repair. These microspheres were designed with a net negative charge to sequester cationic anti‐inflammatory cytokines, and the magnitude of the negative charge potential increased with an increase in crosslinking density. Collagenase‐mediated degradation of the microspheres was dependent on the concentration of the enzyme. Release of anti‐inflammatory cytokines from the loaded microspheres directly correlated with the degradation of the gelatin matrix. Exposure of the IL‐4 and IL‐13 loaded microspheres reduced the inflammation of chondrocytes up to 80%. Hence, the delivery of these microspheres in an OA joint can attenuate the stimulation of chondrocytes and the resulting secretion of catabolic factors such as proteinases and nitric oxide. The microsphere format also allows for minimally invasive delivery and is less susceptible to mechanically induced drug release. Consequently, bioresponsive microspheres can be an effective tool for cartilage preservation and arthritis treatment.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/153665/1/jbma36852_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/153665/2/jbma36852.pd

The geometrical shape of mesenchymal stromal cells measured by quantitative shape descriptors is determined by the stiffness of the biomaterial and by cyclic tensile forces

Controlling mesenchymal stromal cell (MSC) shape is a novel method for investigating and directing MSC behaviour in vitro. it was hypothesized that specifigc MSC shapes can be generated by using stiffnessâ defined biomaterial surfaces and by applying cyclic tensile forces. Biomaterials used were thin and thick silicone sheets, fibronectin coating, and compacted collagen type I sheets. The MSC morphology was quantified by shape descriptors describing dimensions and membrane protrusions. Nanoscale stiffness was measured by atomic force microscopy and the expression of smooth muscle cell (SMC) marker genes (ACTA2, TAGLN, CNN1) by quantitative reverseâ transcription polymerase chain reaction. Cyclic stretch was applied with 2.5% or 5% amplitudes. Attachment to biomaterials with a higher stiffness yielded more elongated MSCs with fewer membrane protrusions compared with biomaterials with a lower stiffness. For cyclic stretch, compacted collagen sheets were selected, which were associated with the most elongated MSC shape across all investigated biomaterials. As expected, cyclic stretch elongated MSCs during stretch. One hour after cessation of stretch, however, MSC shape was rounder again, suggesting loss of stretchâ induced shape. Different shape descriptor values obtained by different stretch regimes correlated significantly with the expression levels of SMC marker genes. Values of approximately 0.4 for roundness and 3.4 for aspect ratio were critical for the highest expression levels of ACTA2 and CNN1. Thus, specific shape descriptor values, which can be generated using biomaterialâ associated stiffness and tensile forces, can serve as a template for the induction of specific gene expression levels in MSC. Copyright © 2017 John Wiley & Sons, Ltd.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/141253/1/term2263.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/141253/2/term2263_am.pd

Inter- and intraobserver reliability of the MTM-classification for proximal humeral fractures: A prospective study

<p>Abstract</p> <p>Background</p> <p>A precise modular topographic-morphological (MTM) classification for proximal humeral fractures may address current classification problems. The classification was developed to evaluate whether a very detailed classification exceeding the analysis of fractured parts may be a valuable tool.</p> <p>Methods</p> <p>Three observers classified plain radiographs of 22 fractures using both a simple version (fracture displacement, number of parts) and an extensive version (individual topographic fracture type and morphology) of the MTM classification. Kappa-statistics were used to determine reliability.</p> <p>Results</p> <p>An acceptable reliability was found for the simple version classifying fracture displacement and fractured main parts. Fair interobserver agreement was found for the extensive version with individual topographic fracture type and morphology.</p> <p>Conclusion</p> <p>Although the MTM-classification covers a wide spectrum of fracture types, our results indicate that the precise topographic and morphological description is not delivering reproducible results. Therefore, simplicity in fracture classification may be more useful than extensive approaches, which are not adequately reliable to address current classification problems.</p

Euro-limpacs Deliverable 189 (Work Package 7): Indicator value database for Ephemeroptera - Phase I report

The specific tasks for the ‘Indicator value database for Ephemeroptera’ are oriented to obtain two major results. The first one, by examining the Ephemeroptera literature, will provide a comprehensive picture of current knowledge concerning mayflies autoecology. The second one, by means of field data analyses, will provide new quantitative data on mayfly ecology, which will be directly related to a changing climate scenario. The literature review is a necessary tool to validate the field data being analized and to check likely modifications of taxa distribution and ecology. Once the database is implemented and completed, researchers, water managers and local surveyors will have access to a tool to assess the potential effects of climate change on freshwater ecosystems, with a special focus on the effects on the main biological traits of Ephemeroptera species

Euro-limpacs Deliverable 269 (Work Package 7): Summary of Ephemeroptera database

The present report on the European Ephemeroptera database is an outcome of the Eurolimpacs project, Work Package 7 ‘Indicators of Ecosystem Health’. It is an update of the activities presented in the deliverable 189: ‘Indicator value database for Ephemeroptera Phase I Report’ (Armanini et al., 2007) and deals with the compilation of an autoecological matrix for mayflies from literature data. In the Phase I report, the approach and methods to derive the autoecological information from the literature were described in details and here we present an overview of the full results of the activity, in terms of amount of information gained

Leitbildorientierte biologische Fliessgewaesserbewertung zur Charakterisierung des Sauerstoffhaushaltes

Available from TIB Hannover: RN 8908(2000,366) / FIZ - Fachinformationszzentrum Karlsruhe / TIB - Technische InformationsbibliothekSIGLEBundesministerium fuer Umwelt, Naturschutz und Reaktorsicherheit, Berlin (Germany)DEGerman