Improved cytotoxicity testing of magnesium materials

Metallic magnesium (Mg) and its alloys are highly suitable for medical applications as biocompatible and biodegradable implant materials. Magnesium has mechanical properties similar to bone, stimulates bone regeneration, is an essential non-toxic element for the human body and degrades completely within the body environment. In consequence, magnesium is a promising candidate as implant material for orthopaedic applications. Protocols using the guideline of current ISO standards should be carefully evaluated when applying them for the characterization of the cytotoxic potential of degradable magnesium materials. For as-cast material we recommend using 10 times more extraction medium than recommended by the ISO standards to obtain reasonable results for reliable cytotoxicity rankings of degradable materials in vitro. In addition primary isolated human osteoblasts or mesenchymal stem cells should be used to test magnesium materials.     

Light‐Controlled Reversible Manipulation of Microgel Particle Size Using Azobenzene‐Containing Surfactant

The light‐induced reversible switching of the swelling of microgel particles triggered by photo‐isomerization and binding/unbinding of a photosensitive azobenzene‐containing surfactant is reported. The interactions between the microgel (N‐isopropylacrylamide, co‐monomer: allyl acetic acid, crosslinker: N,N′‐methylenebisacrylamide) and the surfactant are studied by UV‐Vis spectroscopy, dynamic and electrophoretic light scattering measurements. Addition of the surfactant above a critical concentration leads to contraction/collapse of the microgel. UV light irradiation results in trans‐cis isomerization of the azobenzene unit incorporated into the surfactant tail and causes an unbinding of the more hydrophilic cis isomer from the microgel and its reversible swelling. The reversible contraction can be realized by blue light irradiation that transfers the surfactant back to the more hydrophobic trans conformation, in which it binds to the microgel. The phase diagram of the surfactant‐microgel interaction and transitions (aggregation, contraction, and precipitation) is constructed and allows prediction of changes in the system when the concentration of one or both components is varied. Remote and reversible switching between different states can be realized by either UV or visible light irradiation.     

Toxikologie der synthetischen Antioxidantien BHA und BHT im Vergleich mit dem natürlichen Antioxidans Vitamin E

The toxicology of the food preservatives butylhydroxyanisole (BHA) and butylhydroxytoluene (BHT) as well as the naturally occurring vitamin E (α-tocopherol) is described. In high dosages all three compounds induce in animals impairment of blood clotting, which can be explained by an antagonism with vitamin K. Specific toxic effects to the lung have only been observed with BHT. The other described toxic effects of BHA and BHT are less characteristic and often occur only after high dosage and long-term treatment. However, BHA induces in animals tumours of the forestomach, which are dose dependent, whereas BHT induces liver tumours in long-term experiments. Because there is no indication of genotoxicity of BHA and BHT, all published findings agree with the fact that BHA and BHT are tumour promoters. In contrast to BHA and BHT, vitamin E is not carcinogenic. On the other hand, all three antioxidants have also anticarcinogenic properties. The intake of the necessary high doses as for these effects are, however, contraindicated with BHA and BHT because of their carcinogenic effects. The present overview concludes that the concentrations of BHA and BHT nowadays used in food, drugs and cosmetics are probably harmless. In addition, vitamin E can also be used in higher doses without the occurrence of adverse effects.     

One‐Step Formulation of Protein Microparticles with Tailored Properties: Hard Templating at Soft Conditions

Formulation of therapeutic proteins into particulate forms is a main strategy for site‐specific and prolonged protein delivery as well as for protection against degradation. Precise control over protein particle size, dispersity, purity, as well as mild preparation conditions and minimal processing steps are highly desirable. It is, however, hard to fit all these criteria with conventional preparation techniques. Here a one‐step hard‐templating synthesis of microparticles composed of functional, non‐denatured protein is reported. The method is based on filling porous CaCO₃ microtemplates with the protein near to its isoelectric point (pI) followed by pH‐ or EDTA‐mediated dissolution of the tempplates. In principle, a wide variety of proteins can be converted into microparticles using this approach. The main requirement is an overlap of the protein insolubility and a template solubility for a certain parameter (here pH or EDTA). Here the formulation of insulin particles is studied in detail and it is shown that particles consisting of high molecular weight protein (catalase) can also be prepared. In this context, the synthesis of CaCO₃ templates with controlled size, the mechanism of the protein microparticle formation and mechanical properties of the microparticles are discussed. For the first time, the fabrication of mesoporous monodispersed CaCO₃ microtemplates with identical porocity but tuned diameter from 3 to 20 μm is demonstrated. The protein particle diameter can be adjusted by choosing the appropriate template size that is critical for successful pulmonary delivery of insulin. As a first step towards insulin delivery, the in vitro release of insulin at physiological conditions is studied.     

