There are different methods used in the surgical treatment of peripheral nerve injury. In this respect, end-to-end surgical reconnection of the damaged nerve ends or autologous nerve grafts are applied as soon as possible after the injury. When autologous tissue transplant is considered, there are some medical devices available generally for relatively short nerve defects. As a solution for this problem, different tissue engineered nerve conduits have been developed. In the current study, a pHEMA hydrogel membranes were designed to mimic the tubular conduits and they were loaded with 1-6% (w/w) multiwalled carbon nanotubes (mwCNTs) to obtain electrical conductivity. The most important reason for the use of CNTs in peripheral nerve injury is their electrical conductivity. Within the context of the study, the degree of swelling, contact angles, electrical conductivity and mechanical properties of the membranes were analyzed. As the amount of mwCNTs were increased, the contact angles, indicating higher hydrophobicity and the electrical conductivity increased. The tensile test of the mwCNT-pHEMA composite membranes showed that the membranes have viscoelastic structure similar to the structure of the soft tissues. The structure of the mwCNT containing pHEMA composite membranes were analyzed with different microscopical techniques such as SEM, CSLM and microCT. MwCNTs on the hydrogels were morphologically similar to the original. SEM micrographs also showed that the mwCNTs were grouped in clumps on hydrogel surfaces. No mwCNT leaching was observed because the mwCNTs were embedded in the hydrogel, therefore, no cytotoxic effect was observed. The pHEMA hydrogels were porous which is suitable for transportation of materials, electrolytes and gas needed for cell nutrition and growth. In the in vitro studies, SHSY5Y neuroblastoma cells were seeded on the membranes to determine the sustainability and effects of the membranes on the cell growth. Electrical potential of 1 and 2 V were used to stimulate the cells. Microscopical examination with SEM and CSLM, and MTT viability assay were used. The SHSY5Y neuroblastoma cells were attached and proliferated on both the composite and the hydrogel membranes. The cells on pHEMA membranes without mwCNTs, however, were not able to survive after application of electrical potential. As a conclusion, use of composite membranes in the treatment of peripheral nerve injury as a nerve conduit is appropriate. Electrical stimulation, however, did not induce the cells to align in contrast to the expected results, indicating potential and current application regime needs to be optimized to obtain the desired results.

Sodium butyrate (NaBt) is a four-carbon short chain fatty acid, produced naturally in colon as the end product of the bacterial anaerobic metabolism on dietary fibers. It was previously shown that NaBt can induce differentiation and may inhibit proliferation. The objective of this study was to investigate the effect of NaBt-induced differentation on inflammatory pathways in HT29 colon cancer cells. For this purpose, first, cells were treated with varying concentrations of NaBt from 1-5 mM and amount required to induce differentiation was determined as 3 mM. To understand the effect of NaBt on inflammation, the NF-kappaB pathway (p50 and p65) was investigated. Immunofluorescent staining showed increased nuclear translocation of p50 subunit with no remarkable change in subcellular localization of p65 / moreover a synergistic effect was observed when cells were co-treated with NaBt and an NF-kappaB repressor, Bay 11-7085 / implying the formation of repressive p50 homodimers in the nucleus. Our preliminary chromatin immunoprecipitation results showed that p65 recruitment v to the promoters of ICAM-1 was reduced, whereas p50 recruitment was increased. However, analysis of NF-kappaB target genes showed that cells treated with 3 mM NaBt have higher expression of the cytokines IL1-&beta / and TNF-&alpha / , adhesion molecules ICAM-1 and VCAM-1 but not COX-2. These results suggest that NaBt-induced differentiation could cause the emergence of an inflammatory signal in HT29 cells as an anti-tumor mechanism, independent from the NFkappaB activity. This work will be important in understanding the role of SCFAs in the colon microenvironment and may provide alternative therapeutic options in colorectal cancer.

