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Deux tendances se dégagent actuellement dans les matériaux de restauration d’usage en médecine bucco-dentaire : celle de la simplification des procédures mais également de la création de matériaux « intelligents », capables d’induire un relargage ionique au long cours ou dans certaines conditions spécifiques. Afin de pallier la complexité de mise en œuvre et aux limites des composites, notre « gold standard » actuellement en technique directe, et de mieux exploiter le potentiel des ciments verre ionomères, les industriels ont tenté à plusieurs reprises de proposer des matériaux hybrides entre ces deux familles. Récemment, des alternatives aux ciments verres ionomères, avec des propriétés auto-adhésives, la présence de composante résineuse, et une libération ionique de fluor, ont été développées. Il nous a paru intéressant de faire une étude dans le but de caractériser leurs propriétés mécaniques, leur adhérence, et l’interface avec la dentine, de trois de ces nouveaux matériaux, en comparaison avec un ciment verre ionomère de haute viscosité. Ce document vise également à mieux connaitre la chimie et les particularités des matériaux à relargage ionique « historiques », pour ensuite comprendre la chimie des nouveaux matériaux arrivant sur le marché et les classifier.

BACKGROUND: Reference values of hemodynamic parameters for the assessment of prosthetic heart valves are necessary, and ideally need to be provided by entities independent of the valve manufacturers. Thus, the study aim was to provide, in vitro, normal reference values of the effective orifice area (EOA) for different models and sizes of mitral prosthetic valve, and to assess the determinants of EOA and mean transvalvular pressure gradient (mTPG). METHODS: Four models of mechanical prostheses were tested (one mono-leaflet, three bi-leaflet) and four models of bioprostheses (two bovine pericardial, two porcine) on a double-activation pulsed duplicator that was specifically designed and optimized for assessing the hemodynamic performance of mitral prosthetic valves. The hemodynamic conditions were standardized and included for bioprostheses: two mitral flow volumes, three mean aortic pressures, two heart rates, and three E/A ratios. The EOAs were measured with Doppler echocardiography, using the same method (continuity equation) as was used in the clinical setting. Overestimation in term of EOA was defined according to guidelines as >0.25 cm2. RESULTS: EOA reference values were recorded. For mono-leaflet prostheses (Medtronic Hall 7700, size 25 to 31 mm) 2.29 and 3.49; for bi-leaflet prostheses (St. Jude Medical Master and Master HP, sizes 25 to 33 mm and On-X valve, sizes 27-29 mm) 1.34 and 4.74 cm2; for porcine bioprostheses (Medtronic Mosaic CINCH, sizes 25 to 31 mm and St. Jude Epic 100, sizes 25 to 33 mm) 1.35 and 3.56 cm2; for bovine pericardial bioprosthetic valves (Edwards Perimount 6900P and Magna Ease 7300, sizes 25 to 33 mm) 1.67 and 2.36 cm2. There were some discrepancies between the normal reference EOAs measured compared to those provided by the prosthesis manufacturers, or in published reports. The bioprosthetic EOAs were shown to be smaller than the manufacturers' values in 32% of valves (by an average of 0.57 ± 0.28 cm2) versus in 7% of valves when compared to values reported elsewhere (by an average of 0.43 ± 0.17 cm2). The relationship between EOA and internal orifice area (IOA) varied according to the type of prosthesis. The EOA was close to the IOA in mechanical valves (regression slopes 0.87-0.99) but was much smaller than the IOA in bioprosthetic valves (slopes 0.25-0.30). The EOA was influenced by prosthesis diameter, prosthesis stent diameter and height, while the mTPG was influenced by EOA and heart rate. CONCLUSIONS: The present study has provided normal reference values of EOAs for several frequently used mitral prostheses. This information may be helpful for identifying and quantifying prosthetic valve dysfunction and prosthesis-patient mismatch.