Characteristics of Bi-metallic Interfaces Formed During Direct Energy Deposition Additive Manufacturing Processing

Metallurgical and Materials Transactions B - Various additive manufacturing processes are being evaluated to reduce the time and cost for fabrication of low volume, complex, and multifunctional...     

Platelet-Released Growth Factors Influence Wound Healing-Associated Genes in Human Keratinocytes and Ex Vivo Skin Explants

Platelet-released growth factors (PRGFs) or other thrombocyte concentrate products, e.g., Platelet-Rich Fibrin (PRF), have become efficient tools of regenerative medicine in many medical disciplines. In the context of wound healing, it has been demonstrated that treatment of chronic or complicated wounds with PRGF or PRF improves wound healing in the majority of treated patients. Nevertheless, the underlying cellular and molecular mechanism are still poorly understood. Therefore, we aimed to analyze if PRGF-treatment of human keratinocytes caused the induction of genes encoding paracrine factors associated with successful wound healing. The investigated genes were Semaphorin 7A (SEMA7A), Angiopoietin-like 4 (ANGPLT4), Fibroblast Growth Factor-2 (FGF-2), Interleukin-32 (IL-32), the CC-chemokine-ligand 20 (CCL20), the matrix-metalloproteinase-2 (MMP-2), the chemokine C-X-C motif chemokine ligand 10 (CXCL10) and the subunit B of the Platelet-Derived Growth Factor (PDGFB). We observed a significant gene induction of SEMA7A, ANGPLT4, FGF-2, IL-32, MMP-2 and PDGFB in human keratinocytes after PRGF treatment. The CCL20- and CXCL10 gene expressions were significantly inhibited by PRGF therapy. Signal transduction analyses revealed that the PRGF-mediated gene induction of SEMA7A, ANGPLT4, IL-32 and MMP-2 in human keratinocytes was transduced via the IL-6 receptor pathway. In contrast, EGF receptor signaling was not involved in the PRGF-mediated gene expression of analyzed genes in human keratinocytes. Additionally, treatment of ex vivo skin explants with PRGF confirmed a significant gene induction of SEMA7A, ANGPLT4, MMP-2 and PDGFB. Taken together, these results describe a new mechanism that could be responsible for the beneficial wound healing properties of PRGF or related thrombocytes concentrate products such as PRF.     

Chirality of synergistic sex pheromone components of the western hemlock looperLambdina fiscellaria lugubrosa (HULST) (Lepidoptera: Geometridae)

Bakers' yeast reduction of (2E)-3-(2-furanyl)-2-methyl-2-propenal yielded the synthetic intermediate, (2S)-3-(2-furanyl)-2-methylpropanol, of high chiral purity (>97% ee) for the synthesis of the enantiomers of 2,5-dimethylheptadecane and 7-methylheptadecane, two synergistic sex pheromone components of the western hemlock looper (WHL),Lambdina fiscellaria lugubrosa Hulst. In electrophysiological bioassays, (7S)- but not (7R)-7-methylheptadecane elicited strong antennal responses by male WHL antennae. In field trapping experiments, addition of (7S)- but not (7R)-7-methylheptadecane to (5R,11S)-5,11-dimethylheptadecane, the major sex pheromone component of WHL, increased attraction. Attraction to (5R,11S)-5,11-dimethylheptadecane in combination with (7S)-7-methyiheptadecane was further enhanced by the addition of (5S)- but not (5R)-2,5-dimethylheptadecane. Similarly, attraction to (5R,11S)-5,11-dimethylheptadecane combined with (5S)-2,5-dimethylheptadecane increased when 7S- but not (7R)-7-methylheptadecane was added as a third component. We conclude that (7S)-7-methylheptadecane and (5S)-2,5-dimethylheptadecane are the synergistic sex pheromone components of WHL. The synthetic methodology described is applicable to the synthesis of chiral methyl-branched pheromones in other orders of the Insecta, particularly Coleoptera, Diptera and Orthoptera.