Some yeast strains under certain conditions secrete into the medium polypeptide toxins which are inhibitory to sensitive cells. These yeast strains are termed as killer yeasts and their toxins are designated as killer proteins or killer toxins. Killer proteins are classified into 11 typical types (K1-K11). These toxins have different killing mechanisms on sensitive cells. Some of them hydrolyze major cell wall component &amp / #946 / -1,3- glucans. As mammalian cells lack cell walls research and development of novel highly selective antifungals are mostly focused on the agents which target the components of the fungal cell wall. We have previously characterized the K5 type killer protein. This protein is an exo &amp / #946 / -1,3-glucanase which is stable at pH&rsquo / s and temperatures appropriate for its medical usage. &amp / #946 / -1,3- glucan hydrolyzing activity of the K5 type killer protein highlighted the potential use of this protein as a selective antimycotic agent. Antifungal activity of the K5 type yeast killer protein was tested against 26 human pathogenic yeast and 9 dermathophyte strains and found to be affective on all of the tested strains. Toxin MIC50, MIC100 and MFC values were found to be between 0.25-4, 0.5-8, 1-8 &micro / g/ml respectively except Candida krusei isolates. Cell killing analysis revealed that toxin activity starts within first 2 hours and complete cell death time differs due to the susceptibility of strains to the K5 type yeast killer protein. K5 type yeast killer protein would be used as a novel and selective agents with the results obtained from this study.

L’industrie aéronautique nécessite l’utilisation de métaux durs et légers, comme le Titane et l’Inconel mais différentes problématiques d’usinage en fraisage ou par usinage chimique compliquent leur mise en oeuvre. L’objectif du travail de thèse est de développer une méthode d’usinage non débouchant de ces métaux durs par jet d’eau abrasif (JEA) pour la réalisation de poches. Actuellement, ce procédé est limité à la découpe mais en contrôlant les paramètres d’usinage il permet la réalisation de poches à profondeurs constante ou variable en maitrisant les caractéristiques géométriques imposées. Ce travail présente l’étude de passages élémentaires et leur superposition afin de générer un parcours nécessaire à la réalisation d’une poche. Il introduit également diverses stratégies pour l’usinage de poches rectangulaires et propose une correction des paramètres opératoires afin d’obtenir un fond à profondeur contrôlée. / The aviation industry requires the use of hard and light metals such as Titanium and Inconel, but different machining problems in milling process or by chemical machining complicate their implementation. The aim of this thesis is to develop a controlled depth milling on these hard metals with abrasive water jet (AWJ) technology for pockets machining. Currently, this process is limited to cutting operation but by controlling the input parameters and the geometric characteristics it allows the realization of pockets with constant or variable depth. This work shows the study of elementary passages and their superposition to generate a necessary path for the realization of a pocket in AWJ. It also introduces a variety of strategies for machining rectangular pockets and provides a correction of the operating parameters to obtain a controlled depth.