International audience; INTRODUCTION: Ethanol lock (EL) is used to reduce catheter infections, but its impact on dialysis catheter dysfunction has not been studied. METHODS: We analyzed the rate of dialysis silicone catheter dysfunction after an interdialytic 60% EL in an open prospective controlled non crossover cohort study, with each patient being his or her own control. The study was divided into three consecutive 2-week periods: the pre- and post-intervention periods, in which interdialytic standard locks (SL) were used, and the intervention period, in which one EL was instilled during the first week, and two consecutively in the second week. We analyzed the rate of catheter dysfunction (exchange, use of fibrinolytic, reversing the lines, difficulty in instilling or withdrawing fluid) after EL or SL. RESULTS: In 30 patients, 90 EL were instilled. The rate of catheter dysfunction increased during the EL period (2 - 13%, p < 0.001), and between the two consecutive dialysis sessions before and after EL (p < 0.05). It decreased between the two consecutive dialysis sessions after EL and the following dialysis session after an SL (p < 0.05). No catheter was removed. The urea reduction ratio did not differ in dialysis after an SL and after an EL (0.77 vs. 0.73, p = 0.17). CONCLUSION: Short term EL is associated with a transient increase in catheter dysfunction, without resulting in catheter removal or decreasing dialysis efficiency.

Synthetic bone substitutes, such as calcium phosphate ceramics, give good results in clinical applications. In order to adapt to surgical sites, bioceramics come in the form of blocks or granules, and are either dense or porous. Combining these bioceramics with fibrin glue provides a mouldable and self-hardening composite biomaterial with the biochemical properties of each component. Critical-sized defects in the femoral condyle of rabbits were filled with TricOs/fibrin glue/bone marrow hybrid/composite material. The TricOs granules (1–2 mm) were composed of hydroxyapatite and beta tricalcium phosphate (60/40 in weight). The fibrin glue was composed of fibrinogen, thrombin and other biological factors and mixed with MBCP granules either simultaneously or sequentially. Bone marrow was also added to the MBCP/fibrin composite prior to filling the defects. After 3, 6, 12, and 24 weeks of implantation, the newly-formed bone was analysed with histology, histomorphometry and mechanical tests. The newly-formed bone had grown centripetally. Simultaneous application of fibrin glue showed better results for mechanical properties than sequential application after 6 weeks. Around 40% of bone had formed after 24 weeks in the three groups. Although the addition of bone marrow did not improve bone formation, the MBCP/fibrin material could be used in clinical bone filling applications. © 2006 Wiley Periodicals, Inc. J Biomed Mater Res, 2007

A new way of optimizing osteoconduction of biomaterials is to bring to them biological properties. In this work, we associated a novel release system with an electrodeposited calcium phosphate (CaP) coated titanium alloy Ti6Al4V. The characterization of this material was performed by means of light microscopy, scanning electron microscopy (SEM), scanning transmission electron microscopy (STEM) and X-ray energy dispersive spectroscopy (EDXS). The electrodeposited CaP coating was a tricalcium phosphate, and the release system was composed of microcapsules entrapped in an alginate film. We observed that the alginate matrix had a close contact with the coating. An intermediate layer containing calcium and phosphorus appeared at the interface between the alginate matrix and the CaP coating. These results allowed us to conclude that the association of two techniques, i.e. electrodeposition followed by deposition of a calcium alginate matrix, led to the elaboration of a new biomaterial.

Bioactive glasses are characterized by a bond to bone with a hydroxyl carbonate apatite layer. They enhance bone tissue formation and for this purpose are used in orthopedic surgery and in dental implantology. In the current work, we studied the biological response of human osteoblasts with a bioactive glass. This bioactive glass is based on 50% Si02, 20% Na2O, 16% CaO, 6% P2O5, 5% K20, 2% Al2O3 and 1% MgO and designated A9. Cracks and irregularities were observed on the material surface when it was immersed in the culture medium. In addition, energy dispersive X-ray analyses highlighted a selective release of the elements at the surface of the bioactive glass, such as Na+ and K+ ions, released from the first day, contrary to the Si, Al, Ca, P, and Mg elements, which were released more slowly. Cell proliferation kinetics, total protein synthesis, and DNA content of the osteoblasts in contact with bioactive glass were similar to control cells. The morphological studies by light and scanning electron microscopy revealed an increasing cellular density in culture with bioactive glass without contact inhibition. The immunohistochemical studies highlighted the expression of types I, III, and V collagens by osteoblasts cultured in the presence of bioactive glass. The pH measurement of the culture medium in the presence of bioactive glass demonstrated a slight alkalinization. We thus conclude that human osteoblasts preserve their properties in the presence of bioactive glass (A9). © 2003 Wiley Periodicals, Inc. J Biomed Mater Res 67A: 1205–1218, 2003

