72 research outputs found

    Local deformation in a hydrogel induced by an external magnetic field

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    The aim of this study is to prove the feasibility of a system able to apply local mechanical loading on cells seeded in a hydrogel for tissue engineering applications. This experimental study is based on a previously developed artificial cartilage model with different concentrations of poly(vinyl alcohol) (PVA) that simulates the cartilage extracellular matrix (ECM). Poly(l-lactic acid) (PLLA) microspheres with dispersed magnetic nanoparticles (MNPs) were produced with an emulsion method. These microspheres were embedded in aqueous PVA solutions with varying concentration to resemble increased viscosity of growing tissue during regeneration. The ability to induce a local deformation in the ECM was assessed by applying a steady or an oscillatory magnetic field gradient to different PVA solutions containing the magnetic microparticles, similarly as in ferrogels. PLLA microparticle motion was recorded, and the images were analyzed. Besides, PVA gels and PLLA microparticles were introduced into the pores of a polycaprolactone scaffold, and the microparticle distribution and the mechanical properties of the construct were evaluated. The results of this experimental model show that the dispersion of PLLA microparticles containing MNPs, together with cells in a supporting gel, will allow applying local mechanical stimuli to cells during tissue regeneration. This local stimulation can have a positive effect on the differentiation of seeded cells and improve tissue regeneration.The authors gratefully acknowledge the financial support from the Spanish Ministry of Economy and Competitiveness through the MAT2013-46467-C4-1-R project, including the Feder funds. CIBER-BBN is an initiative funded by the VI National R&D&I Plan 2008-2011, Iniciativa Ingenio 2010, Consolider Program. CIBER Actions are financed by the Instituto de Salud Carlos III with assistance from the European Regional Development Fund. The authors thank "Servicio de Microscopia Electronica" of Universitat Politecnica de Valencia for their invaluable help. The translation of this paper was funded by the Universitat Politecnica de Valencia, Spain.Vikingsson, L.; Vinals Guitart, Á.; Valera Martínez, A.; Riera Guasp, J.; Vidaurre Garayo, AJ.; Gallego Ferrer, G.; Gómez Ribelles, JL. (2016). Local deformation in a hydrogel induced by an external magnetic field. Journal of Materials Science. 51(22):9979-9990. https://doi.org/10.1007/s10853-016-0226-8S997999905122Eyre D (2002) Collagen of articular cartilage. Arthritis Res 4:30–35Roughley PJ, Lee ER (1994) Cartilage proteoglycans: structure and potential functions. Microsc Res Tech 28:385–397Gillard GC, Reilly HC, Bell-Booth PG, Flint MH (1979) The influence of mechanical forces on the glycosaminoglycan content of the rabbit flexor digitorum profundus tendon. Connect Tissue Res 7:37–46Quinn TM, Grodzinsky AJ, Buschmann MD, Kim YJ, Hunziker EB (1998) Mechanical compression alters proteoglycan deposition and matrix deformation around individual cells in cartilage explants. J Cell Sci 111:573–583Banes AJ, Tsuzaki M, Yamamoto J, Fischer T, Brigman B, Brown T, Miller L (1995) Mechanoreception at the cellular level: the detection, interpretation, and diversity of responses to mechanical signals. Biochem Cell Biol 73:349–365Appelman T, Mizrahi J, Elisseeff J, Seliktar D (2011) The influence of biological motifs and dynamic mechanical stimulation in hydrogel scaffold systems on the phenotype of chondrocytes. Biomaterials 32:1508–1516Mow VC, Ratcliffe A, Poole AR (1992) Cartilage and diarthrodial joints as paradigms for hierarchical materials and structures. Biomaterials 13:67–97Mow VC, Huiskes R (2005) Basic orthopaedic biomechanics and mechano-biology. Lippincott Williams and Wilkins, PhiladelphiaBrady MA, Waldman SD, Ethier CR (2015) The application of multiple biophysical cues to engineer functional neocartilage for treatment of osteoarthritis. Part I: cellular response. Tissue Eng Part B Rev 21:1–19Valhmu WB, Stazzone EJ, Bachrach NM, Saed-Nejad F, Fischer SG, Mow VC, Ratcliffe A (1998) Load-controlled compression of articular cartilage induces a