Die Analyse der geometrischen Voraussetzungen der Schweißstelle bildet die Grundlage der Arbeit. Es wurde ein künstlicher Passfehler definiert, an welchem eine systematische Variation von geometrischen Parametern des Spaltes zwischen den Blechen an 22MnB5 und DC04 durchgeführt wurde. Erstmals werden die Kontaktradien durch Kennzahlen in analytischen Zusammenhang mit der Verlagerung der Wärmefreisetzung in der Umgebung der Kontakte gebracht. Am Vergütungsstahl wird vorrangig der Kontaktradius zwischen den Blechen infolge des Spaltes verringert. Erhöhte Elektrodenkraft kann dies nicht kompensieren. Messungen des dynamischen elektrischen Widerstandes charakterisieren das elektrische Verhalten der Schweißstelle und wurden mittels des KMK-Modells implizit auf den temperatur- und druckabhängigen spezifischen Übergangswiderstand übertragen. Der feueraluminierte Vergütungsstahl zeigt am Blech-Blech Kontakt einen über dreimal so hohen Übergangswiderstand wie am Elektrode-Blech Kontakt. Zeigt der 22MnB5 über 600 K grundsätzlich einen größeren Übergangswiderstand als andere Stähle, so ist bei niedrigeren Temperaturen sein Übergangswiderstand kleiner als an verschiedenen anderen Werkstoffen. Schweißversuche zeigten, dass der Linsendurchmesser an 22MnB5 infolge des Passabstandesunter den Mindestdurchmesser abnimmt, damit einher geht eine Absenkung der Schweißenergie um maximal 15 %. Durch Erhöhung des Schweißstromes sind qualitätsgerechte Schweißungen auch am Spalt möglich. Die Spritzergrenze verschiebt sich durch den Spalt zu größeren Strömen hin. Eine vertiefte Analyse der Wärmeströme zeigte, dass mindestens 30 % der Schweißwärme an den Elektrode-Blech Kontakten freigesetzt werden, mindestens 48 % entfallen auf den Stoffwiderstand des Bleches. Die Absenkung der Schweißwärme am Passfehler ist ausschließlich auf einen verminderten Stoffwiderstand zurückzuführen, welcher durch verstärktes Einsinken der Elektroden hervorgerufen wird. / The analysis of the geometric prerequisites at the weld site is the fundament of this work. An artificial form error has been defined, on which the systematic Variation of geometric parameters of the gap between sheets of 22MnB5 and DC04 have been carried out. For the first time, the contact radii have been brought into analytical relation to the relocation of heat release in the contact’s environment. On the heat-treatable steel predominantly the contact radius between the sheets is decreased as a result of the gap. Increased electrode forces cannot compensate the effect. Measurements of the electric resistance on the accurately-fitting joint characterize the electric behaviour of the weld and have been implicitly transferred to the temperature and pressure-dependent specific transition resistance by means of numerical simulation. On the sheet-sheet contact, the hot-dip aluminized heat-treatable steel showed a three times larger transition resistance than at the electrode-sheet contact. Whereas the 22MnB5 fundamentally has a bigger transition resistance than other steels above 600 K, at lower temperatures his transition resistance is superseded by that of different other steels. Welding experiments proved, that the nugget diameter in 22MnB5 is reduced below the minimum criterion by the gap. Along with this, the welding energy is reduced by a maximum of 15 %. By increasing the welding current welded joints meeting the quality criterion can be produced as well when a gap is present. The splash limit is moved to larger currents as an effect of the gap. An in-depth review of the heat flows in the welding process showed, the at least 30 % of the weld heat are released at the sheet-sheet contacts, at least 48 % are allotted to the bulk resistance of the sheets. The decrease of weld heat at the gap is exclusively attributed to a decrease of the bulk resistance of the sheets, which is generated by increased sink-in of the electrodes.

Les procédés de mise en forme des tôles métalliques sont largement utilisés dans l’industrie mécanique. La simulation numérique des opérations de mise en forme nécessite une caractérisation précise des modèles de comportement rhéologique des matériaux. Dans de nombreuses opérations de mise en forme des tôles métalliques telle que l’emboutissage, l’hydroformage, …, de grandes déformations et des vitesses de déformations dites intermédiaires peuvent être atteintes sous des états biaxiaux de déformation ou de contrainte. L’objectif de ce travail est de montrer le potentiel de l’essai de traction bi-axiale pour caractériser l’écrouissage des tôles métalliques pour de grandes déformations et dans une gamme de vitesse de déformation dite intermédiaire. A partir de simulations numériques, une forme optimale d’éprouvette en croix, permettant d’atteindre 30% de déformation plastique équivalente dans la zone centrale de l’éprouvette sous un chargement équibiaxial, a été proposée. Par la suite, des essais quasi-statiques et dynamiques de traction bi-axiale ont été réalisés sur la forme d’éprouvette proposée à partir d’une machine dédiée d’essais servo-hydraulique à quatre vérins. Dans un premier temps, le matériau choisi