Computational modelling of void growth in swelled hydrogels

The nature and the large notable distinguishing features of polymeric gels explain their pervasive use as biomaterials in both regenerative medicine and tissue engineering. With regard to their biocompatibility, their ability to withstand large deformation and their significant capacity of solvent absorption, these biomaterials are often selected owing to their versatile mechanical properties and especially the closeness to soft biological tissues, amongst others. A finite-strain theory for the study of the overall behaviour of a porous polymeric gel where microvoids are present is presented. The swollen polymeric gel is modeled as a two-component body composed of two incompressible components, namely, an elastic porous polymer imbibed with a solvant. The chemical equilibrium is assumed to be preponderate at the interface between the porous polymer and the environment where the chemical potential of the solvent is fixed. The initially dry porous polymer undergoes large deformation induced by absorption of a solvent from the environment and mechanical loading. In this paper an attempt is made towards obtaining an estimation of the macroscopic responses of the swollen porous polymer to prescribed proportional loadings. To this end, a two-level representation of the material at hand for which the Representative Volume Element (RVE) imbibed with a solvent is a simple axisymmetric cylinder composed of a homogeneous matrix surrounding a spherical void, is considered. The computational study addresses the situation where the RVE is subjected to prescribed axial and lateral overall stresses under conditions of constant overall stress triaxiality. For fixed values of the Flory-Huggins parameter and the nominal concentration of the solvent, the overall stress-strain behaviour of the RVE model, the influence of the initial porosity, and the prescribed stress triaxiality ratio have been outlined

Specific antibacterial activity of copper alloy touch surfaces in five long-term care facilities for older adults

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Biocompatibility of sol-gel hydroxyapatite-titania composite and bilayer coatings

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CFTR-KO pigs exhibit altered bone microarchitecture at birth

International audienceBackground: People with cystic fibrosis exhibit growth defects and brittle bones. That observation has been attributed, in part, to malnutrition and chronic pulmonary inflammation. We tested the hypothesis that disrup-tion of the cystic fibrosis transmembrane conductance regulator (Cftr) gene directly affects bone microarchitecture and integrity by studying bone of newborn Cftr-/- pigs. Methods: We examined femoral cortical and trabecular bones of Cftr-/- pigs less than 24 hours after birth using microcomputed tomography (mCT, Skyscan 1076, Bruker). Scans were performed with the following settings: tube voltage, 80 kV; tube current, 0.125 mA; and voxel size, 17 x 17 x 17 mm (x, y, z). Three-dimensional images were reconstructed and analysed using the NRecon GPU version and CTAn (Bruker) software programs, respectively. The cortical bone porosity and structure were defined using a 3.4 mm wide region centered on the middle of the femur. A total of 37 newborn Cftr-/- piglets (24 males and 13 females) and 18 newborn Cftr+/+ piglets (8 males and 10 females) was subjected to mCT scan. Results: Compared to newborn Cftr+/+ pig controls, Cftr-/- femoral bone exhibited significantly lower total volume (TV), bone volume (BV) and bone volume density (BV/TV) but only in females. However, the Cftr-/- bone mineral density (BMD) in trabecular and cortical tissues was signifi-cantly reduced in both sexes, compared to Cftr+/+ piglets. Interestingly, focusing at the porosity of cortical bone in Cftr-/- pigs as a determinant of bone fragility associated with high fracture risk, we observed higher closed porosity with a marked increase of closed pore surface in cortical bone of Cftr-/- pigs (+18.7% for males and +48% for females). These results suggest a lower bone remodelling, lower interconnectivity within the vascular network, and increased bone fragility in Cftr-/- animals. No significant difference was observed in the open cortical porosity, whatever the gender. Conclusion: Altogether, these data highlight the critical regulatory role of CFTR in bone development and maintenance, and suggest that some bone defects in people with cystic fibrosis are likely primary. Acknowledgment: This work was, in part, supported by the Associa-tion French Vaincre la Mucoviscidose

