A simple and versatile micro contact printing method for generating carbon nanotubes patterns on various substrates

We present an optimized process for generating at low cost, patterns of carbon nanotubes (CNTs) on a large variety of substrates through a simple micro contact printing method. This method meets the requirements for the integration of CNTs into microdevices, for applications in microelectronics (interconnects), flexible electronics (printed conductive electrodes) and biodevices (biosensors and biosystems for regenerative medicine). We have optimized a new method for inking PolyDiMethylSiloxane (PDMS) stamps with CNTs that turned out to improve significantly the quality of the printed features over large surfaces. This inking step is performed by adapting a spray-coating process leading to a dense and homogeneous coating of the stamp with a thin layer of CNTs. The printing step is performed using a solvent mediation, allowing us to pattern this thin layer of CNTs onto various substrates by contact through a thin film of liquid. We demonstrate that this soft and rapid methodology can lead to the realization of CNTs patterns with versatile geometries onto various substrates at the micron scale. Examples of applications for CNTs interconnects and flexible electronics are rapidly shown

Multi-scale engineering for neuronal cell growth and differentiation

In this paper we investigate the role of micropatterning and molecular coating for cell culture and differentiation of neuronal cells (Neuro2a cell line) on a polydimethylsiloxane substrate. We investigate arrays of micrometric grooves (line and space) capable to guide neurite along their axis. We demonstrate that pattern dimensions play a major role due to the deformation of the cell occasioned by grooves narrower than typical cell dimension. A technological compromise for optimizing cell density, differentiation rate and neurite alignment has been obtained for 20 lm wide grooves which is a dimension comparable with the average cell dimension. This topographical engineered pattern combined with double-wall carbon nanotubes coating enabled us to obtain adherent cell densities in the order of 104 cells/cm2 and a differentiation rate close to 100%

Inhibition of Cancer Cell Migration by Multiwalled Carbon Nanotubes

Inhibiting cancer cell migration and infiltration to other tissues makes the difference between life and death. Multiwalled carbon nanotubes (MWCNTs) display intrinsic biomimetic properties with microtubules, severely interfering with the function of these protein filaments during cell proliferation, triggering cell death. Here it is shown MWCNTs disrupt the centrosomal microtubule cytoskeletal organization triggering potent antimigratory effects in different cancer cells

Elucidation of the Role of Carbon Nanotube Patterns on the Development of Cultured Neuronal Cells.

Carbon nanotubes (CNTs) promise various novel neural biomedical applications for interfacing neurons with electronic devices or to design appropriate biomaterials for tissue regeneration. In this study, we use a new methodology to pattern SiO2 cell culture surfaces with double-walled carbon nanotubes (DWNTs). In contrast to homogeneous surfaces, patterned surfaces allow us to investigate new phenomena about the interactions between neural cells and CNTs. Our results demonstrate that thin layers of DWNTs can serve as effective substrates for neural cell culture. Growing neurons sense the physical and chemical properties of the local substrate in a contact-dependent manner and retrieve essential guidance cues. Cells exhibit comparable adhesion and differentiation scores on homogeneous CNT layers and on a homogeneous control SiO2 surface. Conversely, on patterned surfaces, it is found that cells preferentially grow on CNT patterns and that neurites are guided by micrometric CNT patterns. To further elucidate this observation, we investigate the interactions between CNTs and proteins that are contained in the cell culture medium by using quartz crystal microbalance measurements. Finally, we show that protein adsorption is enhanced on CNT features and that this effect is thickness dependent. CNTs seem to act as a sponge for culture medium elements, possibly explaining the selectivity in cell growth localization and differentiation

Controlling the Outgrowth and Functions of Neural Stem Cells: The Effect of Surface Topography

Neural stem cells (NSCs) are self-renewing cells that generate the major cell types of the central nervous system, namely neurons, astrocytes and oligodendrocytes, during embryonic development and in the adult brain. NSCs reside in a complex niche where they are exposed to a plethora of signals, including both soluble and physical signals such as compressive and shear stresses, but also discontinuities and differences in morphology of the extracellular environment, termed as topographical features. Different approaches that incorporate artificial micro- and nano-scale surface topographical features have been developed aiming to recapitulate the in vivo NSC niche discontinuities and features, particularly for in vitro studies. The present review article aims at reviewing the existing body of literature on the use of artificial micro- and nano-topographical features to control NSCs orientation and differentiation into neuronal and/or neuroglial lineage. The different approaches on the study of the underlying mechanism of the topography-guided NSC responses are additionally revised and discussed

Micro/Nano ingénierie pour le contrôle de la croissance de cellules neuronales et l'élaboration d'une bioprothèse cérébrale à base de cellules souches organisées