est un alliage d’aluminium AA5086 ne présentant pas de dépendance à la vitesse de déformation. Les déformations expérimentales sont déterminées à partir de la technique de corrélation d’images. L’écrouissage isotrope de différents modèles est identifié à partir d’une procédure inverse basée sur une modélisation éléments finis de l’essai de traction biaxiale. Trois critères de plasticité (Mises, Hill 48 et Bron et Besson) ont été successivement utilisés pour l’identification des paramètres des lois d’écrouissage. Les résultats obtenus montrent d’une part que la modélisation est très sensible au critère de plasticité choisi, et d’autre part que le critère de Bron et Besson permet d’obtenir une très bonne corrélation entre les courbes d’écrouissage identifiées à partir de l’essai bi-axial et de l’essai uni-axial. Pour les tests dynamiques bi-axiaux, les phénomènes de résonance du dispositif mécanique, générés à l’impact initial de début d’essai et matérialisés par de fortes oscillations du signal d’effort, sont atténués par l’interposition d’un élément en élastomère dans le système d’ancrage de chaque bras de l’éprouvette. Pour finir, la méthodologie d’identification proposée est appliquée à la caractérisation du comportement viscoplastique d’un acier dual phase DP600. Les courbes d’écrouissage identifiées à partir des essais bi-axiaux ont été comparées à celles obtenues par des essais uni-axiaux pour une gamme de vitesse de déformation allant de 10- 3s-1 à 101s-1. Le DP600 présente une même sensibilité à la vitesse de déformation quelque soit la sollicitation, uni-axiale ou bi-axiale. Les lois d’écrouissage de Ludwick et de Voce, identifiées jusqu’à 30% de déformation plastique équivalente sur la base de données expérimentales constituées des essais bi-axiaux, sont relativement proches. Les différences observées entre ces courbes d’écrouissage et celles identifiées à partir des essais de traction uni-axiaux montrent tout l’intérêt de l’essai de traction bi-axiale sur éprouvette en croix. / Sheet metal forming processes are widely adopted to produce panels, tubes, profiled parts in manufacturing industry. The numerical simulation of the forming processes requires accurate constitutive models of material. In many sheet metal working operations such as stamping, hydroforming, …, large strains and intermediate strain rates can be reached under biaxial strain or stress states. The objective of this work is to show the potential of the biaxial in-plane tensile test to characterize the hardening behaviour of metal sheets up to large strain levels. By numerical investigation, an optimal cruciform shape is designed to obtain large equivalent plastic strain, up to 30%, at the central zone under equi-biaxial strain path. As expected, the initial cracks of tested specimens are always observed at the central zone. Then, quasi-static and dynamic biaxial tensile tests on in-plane cross specimens have been performed on a dedicated servo-hydraulic machine. These biaxial tensile tests have been carried out on aluminium alloy AA5086 to validate the identification methodology of hardening behaviour under biaxial loading. This alloy has been chosen since its hardening behaviour is not dependent on the strain rate. Digital Image Correlation (DIC) technique is used for strain measurement. The parameters of isotropic hardening models are identified by inverse analysis based on the finite element model of the biaxial tensile test. Three yield criteria of Mises, Hill48 and Bron and Besson are compared for the parameter identification of different hardening laws. It is shown that the hardening law identified by biaxial test is precise only if an appropriate yield function is preliminarily determined. The biaxial flow stress curve identified with Bron and Besson yield function have been found in good agreement with the experimental flow stress curve obtained from uniaxial tensile tests. For biaxial tests at intermediate strain rates, damping layers are adopted to reduce oscillations on force versus time curves. The comparison of flow stress curves, identified from quasi-static and dynamic biaxial in-plane tensile tests on the non strain rate-dependent material AA5086, validates the identification methodology of strain-rate dependent hardening models. Finally, the proposed methodology is applied to the hardening characterization of a strain-rate dependent Dual Phase steel DP600 at room temperature. Identified biaxial flow stress curves have been compared with uniaxial ones for different strain rates ( . = 10-3s-1, 10-1s-1 and 101s-1). DP600 steel exhibits the same positive strain rate sensitivity for uniaxial and biaxial strain states. The biaxial flow stress curves identified on the basis of Ludwick and Voce hardening models are close, up to equivalent plastic strains of 30%. The benefits of the proposed methodology, based on a biaxial in-plane tensile test carried out on cross specimen, are clearly shown since the hardening behaviour identified in this case for large strains (up to 30%) is very different from the one identified from uniaxial tensile test on a smaller strain range.

