1,720,973 research outputs found

    Engineered environments for biomedical applications: anisotropic nanotopographies and microfluidic devices

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    During the last two decades micro- and nano-fabrication techniques originally developed for electronic engineering have directed their attention towards life sciences. The increase of analytical power of diagnostic devices and the creation of more biomimetic scaffolds have been strongly desired by these fields, in order to have a better insight into the complexity of physiological systems, while improving the ability to model them in vitro. Technological innovations worked to fill such a gap, but the integration of these fields of science is not progressing fast enough to satisfy the expectations. In this thesis I present novel devices which exploit the unique features of the micro- and nanoscale and, at the same time, match the requirements for successful application in biomedical research. Such biochips were used for optical detection of water-dispersed nanoparticles in microchannels, for highly controlled cell-patterning in closed microreactors, and for topography-mediated regulation of cell morphology and migration. Moreover, pilot experiments on the pre-clinical translation of micropatterned scaffolds in a rat model of peripheral nerve transaction were initiated and are ongoing. Given these results, the devices presented here have the potential to achieve clinical translation in a short/medium time, contributing to the improvement of biomedical technologies

    Biocompatible noisy nanotopographies with specific directionality for controlled anisotropic cell cultures

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    All cells are exposed to extra-cellular physical stimuli determined by the details of the micro-/nano-environment within which they exist. These stimuli are present in organs and tissues where specific directional signals coexist with biotopographical noise (e.g. cellular debris, residues of apoptotic cells, protein accumulation, sclerotic plaques). Here, we present a platform for the investigation of the impact of this noise based on nanostructured plastic scaffolds with a controlled level of anisotropy. Two different types of topographical noise are introduced into fully ordered nanostructures. Starting from nanogratings, we randomly introduce nanomodifications, whose density determines the overall substrate directionality. A general quantitative definition of directionality is discussed and applied to our nanostructures. Substrate biocompatibility is assayed by culturing PC12 cells and evaluating cell viability and NGF-induced neuronal-differentiation efficiency. The suitability for high-resolution microscopy on living cells is demonstrated by visualizing focal adhesion complexes by total internal reflection fluorescence (TIRF) microscopy. Finally, we show the impact of noise in modulating focal adhesion maturation in PC12 cells upon NGF-induced neuronal differentiation. Our results indicate design rules both for biocompatible textured substrates allowing the study of cell-environment interaction in vitro and for tissue engineering applications

    Wharton's Jelly human mesenchymal stem cell contact guidance by noisy nanotopographies

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    The development of biomaterials ensuring proper cell adhesion, polarization, migration and differentiation represents a true enabler for successful tissue-engineering applications. Surface nanostructuring was suggested as a promising method for improving cell-substrate interaction. Here, we study Wharton's Jelly human Mesenchymal Stem Cells (WJ-hMSC) interacting with nanogratings (NGs) having a controlled amount of nanotopographical noise (nTN). Our data demonstrate that unperturbed NGs induce cell polarization, alignment and migration along NG lines. The introduction of nTN dramatically modifies this behavior and leads to a marked loss of cell polarization and directional migration, even at low noise levels. High-resolution focal adhesions (FAs) imaging showed that this behavior is caused by the release of the geometrical vinculum imposed by the NGs to FA shaping and maturation. We argue that highly anisotropic nanopatterned scaffolds can be successfully exploited to drive stem cell migration in regenerative medicine protocols and discuss the impact of scaffold alterations or wear

    Neuronal differentiation on anisotropic substrates and the influence of nanotopographical noise on neurite contact guidance

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    Cells are exposed to specific directional physical signals determined by the micro/nano-environment that in vivo coexist with some degree of topographical noise. Particularly in the nervous system, cell contact sensing of the extracellular environment plays a primary role in defining neurite initiation and final brain wiring. Here we study neuronal cell response to directional stimuli by exploiting nanogratings with controlled amount of random nanotopographical noise. The impact of noise on neurite guidance and focal adhesions (FAs) development is investigated in NGF-differentiating PC12 cells by confocal and TIRF microscopy. We show that the loss of neurite guidance is not linear with noise, but is a threshold effect, correlating with changes in FA maturation and spatial organization. Finally nocodazole, a drug that increases cell contractility, can improve neurite alignment by promoting aligned FA maturation. We argue that these results show new possibilities for successful implant strategies particularly in the context of nerve-regeneration devices. (C) 2013 Elsevier Ltd. All rights reserved

    Going Beyond Counting First Authors in Author Co-citation Analysis

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    The present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed

    Variations on the Author

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    “Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship

    Appropriate Similarity Measures for Author Cocitation Analysis

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    We provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
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