transient stimulation of aggrecan gene expression. Arch Biochem Biophys 353:29–36Ingber DE (1997) Tensegrity: the architectural basis of cellular mechanotransduction. Ann Rev Physiol 59:575–599Khan S, Sheetz MP (1997) Force effects on biochemical kinetics. Ann Rev Biochem 66:785–805Hutmacher DW (2000) Scaffolds in tissue engineering bone and cartilage. Biomaterials 21:2529–2543Crick FHC, Hughes AFW (1950) The physical properties of cytoplasm: a study by means of the magnetic particle method. Exp Cell Res 1:37–80Valberg PA, Albertini DF (1985) Cytoplasmic motions, rheology, and structure probed by a novel magnetic particle method. J Cell Biol 101:130–140Valberg PA, Feldman HA (1987) Magnetic particle motions within living cells. Measurement of cytoplasmic viscosity and motile activity. Biophys J 52:551–561Wang N, Ingber DE (1995) Probing transmembrane mechanical coupling and cytomechanics using magnetic twisting cytometry. Biochem Cell Biol 73:327–335Pommerenke H, Schreiber E, Durr F, Nebe B, Hahnel C, Moller W, Rychly J (1996) Stimulation of integrin receptors using a magnetic drag force device induces an intracellular free calcium response. Eur J Cell Biol 70:157–164Bausch AR, Hellerer U, Essler M, Aepfelbacher M, Sackmann E (2001) Rapid stiffening of integrin receptor-actin linkages in endothelial cells stimulated with thrombin: a magnetic bead microrheology study. Biophys J 80:2649–2657Li L, Yang G, Li J, Ding S, Zhou S (2014) Cell behaviors on magnetic electrospun poly-d, l-lactide nano fibers. Mater Sci Eng, C 34:252–261Fuhrer R, Hofmann S, Hild N, Vetsch JR, Herrmann IK, Grass RN, Stark WJ (2013) Pressureless mechanical induction of stem cell differentiation is dose and frequency dependent. PLoS One 8:e81362Cezar CA, Roche ET, Vandenburgh HH, Duda GN, Walsh CJ, Mooney DJ (2016) Biologic-free mechanically induced muscle regeneration. Proc Natl Acad Sci USA 113:1534–1539Vikingsson L, Gallego Ferrer G, Gómez-Tejedor JA, Gómez Ribelles JL (2014) An in vitro experimental model to predict the mechanical behaviour of macroporous scaffolds implanted in articular cartilage. J Mech Behav Biomed Mater 32:125–131Vikingsson L, Gomez-Tejedor JA, Gallego Ferrer G, Gomez Ribelles JL (2015) An experimental fatigue study of a porous scaffold for the regeneration of articular cartilage. J Biomech 48:1310–1317Vikingsson L, Claessens B, Gómez-Tejedor JA, Gallego Ferrer G, Gómez Ribelles JL (2015) Relationship between micro-porosity, water permeability and mechanical behavior in scaffolds for cartilage engineering. J Mech Behav Biomed Mater 48:60–69Li F, Su YL, Shi DF, Wang CT (2010) Comparison of human articular cartilage and polyvinyl alcohol hydrogel as artificial cartilage in microstructure analysis and unconfined compression. Adv Mater Res Trans Tech Publ 87:188–193Grant C, Twigg P, Egan A, Moody A, Eagland D, Crowther N, Britland S (2006) Poly(vinyl alcohol) hydrogel as a biocompatible viscoelastic mimetic for articular cartilage. Biotechnol Prog 22:1400–1406Weeber R, Kantorovich S, Holm C (2015) Ferrogels cross-linked by magnetic nanoparticles—Deformation mechanisms in two and three dimensions studied by means of computer simulations. J Magn Magn Mater 383:262–266Lebourg M, Suay Antón J, Gómez Ribelles JL (2008) Porous membranes of PLLA–PCL blend for tissue engineering applications. Eur Polym J 44:2207–2218Santamaría VA, Deplaine H, Mariggió D, Villanueva-Molines AR, García-Aznar JM, Gómez Ribelles JL, Doblaré M, Gallego Ferrer G, Ochoa I (2012) Influence of the macro and micro-porous structure on the mechanical behavior of poly (l-lactic acid) scaffolds. J Non Cryst Solids 358:3141–3149Panadero JA, Vikingsson L, Gomez Ribelles JL, Lanceros-Mendez S, Sencadas V (2015) In vitro mechanical fatigue behaviour of poly-ε-caprolactone macroporous scaffolds for cartilage tissue engineering. Influence of pore filling by a poly(vinyl alcohol) gel. J Biomed Mater Res Part B Appl Biomater 103:1037–1043Hassan CM, Peppas NA (2000) Structure and applications of poly(vinyl alcohol) hydrogels produced by conventional crosslinking or by freezing/thawing methods. 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    Robustness of potential biological removal to monitoring, environmental, and management uncertainties