Metal Additive Manufacturing (AM) technologies in particular powder bed fusion processes such as Selective Laser Melting (SLM) and Direct Metal Laser Sintering (DMLS) are capable of producing a fully-dense metal components directly from computer-aided design (CAD) model without the need of tooling. This unique capability offered by metal AM has allowed the manufacture of inter-connected lattice structures from metallic materials for different applications including, medical implants and aerospace lightweight components. Despite the many promising design freedoms, metal AM still faces some major technical and design barriers in building complex structures with overhang geometries. Any overhang geometry which exceeds the minimum allowable build angle must be supported. The function of support structure is to prevent the newly melted layer from curling due to thermal stresses by anchoring it in place. External support structures are usually removed from the part after the build; however, internal support structures are difficult or impossible to remove. These limitations are in contrast to what is perceived by designers as metal AM being able to generate all conceivable geometries. Because support structures consume expensive raw materials, use a considerable amount of laser consolidation energy, there is considerable interest in design optimisation of support structure to minimize the build time, energy, and material consumption. Similarly there is growing demand of developing more advanced and lightweight cellular structures which are self-supporting and manufacturable in wider range of cell sizes and volume fractions using metal AM. The main focuses of this research is to tackle the process limitation in metal AM and promote design freedom through advanced self-supporting and low-density Triply Periodic Minimal Surface (TPMS) cellular structures. Low density uniform, and graded, cellular structures have been developed for metal AM processes. This work presents comprehensive experimental test conducted in SLM and DMLS processes using different TPMS cell topologies and materials. This research has contributed to new knowledge in understanding the manufacturability and mechanical behaviour of TPMS cellular structures with varying cell sizes, orientations and volume fractions. The new support structure method will address the saving of material (via low volume cellular structures and easy removal of powder) and saving of energy (via reduced build-time).

Cette thèse met l'accent sur la recherche scientifique pour développer une classe de procédés à hautesvitesses de déformation des tôles métalliques en alliages d'aluminium et en acier à haute résistance (AHR).Ces technologies emploient une impulsion de pression de courte durée qui propulse la tôle dans une matrice.Ces procédés sont généralement décrits comme procédés de formage par impulsion de pression (PPF). Letravail proposé dans ce mémoire de thèse a permis de surmonter trois obstacles pour l'utilisation desprocédés PPF et la fabrication à moindre coût de structures légères. Le premier obstacle a été le manque decorrélation entre formabilité et vitesses de déformation qui se développent lors d’un procédé PPF. Nous avonsproposé d’analyser la formabilité et la rupture des tôles, et de caractériser les vitesses de déformation et leurl'hétérogénéité pendant le procédé PPF. Le deuxième obstacle a été le manque de lois constitutives validéespour les métaux déformés par le procédé PPF. Nous avons étudié la microstructure et l'évolution despropriétés mécaniques durant le procédé PPF. Le troisième obstacle est le manque de modèles de formabilitéprédictifs validés pour le procédé PPF. Nous avons utilisé la méthode Marciniak-Kuczynski pour la prédictionde la formabilité de l’alliage AA5182 et de l’acier DP600 sous un large éventail de vitesses de déformation etsous différentes directions de ces vitesses. La combinaison de ces résultats de recherche permet une plusgrande capacité prédictive pour concevoir et développer des procédés PPF pour composants d’automobiledésirés à partir d'aluminium et d’acier AHR. / This thesis focuses on scientific investigation to develop and enable a class of high strain ratesheet metal forming of aluminum alloys and advanced high strength steel (AHSS). These technologiesemploy a short duration pressure‐pulse to drive sheet metal into single‐sided dies, and can generally bedescribed as pulse pressure