Novel biodegradable Round Window Disks for inner ear delivery of dexamethasone.

Drug delivery to the inner ear is an important and very challenging field. The cochlea is protected by several barriers that need to be overcome in the drug delivery process. Local drug delivery can avoid undesirable side effects arising from systemic drug delivery. We developed a biodegradable dexamethasone-loaded Round Window (RW) Disk based on poly(D,L-lactic-co-glycolic acid) (PLGA) for local drug therapy to the inner ear by RW membrane administration by a film-casting method. The optimal drying time was characterized by thermogravimetric analysis and differential scanning calorimetry. In addition, the mass and polymer degradation over time of drug release was measured in vitro showing a total mass loss of 70% after 3 weeks. Dexamethasone release was determined by a RW model setup using a polyethylene terephthalate membrane. We achieved a controlled release over 52 days. Ex vivo implantation of a RW Disk onto a guinea pig RW membrane indicated well-fitting properties of the drug delivery device leading to a close surface contact with the membrane and the successful proof of concept. The developed RW Disks could be new and promising drug delivery device to achieve effective local drug delivery to the inner ear for an extended time.

Assessment of the applicability of HLB values for natural phospholipid emulsifiers for preparation of stable emulsions.

Natural phospholipid (PL) excipients are native, biocompatible and relatively inexpensive alternatives to synthetic emulsifiers. A well-known PL excipient is lecithin, which primarily contains phosphatidylcholine (PC) and (depending on the purity grade) also contains a well-defined mixture of other PLs with a fatty acid composition, which reflects their natural source. Since all of these lipid species are emulsifiers, natural PLs can be considered as a mixture of (co-) emulsifiers. Many different HLB values for lecithins are given in the literature, which is why this needs to be clarified. To assess this, HLB values of thirteen different plant derived PLs differing in PC content were determined using a centrifugation stress method to determine the relative stability of an emulsion with the respective emulsifier and different oil phases. It could be shown that the studied PLs can be characterized by a broad HLB range, which may be linked to the composition of the PLs and the oil used. In order to emphasize the results of the HLB determination, it could be demonstrated that stable emulsions could be prepared with a wide range of oils using the plant-based PLs and that the preparation method of the emulsions is important in order to obtain stable emulsions. Therefore, assigning a specific exact HLB value to natural PLs instead of a wider range is inappropriate. The broad HLB ranges indicate the suitability of the studied PL emulsifiers for the preparation of oil-in-water emulsions for a wide range of oils: It is recommended to experimentally evaluate the suitability of these natural emulsifiers for the preparation of stable emulsions and to benefit from the wide range of HLB values of these emulsifiers instead of relying on inaccurate and confusing HLB values in the literature.

Cellular compatibility of highly degradable bioactive ceramics for coating of metal implants.

Resorbable ceramics can promote the bony integration of implants. Their rate of degradation should ideally be synchronized with bone regeneration. This study examined the effect of rapidly resorbable calcium phosphate ceramics 602020, GB14, 305020 on adherence, proliferation and morphology of human bone-derived cells (HBDC) in comparison to ß-TCP. The in vitro cytotoxicity was determined by the microculture tetrazolium (MTT) assay. HBDC were grown on the materials for 3, 7, 11, 15 and 19 days and counted. Cell morphology, cell attachment, cell spreading and the cytoskeletal organization of HBDC cultivated on the substrates were investigated using laser scanning microscopy and environmental scanning electron microscopy. All substrates supported sufficient cellular growth for 19 days and showed no cytotoxicity. On each material an identical cell colonisation of well communicating, polygonal, vital cells with strong focal contacts was verified. HBDC showed numerous well defined stress fibres which give proof of well spread and strongly anchored cells. Porous surfaces encouraged the attachment and spreading of HBDC. Further investigations regarding long term biomaterial/cell interactions in vitro and in vivo are required to confirm the utility of the new biomaterials.

Fabrication and characterization of a biomimetic composite scaffold for bone defect repair.

For successful bone tissue engineering, scaffolds with tailored properties are a basic requirement. The combination of different available materials not only appears to be desirable but also very challenging. In this study, a composite material consisting of hydroxyapatite and collagen was produced by a biomimetic precipitation method and characterized by X-ray diffraction (XRD) and thermogravimetry (TGA). Subsequently, a suspension-quick-freezing and lyophilization method was used to incorporate the hydroxyapatite into a polymeric matrix consisting of collagen and chitosan. Before physicochemical characterization, the highly porous scaffolds were consolidated by a dehydrothermal treatment (DHT). The main attention was focused on the particle size of hydroxyapatite, which should be in the nanometer range. This is relevant to achieve a homogeneous resorption of the material by osteoclasts. Small-angle X-ray scattering (SAXS), atomic force microscopy (AFM), and environmental scanning electron microscopy (ESEM) were used to evaluate the outcome. The results suggest a successful polymeric embedding of nanoscaled hydroxyapatite particles into the matrix of the spongy construct. (c) 2010 Wiley Periodicals, Inc. J Biomed Mater Res, 2010.

Silicon nanowire oxidation: the influence of sidewall structure and gold distribution.

The oxidation behavior of Si nanowires (SiNWs) grown by the gold (Au) catalyzed vapor-liquid-solid (VLS) growth process in an electron beam evaporation (EBE) reactor is studied. The VLS SiNWs exhibit hexagonal shape with essentially {112} facets where each facet shows a saw-tooth faceting itself, consisting of alternating {111} and {113} facets. Depending on growth temperatures (450-750 degrees C) and evaporation currents (40-80 mA) that determine the silicon vapor supply, this facet formation is more or less pronounced. The diffusion of Au atoms on the faceted SiNW surfaces and the formation of Au nanoparticles on the SiNW facets during growth and during ex situ annealing are studied. Upon diffusion, the Au atoms agglomerate and form Au nanoparticles that preferably arrange themselves on {113} facets. Upon annealing in air at temperatures between 800 and 950 degrees C the gold nanoparticles agglomerate further and form bigger particles of a few tens of nm in diameter that reside at the interface between the growing silica (SiO(2)) layer and the SiNW itself, which in turn shrinks during SiNW oxidation. The oxide layer thickness and the oxide appearance depend on the annealing conditions (time and temperature) and systematically varied oxidation processing is described in this paper as investigated by cross-sectional transmission electron microscopy (TEM) including high resolution studies as well as scanning electron microscopy (SEM) studies. Our results strongly suggest that the SiNWs can be fully oxidized, thus forming silica NWs that can either keep their initial shape or, under certain annealing conditions, do not keep their initial wire shape but assume a bamboo-like shape that forms most likely as a result of locally high stresses that are related to nanocrack formation. The nanocracks form in the growing oxide layer mediated by the presence of Au nanoparticles that yield gold-enhanced SiNW oxidation and thus a faster oxidation rate.

[Mechanical changes in bone after roentgen irradiation with low dosage]. / Mechanische Veränderungen des Knochens nach Röntgenbestrahlung mit niedrigen Dosen.

We investigated the micromechanical properties using doses from 1 up to 7 Gray and could observe a roughening on the surface of the bone material in the microscopic range by scanning acoustic microscopic measurements. In addition, a preceding irradiation promoted an extension of microcracks during the polishing process indicating an embrittlement. After irradiation and removal of the surface layer, the SAM measurements indicate a preferential increasing of hardness of softer regions. These results are consistent with our measurements by environmental scanning electron microscopy.