Exploring the Biomaterial-Induced Secretome: Physical Bone Substitute Characteristics Influence the Cytokine Expression of Macrophages

In addition to their chemical composition various physical properties of synthetic bone substitute materials have been shown to influence their regenerative potential and to influence the expression of cytokines produced by monocytes, the key cell-type responsible for tissue reaction to biomaterials in vivo. In the present study both the regenerative potential and the inflammatory response to five bone substitute materials all based on β-tricalcium phosphate (β-TCP), but which differed in their physical characteristics (i.e., granule size, granule shape and porosity) were analyzed for their effects on monocyte cytokine expression. To determine the effects of the physical characteristics of the different materials, the proliferation of primary human osteoblasts growing on the materials was analyzed. To determine the immunogenic effects of the different materials on human peripheral blood monocytes, cells cultured on the materials were evaluated for the expression of 14 pro- and anti-inflammatory cytokines, i.e., IL-6, IL-10, IL-1β, VEGF, RANTES, IL-12p40, I-CAM, IL-4, V-CAM, TNF-α, GM-CSF, MIP-1α, Il-8 and MCP-1 using a Bio-Plex^® Multiplex System. The granular shape of bone substitutes showed a significant influence on the osteoblast proliferation. Moreover, smaller pore sizes, round granular shape and larger granule size increased the expression of GM-CSF, RANTES, IL-10 and IL-12 by monocytes, while polygonal shape and the larger pore sizes increased the expression of V-CAM. The physical characteristics of a bone biomaterial can influence the proliferation rate of osteoblasts and has an influence on the cytokine gene expression of monocytes in vitro. These results indicate that the physical structure of a biomaterial has a significant effect of how cells interact with the material. Thus, specific characteristics of a material may strongly affect the regenerative potential in vivo.     

Photo-vulcanization using thiol-ene chemistry: Film formation,morphology and network characteristics of UV crosslinked rubber latices

The photo-vulcanization with versatile thiol-ene chemistry represents an innovative approach to crosslink diene-rubber materials both in latex and in solid film state. In this work, the structure of elastomer-based thiol-ene networks and the morphology after film formation are studied in detail using electron microscopic techniques, atomic force microscopy and multiple-quantum solid-state NMR spectroscopy. Additionally, film formation properties and corresponding macroscopic properties of photo-vulcanized natural rubber (NR) latex and its synthetic counterpart, isoprene rubber (IR) latex, are determined in dependence on the curing procedure (pre- and post-vulcanization). The results reveal that thiol-ene cured elastomers comprise homogenously distributed crosslinks with a low amount of short chain defects. Whilst photochemically pre-cured NR latex particles provide coherent films, the film formation and mechanical properties of IR are strongly governed by the crosslink density of the latex particles. In film state, photo-vulcanization promotes narrow crosslink distributions and excellent tensile properties of both NR and IR.     

An effective medium model for TM-polarized nonlinear guided wavesin multilayer systems

An effective medium model for TM-polarized nonlinear guided waves is derived. It is shown that a periodic multifilm configuration can be described as a single film with effective dielectric tensor components. Unlike in the TE-case these tensor components depend on the local fields and hence cannot be defined globally. Numerical investigations indicate that the effective medium model can be applied for most situations     

Analysis of metal-clad anti resonant reflecting optical waveguidefor polarizer applications

The dispersion and attenuation characteristics of an ARROW (antiresonant reflecting optical waveguide) with and without thin metal layers deposited on the outside of the interference cladding layer are investigated. These thin metal layers improve the polarization-selective performance of the ARROW considerably. A simple analytical expression to calculate the optimal thickness of the metal layer is derived     

Polarization splitter based on antiresonant reflecting opticalwaveguides

We propose the first polarization splitter based on antiresonant optical waveguides (ARROW's). The three air core structure is built up of two moveable outer cladding layers and two fixed inner cladding layers. The moveability of both outer cladding layers makes micromechanical switching of the polarized light between two output channels possible. The polarization discrimination is realized through thin metal films deposited on the outermost surfaces of the outer cladding layers. The extinction ratios of channels 1 and 3 as a function of the thickness of all cladding layers are calculated. We found that for extinction ratios below -20 dB thickness fluctuations smaller than ±15 mm are allowed     

