Catarina R. Pedrosa

Luxembourg Institute of Science and Technology

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J. P. Conde

Instituto de Engenharia de Sistemas e Computadores Microsistemas e Nanotecnologias

Sivashankar Krishnamoorthy

Luxembourg Institute of Science and Technology

V. Chu

Instituto de Engenharia de Sistemas e Computadores Microsistemas e Nanotecnologias

Marie‐Christine Durrieu

Institut Polytechnique de Bordeaux

Christine Labrugère

Centre National de la Recherche Scientifique

Didier Arl

Luxembourg Institute of Science and Technology

Irfan Khan

International Center for Chemical and Biological Sciences

Virgina Chu

Instituto de Engenharia de Sistemas e Computadores Microsistemas e Nanotecnologias

Narayanan Madaboosi

Indian Institute of Technology Madras

Ruben R. G. Soares

Stockholm University

Cooperative Institutions

Instituto de Engenharia de Sistemas e Computadores Microsistemas e Nanotecnologias

University of Lisbon

Centre National de la Recherche Scientifique

Université de Bordeaux

Institut Polytechnique de Bordeaux

Instituto de Engenharia de Sistemas e Computadores Investigação e Desenvolvimento

Instituto Politécnico de Lisboa

Luxembourg Institute of Science and Technology

Chimie et Biologie des Membranes et des Nanoobjects

École Polytechnique Fédérale de Lausanne

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Nanotopographies bioactives pour le contrôle de la différenciation des cellules souches mésenchymateuses pour des applications en ingénierie de tissu osseux

Catarina R. Pedrosa

Les nanotopographies de surface presentant des dimensions comparables a celles des elements de la matrice extracellulaire offrent la possibilite de reguler le comportement cellulaire. L’etude de l’impact de la nanotopographie sur la reponse cellulaire a ete toujours limitee compte tenu des precisions limitees sur les geometries produites, en particulier sur les plus grandes surfaces. Des materiaux base silicium presentant des nanopiliers avec des geometries parfaitement controlees ont ete fabriques et leur impact sur la differentiation osteogenique de cellules souches mesenchymateuses humaines (hMCSs) a ete etudie. Des materiaux avec des nanopiliers de dimensions critiques comprises entre 40 et 200 nm et des ecarts types inferieurs a 15% sur un wafer de silicium, ont ete realises en profitant de la capacite d’auto-assemblage des copolymeres a blocs. Pour mettre en evidence si des modifications de la chimie de la surface des nanopiliers pourraient favoriser la differenciation des MSCs, des peptides mimetiques ont ete greffes sur les materiaux fabriques. Un peptide connu pour sa capacite d’ameliorer l'adhesion cellulaire (peptide RGD), un peptide synthetique capable d'ameliorer l'osteogenese (peptide mimetique BMP-2) et une combinaison de ces deux peptides ont ete immobilises de maniere covalente sur les materiaux silicium presentant des nanopiliers de differentes geometries (diametre, espacement et hauteur).Les essais d'immunofluorescence et de reaction en chaine de la polymerase quantitative (RT-qPCR) revelent un impact des nanotopographies sur la differenciation osteogenique des hMSCs. De plus, il a ete constate que la differenciation des cellules dependait de l'âge du donneur. La fonctionnalisation de surface a permis une augmentation supplementaire de l'expression des marqueurs osteogeniques, en particulier lorsque le peptide RGD et le peptide mimetique BMP-2 sont co-immobilises en surface. Cette etude met clairement en evidence l’impact de nanostructures avec differentes bioactivites sur la differentiation de MSCs. Ces materiaux pourront trouver leur place dans des cultures in vitro, dans l’elaboration de nouveaux biomateriaux osseux et dans de nouveaux produits d’ingenierie tissulaire.

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Integration of Single Cell Traps, Chemical Gradient Generator and Photosensors in a Microfluidic Platform for the Study of Alpha-Synuclein Toxicity in Yeast

Procedia Engineering (2014)

João Fernandes Sandra Tenreiro Catarina R. Pedrosa Andreia Gameiro V. Chu

Alpha-synuclein (aSyn) is a key player in Parkinson's disease. Genetically engineered yeast cells producing aSyn fused with GFP (aSyn-GFP) have been used to study this protein. In this work, we present a microfluidic platform with integrated photosensors that captures single yeast cells in arrays of hydrodynamic traps and exposes them to a chemical gradient of precise composition. This platform enables the study of the effects of aSyn expression level and aggregation in genetically modified yeast cells by chemical stimulation. The photosensors allow the detection of cells in the traps by measuring the variations in light transmission or of the fluorescence produced by aSyn-GFP for real-time signal acquisition.