CFTR-KO pigs exhibit altered bone microarchitecture at birth

International audienceBackground: People with cystic fibrosis exhibit growth defects and brittle bones. That observation has been attributed, in part, to malnutrition and chronic pulmonary inflammation. We tested the hypothesis that disrup-tion of the cystic fibrosis transmembrane conductance regulator (Cftr) gene directly affects bone microarchitecture and integrity by studying bone of newborn Cftr-/- pigs. Methods: We examined femoral cortical and trabecular bones of Cftr-/- pigs less than 24 hours after birth using microcomputed tomography (mCT, Skyscan 1076, Bruker). Scans were performed with the following settings: tube voltage, 80 kV; tube current, 0.125 mA; and voxel size, 17 x 17 x 17 mm (x, y, z). Three-dimensional images were reconstructed and analysed using the NRecon GPU version and CTAn (Bruker) software programs, respectively. The cortical bone porosity and structure were defined using a 3.4 mm wide region centered on the middle of the femur. A total of 37 newborn Cftr-/- piglets (24 males and 13 females) and 18 newborn Cftr+/+ piglets (8 males and 10 females) was subjected to mCT scan. Results: Compared to newborn Cftr+/+ pig controls, Cftr-/- femoral bone exhibited significantly lower total volume (TV), bone volume (BV) and bone volume density (BV/TV) but only in females. However, the Cftr-/- bone mineral density (BMD) in trabecular and cortical tissues was signifi-cantly reduced in both sexes, compared to Cftr+/+ piglets. Interestingly, focusing at the porosity of cortical bone in Cftr-/- pigs as a determinant of bone fragility associated with high fracture risk, we observed higher closed porosity with a marked increase of closed pore surface in cortical bone of Cftr-/- pigs (+18.7% for males and +48% for females). These results suggest a lower bone remodelling, lower interconnectivity within the vascular network, and increased bone fragility in Cftr-/- animals. No significant difference was observed in the open cortical porosity, whatever the gender. Conclusion: Altogether, these data highlight the critical regulatory role of CFTR in bone development and maintenance, and suggest that some bone defects in people with cystic fibrosis are likely primary. Acknowledgment: This work was, in part, supported by the Associa-tion French Vaincre la Mucoviscidose

Bio-guided isolation of methanol-soluble metabolites of common spruce (Picea abies) bark by-products and investigation of their dermo-cosmetic properties

Common spruce (Picea abies L.) is a fast-growing coniferous tree, widely used in several countries for the production of sawn wood, timber and pulp. During this industrial exploitation, large quantities of barks are generated as waste materials. The aim of this study was the bio-guided investigation and the effective recovery of methanol-soluble metabolites of common spruce bark for the development of new dermo-cosmetic agents. The active methanol extract was initially fractionated by Centrifugal Partition Chromatography (CPC) using a triphasic solvent system in a step-gradient elution mode. All resulting fractions were evaluated for their antibacterial activity, antioxidant activity and their capability to inhibit tyrosinase, elastase and collagenase activity. In parallel, the chemical composition of each fraction was established by combining a 13C-NMR dereplication approach and 2D-NMR analyses. As a result, fourteen secondary metabolites corresponding to stilbene, flavonoid and phenolic acid derivatives were directly identified in the CPC fractions. A high amount (0.93 g) of E-astringin was recovered from 3 g of crude extract in a single 125 min run. E-Astringin significantly induced the tyrosinase activity while E-piceid, taxifolin, and taxifolin-3′-O-glucopyranoside exhibited significant anti-tyrosinase activity. The above compounds showed important anti-collagenase and antimicrobial activities, thus providing new perspectives for potential applications as cosmetic ingredients. © 2016 by the authors; licensee MDPI

Bioactivity-guided identification of antimicrobial metabolites in Alnus glutinosa bark and optimization of oregonin purification by Centrifugal Partition Chromatography

Barks from conifers and broadleaved trees constitute abundant wastes generated from wood harvesting and logging activities. Extracts of such residues obtained from Alnus trees have been reported as interesting resources with potent antibacterial activities. The present study aims to determine the antimicrobial activity of a crude methanol extract prepared from the bark of Alnus glutinosa against a panel of 22 bacteria and yeasts and to optimize a purification method enabling the high production of the most active substances. Fractionation of the crude extract was performed by Centrifugal Partition Chromatography (CPC) using a three-phase solvent system composed of n-heptane, methyl-ter-butyl ether, acetonitrile and water. The major known compounds contained in the fractions produced by CPC were chemically profiled by 13C NMR dereplication, resulting in the unambiguous identification of oregonin, hirsutanonol, betulinic acid, and alusenone 1a. The antibacterial evaluation of the fractions by bioautography on Staphylococcus aureus revealed that oregonin, in addition to being the major metabolite of the crude extract (∼32% w/w), was the most active with an antibacterial inhibitory effect comparable to antibiotics. The purification of oregonin was optimized at the laboratory-scale by CPC. A single injection of 3.7 g of crude extract resulted in a recovery of 72% (850 mg) of the available oregonin at purity higher than 94%. © 2016 Elsevier B.V

