Surface Functionalization and Patterning by Multifunctional Resorcinarenes.

Plant phenolic compounds and catecholamines have been widely used to obtain substrate-independent precursor nanocoatings and adhesives. Nevertheless, there are downsides in using such phenolic compounds for surface modification such as formation of nonuniform coatings, need for multistep modification, and restricted possibilities for postfunctionalization. In this study, inspired by a strong binding ability of natural polyphenols found in plants, we used three different macrocyclic polyphenols, known as resorcin[4]arenes, to modify the surface of different substrates by simple dip-coating into the dilute solution of these compounds. Eight hydroxyl groups on the large rim of these resorcin[4]arenes provide multiple anchoring points to the surface, whereas the lower rim decorated with different appending groups introduces the desired chemical and physical functionalities to the substrate's surface. Deposition of a uniform and transparent resorcinarene layer on the surface was confirmed by several surface characterization techniques. Incubation of the modified substrates in different environments indicated that the stability of the resorcinarene layer was dependent on the type of substrate and the pH value. The most stable resorcinarene layer was formed on amine-functionalized substrates. The surface was modified with alkenyl functional groups in one step using a resorcinarene compound possessing four alkenyl appending groups on its small rim. Thiol-ene photoclick chemistry was used to site-selectively postfunctionalize the surface with hydrophilic and hydrophobic micropatterns, which was confirmed by X-ray photoelectron spectroscopy and time-of-flight secondary ion mass spectrometry. Thus, we demonstrate that resorcin[4]arenes extend the scope of applications of plant polyphenol and mussel-inspired precursors to tailor-made multifunctional nanocoatings, suitable for a variety of potential applications in biotechnology, biology, and material science.

Flexible fluidic microchips based on thermoformed and locally modified thin polymer films.

This paper presents a fundamentally new approach for the manufacturing and the possible applications of lab on a chip devices, mainly in the form of disposable fluidic microchips for life sciences applications. The new technology approach is based on a novel microscale thermoforming of thin polymer films as core process. The flexibility not only of the semi-finished but partly also of the finished products in the form of film chips could enable future reel to reel processes in production but also in application. The central so-called 'microthermoforming' process can be surrounded by pairs of associated pre- and postprocesses for micro- and nanopatterned surface and bulk modification or functionalisation of the formed films. This new approach of microscale thermoforming of thin polymer film substrates overlaid with a split local modification of the films is called 'SMART', which stands for 'substrate modification and replication by thermoforming'. In the process, still on the unformed, plane film, the material modifications of the preprocess define the locations where later, then on the spatially formed film, the postprocess generates the final local modifications. So, one can obtain highly resolved modification patterns also on hardly accessible side walls and even behind undercuts. As a first application of the new technology, we present a flexible chip-sized scaffold for three dimensional cell cultivation in the form of a microcontainer array. The spatially warped container walls have been provided with micropores, cell adhesion micropatterns and thin film microelectrodes.

The three-dimensional cultivation of the carcinoma cell line HepG2 in a perfused chip system leads to a more differentiated phenotype of the cells compared to monolayer culture.

We describe a polymer chip with a grid-like architecture that it is intended for the three-dimensional cultivation of cells with an active nutrient and gas supply. The chip is typically made from polymethyl methacrylate or polycarbonate but can also be manufactured from biodegradable polymers, such as poly(lactic-co-glycolic acid). Different designs of the chip can be realized. In this study, we evaluated a chip with 506 microcontainers of the size of 300 x 300 x 300 microm that are capable of housing up to 6 million cells, and its suitability as a tissue-specific culture system for the carcinoma cell line HepG2 instead of primary liver cells. Related to an earlier study, where we could show the principal suitability of the system for rat primary cells, we here investigated the system's suitability for the human carcinoma cell line HepG2. The carcinoma cells were used in two different types of chip-containing bioreactors. By confocal laser scanning microscopy, we could show that cellular integrity in the chip culture was maintained and that there were no signs of apoptosis as confirmed by the absence of K18 fragmentation. Gene expression analysis of some liver-specific genes revealed a significantly higher expression of the phase II metabolism genes uridine-diphosphate- glucosyl-transferase (UGT1A1) and glutathione-S-transferase (GSTpi1) as a marker. Therefore, we conclude that by using a three-dimensional instead of a conventional monolayer culture system, hepatocellular carcinoma cells display a phenotype that resembles more closely the tissue of origin.

3D tissue culture substrates produced by microthermoforming of pre-processed polymer films.

We describe a new technology based on thermoforming as a microfabrication process. It significantly enhances the tailoring of polymers for three dimensional tissue engineering purposes since for the first time highly resolved surface and bulk modifications prior to a microstructuring process can be realised. In contrast to typical micro moulding techniques, the melting phase is avoided and thus allows the forming of pre-processed polymer films. The polymer is formed in a thermoelastic state without loss of material coherence. Therefore, previously generated modifications can be preserved. To prove the feasibility of our newly developed technique, so called SMART = Substrate Modification And Replication by Thermoforming, polymer films treated by various polymer modification methods, like UV-based patterned films, and films modified by the bombardment with energetic heavy ions, were post-processed by microthermoforming. The preservation of locally applied specific surface and bulk features was demonstrated e.g. by the selective adhesion of cells to patterned microcavity walls.

Patterned polymer surfaces for cell culture applications.

We studied the physico/chemical effects of deep UV irradiation of polystyrene, PMMA and polycarbonate with respect to cell adhesion and protein immobilization. Photochemical modifications of the polymer surfaces yielded unstable peroxides and carboxylic acid groups. Patterned enzyme and antibody adsorbates were realized by coupling via carbodiimid activation of the COOH-moities. Hepatoma cells (HepG2) and fibroblasts (L929) adhered in the presence of serum proteins in the culture medium on the irradiated regions of the substrate without any further treatment.

[Two unexpected cases of hepatobiliary fascioliasis in Dakar (Senegal)]. / Deux observations inattendues de distomatose hépato-biliaire à Dakar (Sénégal).

The authors report two hepatobiliary distomatosis cases on patients living in Senegal and Cape Verde islands. No similar case has been reported in Senegal so far. The first case was a 41 years old woman who presented enlarged, painful liver with hypereosinophilia. There was no fever. Ultrasound and CT Scan demonstrated the presence of three poorly limited and heterogeneous masses, located on the liver right lobe. The percutaneous biopsy was not suggestive. Because of the fear ofhepatocellular carcinoma, a hepatectomy was performed and eosinophilic abcesses were found in the piece of resected liver with Fasciola eggs. The second case was a 32 years old man who presented a febrile enlarged liver with hypereosinophilia. Ultrasound revealed an heterogenous process of the liver fourth segment Serology study using Fasciola hepatica antigen was positive. The treatment with Praziquantel was successful. The clinical and epidemiological inquiry in both cases has found stays in Cape Verde islands before the disease. This was consistent with a contamination in that region. In both cases either F hepatica or F gigantica could be responsible since the serological tests are not able to differentiate these two species. Parasitic hepatopathies should be recognised particularly when a painful liver process is associated to hypereosinophilia. The serological tests will help to establish the diagnosis