10.1016/j.proeng.2014.11.273

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Mesenchymal Stem Cell Differentiation Driven by Osteoinductive Bioactive Nanoscale Topographies

Applied Sciences (2021)

Catarina R. Pedrosa Christel Chanseau Christine Labrugère Sivashankar Krishnamoorthy Marie‐Christine Durrieu

Human mesenchymal stem cells (hMSCs) respond to the characteristics of their surrounding microenvironment, i.e., their extracellular matrix (ECM). The possibility of mimicking the ECM offers the opportunity to elicit specific cell behaviors. The control of surface properties of a biomaterial at the scale level of the components of the ECM has the potential to effectively modulate cell response. Ordered nanoscale silicon pillar arrays were fabricated using reverse micelles of block copolymers on full wafers, with standard deviations lower than 15%. Bioactive synthetic peptides were covalently grafted on nanoarrays to evaluate possible synergies between chemistry and topography on osteogenic differentiation of hMSCs. Functionalization with RGD (Arg-Gly-Asp) and BMP-2 (bone morphogenetic protein-2) mimetic peptides lead to an enhancement of osteogenic differentiation. Bare nanopillar arrays of reduced pitch were found to promote faster hMSC differentiation. These findings highlight the relevance of investigating possibilities of engineering in vitro systems which can be fine-tuned according to the envisaged cell response.

Nanopillar

Nanotopography

Biomaterial

Micropatterning

10.3390/app112311209

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Bioactive nanotopographies for the control of mesenchymal stem cell differentiation for applications in bone tissue engineering

HAL (Le Centre pour la Communication Scientifique Directe) (2018)

Catarina R. Pedrosa

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Bioactive nanotopographies for the control of mesenchymal stem cell differentiation for applications in bone tissue engineering

Catarina R. Pedrosa

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Microfluidic ELISA for sensing of prostate cancer biomarkers using integrated a-Si:H p-i-n photodiodes

Narayanan Madaboosi Catarina R. Pedrosa Miguel F. Reis Ruben R. G. Soares V. Chu

The accurate detection of prostate cancer (PCa) biomarkers demands improvements in both prognosis as well as diagnosis of the emerging disease. In this work, we propose the use of an immunoassay platform using polydimethylsiloxane (PDMS)-based microfluidics, with integrated optical detection based on an array of miniaturized thin-film hydrogenated amorphous silicon (a-Si:H) p-i-n photodetectors on a glass substrate. This lab-on-a-chip is compatible with fluorescence, chemiluminescence as well as colorimetric modes of detection. We present here sensing of the free isoform of prostate specific antigen (PSA) with labeled antibodies using all the three detection modes. The combination of microfluidic ELISA based on a sandwich assay and the photodiode detection can be extended, with appropriate amplification strategies, as a point-of-care tool for the multiplexing of diverse biomarkers for PCa that are often found at extremely low levels in a pathological condition and hence challenging to detect using routine bioanalytical methods.

Photodiode

Bioanalysis

Optofluidics

Lab-on-a-Chip

Polydimethylsiloxane

10.1109/icsens.2014.6985141

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Controlled Nanoscale Topographies for Osteogenic Differentiation of Mesenchymal Stem Cells

ACS Applied Materials & Interfaces (2019)

Catarina R. Pedrosa Didier Arl Patrick Grysan Irfan Khan Stéphanie Durrieu

Nanotopography with length scales of the order of extracellular matrix elements offers the possibility of regulating cell behavior. Investigation of the impact of nanotopography on cell response has been limited by the inability to precisely control geometries, especially at high spatial resolutions and across practically large areas. In this paper, we demonstrate well-controlled and periodic nanopillar arrays of silicon and investigate their impact on osteogenic differentiation of human mesenchymal stem cells (hMSCs). Silicon nanopillar arrays with critical dimensions in the range of 40–200 nm, exhibiting standard deviations below 15% across full wafers, were realized using the self-assembly of block copolymer colloids. Immunofluorescence and quantitative polymerase chain reaction measurements reveal clear dependence of osteogenic differentiation of hMSCs on the diameter and periodicity of the arrays. Further, the differentiation of hMSCs was found to be dependent on the age of the donor. While osteoblastic differentiation was found to be promoted by the pillars with larger diameters and heights independent of donor age, they were found to be different for different spacings. Pillar arrays with smaller pitch promoted differentiation from a young donor, while a larger spacing promoted those of an old donor. These findings can contribute for the development of personalized treatments of bone diseases, namely, novel implant nanostructuring depending on patient age.

10.1021/acsami.8b21393

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Microcrystalline Diamond Membrane for Electronic Monitoring of Cells in Microfluidic Perfusion Systems

Procedia Engineering (2016)

Bohuslav Rezek M. Varga Catarina R. Pedrosa Virgina Chu J. P. Conde

Self-standing microcrystalline diamond membranes were produced and embedded in three-dimensional microfluidic in-vivo-like perfusion cell culture system. Perfusion of molecules is confirmed by time-resolved fluorescent microscopy. Impedance measurements show that the diamond membranes exhibit a pronounced response to cells compared to a reference microfluidic chip without the membrane. The diamond membranes can thus be applicable as novel sensor elements in microfluidic cell reactors.

Microcrystalline

Microfluidic chip

10.1016/j.proeng.2016.11.412

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Citations (1)