forming (PPF) processes. The work under this thesis has overcome threetechnical barriers to using PPF processing for more cost effective lightweight vehicles. The first technicalbarrier was the lack of understanding of the interrelationship between formability and measured strainrates that develop during PPF processing. The work under this thesis investigated the formability andfracture of sheet metals during PPF, and characterized the strain rate and the strain rate heterogeneity.The second technical barrier was the lack of a validated constitutive model for lightweight materialsduring PPF processing. The work under this thesis investigated the microstructure and mechanicalproperty evolution in metals during PPF. The third technical barrier was the lack of validated andpredictive formability models for PPF processes. The work under this thesis used the Marciniak andKuczynski method of formability prediction to predict the formability of both aluminum alloy AA5182and AHSS alloy DP600 across a wide range of strain rates and strain rate directions. The combination ofthese research results permits a more predictive capacity to design and develop PPF manufacturingprocesses for a desired automotive component made from aluminum alloys and AHSS.

ABSTRACT INTERACTION BETWEEN MICRO AND NANO PATTERNED POLYMERIC SURFACES AND DIFFERENT CELL TYPES &Ouml / z&ccedil / elik, Hayriye Ph.D., Department of Biology Supervisor: Prof. Dr. Vasif Hasirci Co-Supervisor: Dr. Celestino Padeste August 2012, 139 pages Micro and nanopatterned surfaces are powerful experimental platforms for investigating the mechanisms of cell adhesion, cell orientation, differentiation and they enable significant contributions to the fields of basic cell and stem cell biology, and tissue engineering. In this study, interaction between micro and nanopatterned polymeric surfaces and different cell types was investigated. Three types of micropillars were produced by photolithography (Type 1-3), while nanometer sized pillars were produced in the form of an array by electron beam lithography (EBL). Replica of silicon masters were made of polydimethylsiloxane (PDMS). Polymeric [P(L-D,L)LA and a P(L-D,L)LA:PLGA blend] replica were prepared by solvent casting of these on the PDMS template and used in in vitro studies. The final substrates were characterized by various microscopic methods such as light microscopy, atomic force microscopy (AFM) and scanning electron microscopy (SEM). In order to investigate deformation of the nucleus in response to the physical restrictions imposed by micropillars, Type 1 and Type 2 pillars were used. These substrates were covered with pillars with different interpillar distances. While Type 1 is covered with symmetrically (in X-Y directions) distributed pillars, Type 2 pillars were distributed asymmetrically and the inter-pillar distances were increased. Nuclei deformation of five cell v types, two cancer cell lines (MCF7 and Saos-2), one healthy bone cell (hFOB1.19), one stem cell (bone marrow origined mesemchymal stem cells, BMSCs) and one standard biomaterial test cell type, (L929) fibroblasts was examined by using fluorescence microscopy and SEM. The nuclei of Saos-2 and MCF7 cells were found to be deformed most drastically. Nucleus deformation and intactness of nuclear membrane was examined by Anti- Lamin A staining. The interaction of the cells with micropillars was visualized by labelling focal adhesion complexes (FAC). Wettabilities of patterned and smooth surfaces were determined. As the patterns become denser (closer micropillars, Type 1) the hydrophobicity increased. Similar to water droplets, the cells were mostly spread at the top of the Type 1 pillars. The number of cells spread on the substrate surface was much higher on Type 2 patterned films. In order to support these qualitative findings, nucleus deformation was quantified by image analysis. Frequency of nucleus deformation was determined as the ratio of deformed to the total number of nuclei (%). In order to quantify the intensity of nuclei deformation, their circularity was evaluated. In addition to nucleus deformation, alterations in the ratio of cell area-to-nucleus area in response to micropillars were determined by image analysis. The results indicated that cancerous cells were more deformable. The qualitative microscopic evaluation and the data obtained by quantification of the nucleus and cellular deformation were