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    Support for this project was provided by the Lenfest Ocean Program.The potential biological removal (PBR) formula used to determine a reference point for human-caused mortality of marine mammals in the United States has been shown to be robust to several sources of uncertainty. This study investigates the consequences of the quality of monitoring on PBR performance. It also explores stochastic and demographic uncertainty, catastrophic events, sublethal effects of interactions with fishing gear, and the situation of a marine mammal population subject to bycatch in two fisheries, only one of which is managed. Results are presented for two pinniped and two cetacean life histories. Bias in abundance estimates and whether there is a linear relationship between abundance estimates and true abundance most influence conservation performance. Catastrophic events and trends in natural mortality have larger effects than environmental stochasticity. Managing only one of two fisheries with significant bycatch leads, as expected, to a lower probability of achieving conservation management goals, and better outcomes would be achieved if bycatch in all fisheries were managed. The results are qualitatively the same for the four life histories, but estimates of the probability of population recovery differ.Publisher PDFPeer reviewe

    Time evolution of in vivo articular cartilage repair induced by bone marrow stimulation and scaffold implantation in rabbits

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    Purpose: Tissue engineering techniques were used to study cartilage repair over a 12-month period in a rabbit model. Methods: A full-depth chondral defect along with subchondral bone injury were originated in the knee joint, where a biostable porous scaffold was implanted, synthesized of poly(ethyl acrylate-co-hydroxyethyl acrylate) copolymer. Morphological evolution of cartilage repair was studied 1 and 2 weeks, and 1, 3, and 12 months after implantation by histological techniques. The 3-month group was chosen to compare cartilage repair to an additional group where scaffolds were preseeded with allogeneic chondrocytes before implantation, and also to controls, who underwent the same surgery procedure, with no scaffold implantation. Results: Neotissue growth was first observed in the deepest scaffold pores 1 week after implantation, which spread thereafter; 3 months later scaffold pores were filled mostly with cartilaginous tissue in superficial and middle zones, and with bone tissue adjacent to subchondral bone. Simultaneously, native chondrocytes at the edges of the defect started to proliferate 1 week after implantation; within a month those edges had grown centripetally and seemed to embed the scaffold, and after 3 months, hyaline-like cartilage was observed on the condylar surface. Preseeded scaffolds slightly improved tissue growth, although the quality of repair tissue was similar to non-preseeded scaffolds. Controls showed that fibrous cartilage was mainly filling the repair area 3 months after surgery. In the 12-month group, articular cartilage resembled the untreated surface. Conclusions: Scaffolds guided cartilaginous tissue growth in vivo, suggesting their importance in stress transmission to the cells for cartilage repair.This study was supported by the Spanish Ministry of Science and Innovation through MAT2010-21611-C03-00 project (including the FEDER financial support), by Conselleria de Educacion (Generalitat Valenciana, Spain) PROMETEO/2011/084 grant, and by CIBER-BBN en Bioingenieria, Biomateriales y Nanomedicina. The work of JLGR was partially supported by funds from the Generalitat Valenciana, ACOMP/2012/075 project. CIBER-BBN is an initiative funded by the VI National R&D&i Plan 2008-2011, Iniciativa Ingenio 2010, Consolider Program, CIBER Actions and financed by the - Instituto de Salud Carlos III with assistance from the European Regional Development Fund.Sancho-Tello Valls, M.; Forriol, F.; Gastaldi, P.; Ruiz Sauri, A.; Martín De Llano, JJ.; Novella-Maestre, E.; Antolinos Turpín, CM.... (2015). 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    Rise of oceanographic barriers in continuous populations of a cetacean: the genetic structure of harbour porpoises in Old World waters