Brain pathologies are often characterized by cell population losses. One promising therapeutic approach consists in using bioactive biomaterials, combining a cellular graft and biopolymers, acting as scaffold to build new tissues in vitro, which will then be implanted in vivo. In this thesis, we develop a brain bioprosthesis that combines the regenerative role of adult human neural stem cells with the control of cells behavior by microtopography and carbon nanotubes. The first part is dedicated to in vitro experiments that focus on the interactions between various neuronal cell types and topographical cues. We show that topographical patterns generated on a non-cytotoxic polymer (PDMS) strongly influence the development of neuronal networks. We also demonstrate that carbon nanotube thin layers constitute a favorable substrate to culture various types of neuronal cells. We then propose an explanation to further understand the role of carbon nanotubes on neuronal cell growth. The second part is dedicated to the elaboration of a brain bioprosthesis for the rat. The objective of this bioprosthesis is to reconstruct a lost brain tissue located in the primary motor zone of the cortex, which is responsible for the motricity. Brain bioprosthesis development considers all requirements related to stem cell culture and neurosurgery. It is made of microstructured PDMS and incorporates adult stem cells predifferentiated in vitro into neurons and astrocytes. Our first results obtained in vivo show a partial functional recovery of rats after the implantation of the bioprosthesis in the region of an induced brain lesion.Les pathologies du système nerveux central sont souvent caractérisées par des pertes de populations cellulaires. Une voie thérapeutique prometteuse en développement consiste à utiliser des biomatériaux bioactifs, associant une greffe de cellules et des biopolymères servant d'échafaudage pour la confection des nouveaux tissus in vitro, implantés in vivo. Dans cette thèse, nous développons une bioprothèse cérébrale qui combine le potentiel régénératif des cellules souches adultes humaines avec un pilotage du comportement de ces cellules par la microtopographie et les nanotubes de carbone. Dans une première partie, dédiée aux études in vitro des interactions entre différents types de cellules neuronales et des indices topographiques, nous montrons que la variation de la géométrie de microsillons créés sur la surface d'un polymère non cytotoxique, le PDMS, permet de déterminer l'architecture des réseaux neuronaux développés. Nous démontrons aussi que les nanotubes de carbone déposés sur des surfaces sous forme de couches constituent un substrat favorable pour le développement des cellules neuronales, et proposons une nouvelle explication de leur rôle dans la culture cellulaire. Dans une deuxième partie, nous utilisons ces résultats pour élaborer une bioprothèse cérébrale pour le rat visant à reconstituer un tissu lésé, dans le cortex moteur responsable de la motricité. L'architecture de la bioprothèse développée intègre les impératifs liés à la culture de cellules souches et liés à la neurochirurgie. Elle est faite en PDMS qui est microstructuré en surface et comporte des cellules souches neurales adultes prédifférenciées en neurones. Nos premiers essais d'implantation chez le rat montrent une récupération fonctionnelle partielle de la motricité des animau

Particle suitable for the manufacture of an implantable soft tissue engineering material

The particle (1) is suitable for the manufacture of an implantable soft tissue engineering material and comprises: a three-dimensionally warped and branched sheet (2) where (i) the three-dimensionally warped and branched sheet (2) is made from a biocompatible material having a Young's modulus of 1kPa to 1GPa; (ii) the three-dimensionally warped and branched sheet (2) has an irregular shape which is encompassed in a virtual three-dimensional envelope (3) having a volume VE; (iii) the three-dimensionally warped and branched sheet (2) has a mean sheet thickness T; iv) the three-dimensionally warped and branched sheet (2) has a volume VS; (v) the particle (1) has a Young's modulus of 100Pa to 15kPa; and (vi) the particle (1) further comprises a number of protrusions (4) where the three-dimensionally warped and branched sheet (2) reaches the envelope (3); (vii) the particle (1) has a number of interconnected channel-type conduits (5) defined by the branching of the sheet (2) and/or by voids in the sheet (2); and (viii) where the conduits (5) have (a) a mean diameter DC; and (b) an anisotropicity index of 1.01 to 5.00

Cryogel 3d scaffolds and methods for producing thereof

A method of producing a cryogel-based multicompartment 3D scaffold is herein disclosed. The method comprises the steps of: a) providing a first frozen polymeric layer on a refrigerated support kept at subzero temperature; b) providing subsequent polymeric layers to obtain a stack of polymeric layers by possibly modulating the subzero temperature of the refrigerated support; c) optionally incubating the final polymeric structure at subzero temperature; and d) placing the produced cryogel at a temperature above 0° C., the method being characterized in that each subsequent layer i) is deposited on the previous one after freezing of this latter; ii) is deposited on the previous one before the complete polymerization of this latter; and iii) is deposited with a temperature higher than the freezing temperature of the previously deposited layer. Cryogel scaffolds obtained from the method of the invention are also disclosed

Micro/nano-ingénierie pour le contrôle de la croissance de cellules neuronales et ingénierie tissulaire appliquée au système nerveux central

Les pathologies du système nerveux central sont souvent caractérisées par des pertes de populations cellulaires. Une voie thérapeutique prometteuse en développement consiste à utiliser des biomatériaux bioactifs, associant une greffe de cellules et des biopolymères servant d’échafaudage pour la confection des nouveaux tissus in vitro, ensuite implantés in vivo. Dans cet article, un état de l’art de ce domaine, à la croisée entre la microtechnologie et la neuroscience, est détaillé, puis nos travaux et résultats portant sur l’étude des interactions des cellules souches neurales adultes humaines et des polymères microstructurés sont résumés et discutés. Dans un deuxième temps, certaines stratégies de réparation du système nerveux central, basées sur l’ingénierie tissulaire cérébrale, sont présentées et nous exposons les principaux résultats de nos travaux portant sur l’élaboration et la caractérisation in vivo d’une bioprothèse cérébrale

Ophthalmic contact lens with a compressible affinity matrix

The invention relates to a contact lens for use in the treatment of ocular inflammatory pathologies. The contact lens comprises a soft porous material coupled, in certain embodiments, with detoxifying agents. Said material and/or agents contact and neutralize inflammatory mediators present in the tear fluid of ocular pathologies patients. The nature and architecture of the soft porous material allows a greater contact area between the material itself and/or detoxifying agents with inflammatory mediators, in view of the reversible compression of the soft material that allows greater lachrymal fluid turnover and fluid exchange within the contact lens upon e.g. blinking