In vitro dermo-cosmetic evaluation of bark extracts from common temperate trees

Wood residues produced from forestry activities represent an interesting source of biologically active, high value-Added secondary metabolites. In this study, 30 extracts from 10 barks of deciduous and coniferous tree species were investigated for their potential dermo-cosmetic use. The extracts were obtained from Fagus sylvatica, Quercus robur, Alnus glutinosa, Prunus avium, Acer pseudoplatanus, Fraxinus excelsior, Populus robusta, Larix decidua, Picea abies, and Populus tremula after three successive solid/liquid extractions of the barks with n-heptane, methanol, and methanol/ water. All extractswere evaluated for their radical scavenging capacity, for their elastase, collagenase, and tyrosinase inhibitory activities, as well as for their antibacterial activity against grampositive Staphylococcus aureus. In parallel, the global metabolite profiles of all extracts were established by 1D and 2D NMR and related to their biological activity. The results showed that the methanol extracts of Q. robur, A. glutinosa, L. decidua, and P. abies barks exhibit particularly high activities on most bioassays, suggesting their promising use as active ingredients in the dermocosmetic industry

The acute inflammatory response to copper(II)-doped biphasic calcium phosphates

International audienceInfection and inflammation are two key features to consider to avoid septic or aseptic loosening of bone-implanted biomaterials. In this context, various approaches to fine-tune the biomaterial's properties have been studied in order to modulate the crosstalk between immune and skeletal cells. Cation-doping strategies for tuning of calcium phosphates properties has been evidenced as a promising way to control the biomaterial-induced inflammatory process, and thus improving their osteoimmunomodulatory properties. Copper(II) ions are recognized for their antibacterial potential, but the literature on their impact on particulate material-induced acute inflammation is scarce. We synthesized copper(II) ions-doped biphasic calcium phosphate (BCP), intended to exhibit osteoimmunomodulatory properties. We addressed in vitro, for the first time, the inflammatory response of human primary polymorphonuclear neutrophils (PMNs) to copper(II) ions-doped or undoped (BCP) powders, synthesized by an original and robust wet method, in the presence or absence of LPS as a costimulant to mimic an infectious environment. ELISA and zymography allowed us to evidence, in vitro, a specific increase in IL-8 and GRO-α secretion but not MIP-1β, TNF-α, or MMP-9, by PMNs. To assess in vivo relevance of these findings, we used a mouse air pouch model. Thanks to flow cytometry analysis, we highlighted an increased PMN recruitment with the copper(II) ions-doped samples compared to undoped samples. The immunomodulatory effect of copper(II) ions-doped BCP powders and the consequent induced moderate level of inflammation may promote bacterial clearance by PMNs in addition to the antimicrobial potential of the material. Copper(II) doping provides new insights into calcium phosphate (CaP)-based biomaterials for prosthesis coating or bone reconstruction by effectively modulating the inflammatory environment

S6K1 controls pancreatic β cell size independently of intrauterine growth restriction.

Type 2 diabetes mellitus (T2DM) is a worldwide heath problem that is characterized by insulin resistance and the eventual loss of β cell function. As recent studies have shown that loss of ribosomal protein (RP) S6 kinase 1 (S6K1) increases systemic insulin sensitivity, S6K1 inhibitors are being pursued as potential agents for improving insulin resistance. Here we found that S6K1 deficiency in mice also leads to decreased β cell growth, intrauterine growth restriction (IUGR), and impaired placental development. IUGR is a common complication of human pregnancy that limits the supply of oxygen and nutrients to the developing fetus, leading to diminished embryonic β cell growth and the onset of T2DM later in life. However, restoration of placental development and the rescue of IUGR by tetraploid embryo complementation did not restore β cell size or insulin levels in S6K1-/- embryos, suggesting that loss of S6K1 leads to an intrinsic β cell lesion. Consistent with this hypothesis, reexpression of S6K1 in β cells of S6K1-/- mice restored embryonic β cell size, insulin levels, glucose tolerance, and RPS6 phosphorylation, without rescuing IUGR. Together, these data suggest that a nutrient-mediated reduction in intrinsic β cell S6K1 signaling, rather than IUGR, during fetal development may underlie reduced β cell growth and eventual development of T2DM later in life