in good agreement. In addition, the findings were consistent with expectations which suggest that cancerous cells are &ldquo / softer&rdquo / . In the second part of the research the force applied by the cells on arrays of micropillars with high aspect ratios (Type 3 substrates) during tugging at the pillars was investigated. Micropillars were produced using P(L-D,L)LA as well as a 60:40 blend of P(L-D,L)LA with PLGA. The blend is a material with lower stiffness than P(L-D,L)LA. The mechanical properties of the two materials were determined by tensile testing of solvent cast films. Deformation of Type 3 micropillars by the cellular tugging force of Saos-2 and L929 was studied by fluorescence and SEM microscopy, both on stiff and softer substrates. Displacements of the centers nodes of the pillars were evaluated from SEM micrographs. On the stiff surface, the two cell types bent the pillars to the same extent. On the other softer substrate (blends), however, the maximum displacements observed with Saos-2 cells were higher than the ones caused on the stiffer substrate or the ones caused by L929 cells. It is reported that stiffness of the substrate can determine stem cell lineage commitment. In order to examine the effects of change of substrate stiffness on osteogenic differentiation of BMSCs, osteopontin (OPN) expression was determined microscopically. It was found that osteogenic differentiation is enhanced when BMSCs are cultured on P(L-D,L)LA Type 3 pillars. vi In the last part of research, arrays of nanopillars whose interpillar distances systematically varied to form different fields were examined in terms of adhesion and alignment in order to determine the differential adhesion of BMSCs and Saos-2 cells. The difference in their adhesion preference on nanopillar arrays was quantified by image analysis. It was observed that BMSCs and Saos-2 cells behaved in an opposite manner with respect to each other on the fields with the highest density of nanopillars. The BMSCs avoided the most densely nanopillar covered fields and occupied the pattern free regions. The Saos-2, on the other hand, occupied the most densely nanopillar covered fields and left the pattern free regions almost unpopulated. It was also found that both BMSCs and Saos-2 cells aligned in the direction of the shorter distance between the pillars. Both BMSCs and Saos-2 cells started to align on the pillars if the distance in any direction was &gt / 1.5 &mu / m. To better understand the effects of chemical and physical cues, protein coating and material stiffness were tested as two additional parameters. After fibronectin coating, the surfaces of P(L-D,L)LA films with the highly dense pillar covered fields, which were avoided when uncoated, were highly populated by the BMSC. Similarly, decreasing the stiffness of a surface which was normally avoided by the BMSCs made it more acceptable for the cells to attach.

Chemotherapy is one of the common treatments in cancer therapy. The effectiveness of chemotherapy is limited by several factors one of which is the emergence of multidrug resistance (MDR). MDR is caused by the activity of diverse ATP binding cassette (ABC) transporters that pump drugs out of the cells. There are several drugs which have been used in treatment of cancer. One of them is doxorubicin that intercalates and inhibits DNA replication. However, doxorubicin has been found to cause development of MDR in tumors. It has been reported that there is a correlation between multidrug resistance and invasiveness of cancer cells. Vimentin is a type III intermediate filament protein that is expressed frequently in epithelial carcinomas correlating with invasiveness and also poor prognosis of cancer. There are several studies that have shown the connection between expression level of vimentin and invasiveness. In this study, MCF-7 cell line (MCF-7/S), which is a model cell line for human mammary carcinoma, and doxorubicin resistant MCF-7 cell line (MCF-7/Dox) were used. The resistant cell line was previously obtained by stepwise selection in our laboratory. The main purpose of this study was to investigate changes of metastatic behaviour in MCF-7/Dox cell line, after transient silencing of vimentin gene by siRNA. In conclusion, down-regulation of vimentin gene expression in MCF-7/Dox cell lines was expected to change the characteristics in migration and invasiveness shown by migration and invasion assays.