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    <p>Abstract</p> <p>Background</p> <p>Understanding the role of seascape in shaping genetic and demographic population structure is highly challenging for marine pelagic species such as cetaceans for which there is generally little evidence of what could effectively restrict their dispersal. In the present work, we applied a combination of recent individual-based landscape genetic approaches to investigate the population genetic structure of a highly mobile extensive range cetacean, the harbour porpoise in the eastern North Atlantic, with regards to oceanographic characteristics that could constrain its dispersal.</p> <p>Results</p> <p>Analyses of 10 microsatellite loci for 752 individuals revealed that most of the sampled range in the eastern North Atlantic behaves as a 'continuous' population that widely extends over thousands of kilometres with significant isolation by distance (IBD). However, strong barriers to gene flow were detected in the south-eastern part of the range. These barriers coincided with profound changes in environmental characteristics and isolated, on a relatively small scale, porpoises from Iberian waters and on a larger scale porpoises from the Black Sea.</p> <p>Conclusion</p> <p>The presence of these barriers to gene flow that coincide with profound changes in oceanographic features, together with the spatial variation in IBD strength, provide for the first time strong evidence that physical processes have a major impact on the demographic and genetic structure of a cetacean. This genetic pattern further suggests habitat-related fragmentation of the porpoise range that is likely to intensify with predicted surface ocean warming.</p

    Rare SLC13A1 variants associate with intervertebral disc disorder highlighting role of sulfate in disc pathology.

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    To access publisher's full text version of this article, please click on the hyperlink in Additional Links field or click on the hyperlink at the top of the page marked DownloadBack pain is a common and debilitating disorder with largely unknown underlying biology. Here we report a genome-wide association study of back pain using diagnoses assigned in clinical practice; dorsalgia (119,100 cases, 909,847 controls) and intervertebral disc disorder (IDD) (58,854 cases, 922,958 controls). We identify 41 variants at 33 loci. The most significant association (ORIDD = 0.92, P = 1.6 × 10-39; ORdorsalgia = 0.92, P = 7.2 × 10-15) is with a 3'UTR variant (rs1871452-T) in CHST3, encoding a sulfotransferase enzyme expressed in intervertebral discs. The largest effects on IDD are conferred by rare (MAF = 0.07 - 0.32%) loss-of-function (LoF) variants in SLC13A1, encoding a sodium-sulfate co-transporter (LoF burden OR = 1.44, P = 3.1 × 10-11); variants that also associate with reduced serum sulfate. Genes implicated by this study are involved in cartilage and bone biology, as well as neurological and inflammatory processes.European Commission European Commission Joint Research Centre Novo Nordisk Foundation Novocure Limite

    Evidence for density-dependent changes in body condition and pregnancy rate of North Atlantic fin whales over four decades of varying environmental conditions

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    A central theme in ecology is the search for pattern in the response of a species to changing environmental conditions. Natural resource management and endangered species conservation require an understanding of density-dependent and density-independent factors that regulate populations. Marine mammal populations are expected to express density dependence in the same way as terrestrial mammals, but logistical difficulties in data acquisition for many large whale species have hindered attempts to identify population-regulation mechanisms. We explored relationships between body condition (inferred from patterns in blubber thickness) and per capita prey abundance, and between pregnancy rate and body condition in North Atlantic fin whales as environmental conditions and population size varied between 1967 and 2010. Blubber thickness in both males and females declined at low per capita prey availability, and in breeding-age females, pregnancy rate declined at low blubber thickness, demonstrating a density-dependent response of pregnancy to prey limitation mediated through body condition. To the best of our knowledge, this is the first time a quantitative relationship among per capita prey abundance, body condition, and pregnancy rate has been documented for whales. As long-lived predators, marine mammals can act as indicators of the state of marine ecosystems. Improving our understanding of the relationships that link prey, body condition, and population parameters such as pregnancy rate and survival will become increasingly useful as these systems are affected by natural and anthropogenic change. Quantifying linkages among prey, fitness and vital rates will improve our ability to predict population consequences of subtle, sublethal impacts of ocean noise and other anthropogenic stressors.Publisher PDFPeer reviewe
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