Intermittent Fasting Primes the Tumor Microenvironment and Improves Nanomedicine Delivery in Hepatocellular Carcinoma

Fasting has many health benefits, including reduced chemotherapy toxicity and improved efficacy. It is unclear how fasting affects the tumor microenvironment (TME) and tumor-targeted drug delivery. Here the effects of intermittent (IF) and short-term (STF) fasting are investigated on tumor growth, TME composition, and liposome delivery in allogeneic hepatocellular carcinoma (HCC) mouse models. To this end, mice are inoculated either subcutaneously or intrahepatically with Hep-55.1C cells and subjected to IF for 24 d or to STF for 1 d. IF but not STF significantly slows down tumor growth. IF increases tumor vascularization and decreases collagen density, resulting in improved liposome delivery. In vitro, fasting furthermore promotes the tumor cell uptake of liposomes. These results demonstrate that IF shapes the TME in HCC towards enhanced drug delivery. Finally, when combining IF with liposomal doxorubicin treatment, the antitumor efficacy of nanochemotherapy is found to be increased, while systemic side effects are reduced. Altogether, these findings exemplify that the beneficial effects of fasting on anticancer therapy outcomes go beyond modulating metabolism at the molecular level.     

Towards a comprehensive proteome of normal and malignant human colon tissue by 2-D-LC-ESI-MS and 2-DE proteomics and identification of S100A12 as potential cancer biomarker

The aim of this study was to characterize the proteome of normal and malignant colonic tissue. We previously studied the colon proteome using 2‐DE and MALDI‐MS and identified 734 proteins (Roeßler, M., Rollinger, W., Palme S., Hagmann, M.‐L., et al.., Clin. Cancer Res. 2005, 11, 6550–6557). Here we report the identification of additional colon proteins from the same set of tissue samples using a complementary nano‐flow 2‐D‐LC‐ESI‐MS. In total, 484 proteins were identified in colon. Of these, 252 had also been identified by the 2‐DE/MALDI‐MS approach, whereas 232 proteins were unique to the 2‐D‐LC‐ESI‐MS analysis. Comparing protein expression in neoplastic and normal colon tissue indicated elevated expression of several proteins in colorectal cancer, among them the well established tumor marker carcinoembryonic antigen, as well as calnexin, 40S ribosomal protein S15a, serpin H1, and S100A12. Overexpression of these proteins was confirmed by immunoblotting. Serum levels of S100A12 were determined by ELISA and were found to be strongly elevated in colorectal cancer patients compared to healthy individuals. We conclude, that 2‐D‐LC‐ESI‐MS is a powerful approach to identify and compare protein profiles of tissue samples, that it is complementary to 2‐DE/MALDI‐MS approaches and has the potential to identify novel biomarkers.     

Dye and polymer based light sensor for tag integration

In this work we present a light sensor for tag integration based on the principle of a dye sensitized solar cell, using a flexible substrate and a polymer electrolyte. These features make an integration of the light sensor into current smart label fabrication processes possible. A printable light sensor combined with novel conductive polymers could solve reliability issues resulting from bonding processes. The components of the light sensor were chosen in a way to enable screen print production. The dye Ruthenium 535-bis-TBA has been used as active dye and Iodolyte AN-50 by Solaronix and PEDOT/PSS by H.C. Starck have been used as liquid and polymer electrolyte respectively. In order to prepare the liquid electrolyte for tag integration it has been gelatinized by addition of silica gel. Depending on the amount of silica gel different stiffness levels have been achieved. The functional layers have been deposited first on glass substrate and then on KAPTON foil by Du Pont. The polymer has been used as flexible substrate. Special care has been taken regarding the preparation of the transparent electrode. The transparent conductive oxide (TCO) indium tin oxide (ITO), which has been used as transparent electrode, has to be cured at elevated temperatures on the polymer substrate. A complete process flow for an integrated light sensor is being described in this work.