A new biomaterial is presented which consists of a cellulose derivative - silanised hydroxyethylcellulose (HEC-SIL) and biphasic calcium phosphate (BCP). Rheological properties of the polymer itself and its mixture with BCP are pH dependent. At pH = 10–12 HEC-SIL is liquid and undergoes quick gellation at pH < 9. Similarly the paste of HEC-SIL and BCP is fluid and injectable at higher pH and solidifies in biological solutions. The rate of this solidification can be easily controlled by the degree of substitution of hydroxyethylcellulose with silicoalkoxy groups.

International audience; A cationic amphiphilic peptide made of 10 leucine and 10 lysine residues, and four of its fluorescent derivatives in which leucines were substituted by Trp residues at different locations on the primary sequence have been synthesized. The interactions of these five peptides with neutral anionic or cationic vesicles were investigated using circular dichroism, steady state and time-resolved fluorescence with a combination of Trp quenching by brominated lipid probes, monolayers, modeling with minimization and simulated annealing procedures. We show that all the five peptides interact with neutral and anionic DMPC, DMPG, DOPC or egg yolk PC vesicles. The binding takes place whatever the peptide conformation in solution is. In the case of DMPC bilayers the binding free energy DeltaG is estimated at -8 kcal mole-1 and the number of phospholipid molecules involved is about 20-25 per peptide molecule. Peptides are bound as single-stranded alpha helices orientated parallel to the bilayer surface. In the anchoring of phospholipid head groups around the peptides, the lipid molecules are not smeared out in a plane parallel to the membrane surface but are organized around the hydrophilic face of the alpha helices like 'wheat grains around an ear' and protrude outside the bilayer towards the solvent. We suggest that such a lipid arrangement generates transient structural defects responsible for the membrane permeability enhancement. When an electrical potential is applied, the axis of the peptide helices remains parallel to the membrane surface and does not reorient to give rise to a bundle of helix monomers that forms transmembrane channels via a 'barrel stave' mechanism. The penetration depth of alpha helices in relation to the position of phosphorus atoms in the unperturbed lipid leaflet is estimated at 3.2 A.

The purpose of this study was to develop an injectable bone substitute (IBS) for percutaneous orthopedic surgery. The multiphasic material used was composed of a 2% aqueous solution of methylhydroxypropylcellulose (MHPC) and biphasic calcium phosphate (BCP, 60% hydroxyapatite and 40% beta-tricalcium phosphate) in which MHPC served as the carrier for 80-200 microm of BCP granules. The best BCP/polymer ratio was determined by the rheological properties and higher BCP content of the material. Steam sterilization was more effective than gamma irradiation in maintaining the stability of the mixture and conserving its physiochemical and mechanical properties. The in vitro biocompatibility of the composite was checked by direct-contact cytotoxicity and cell-proliferation assays. A preliminary in vivo test was performed in the rabbit using intraosseous implantations in the femoral epiphysis. Histological analysis was done after 1, 2, 4, and 10 weeks. Bone ingrowth into the IBS, in close association with BCP granules, was observed after 1 week and increased regularly from the surface inward at 2, 4, and 10 weeks. At the same time, smaller BCP granules (less than 80 microns in diameter) were degraded and resorbed. This injectable biomaterial proved suitable for cavity filling. The water solubility and viscosity of the polymer allow cells to recolonize, with in situ bonding of the mineral phase.

International audience; BACKGROUND: Volume targeted pressure support ventilation (VT-PSV) is a hybrid mode increasingly used to maintain a minimal tidal volume (VT) by automatically adjusting the level of inspiratory pressure. The objective of the study was to determine the ability of home ventilators to maintain the preset minimal VT during unintentional leaks in a VT-PSV mode. METHODS: Seven ventilators were tested on a lung bench with different circuit configurations and with different levels of unintentional leaks. Unintentional leaks were generated using calibrated holes. RESULTS: All the studied ventilators with a single-limb circuit with intentional leak (n = 5) were able to maintain the minimal preset VT during unintentional leaks. One ventilator overcompensated VT during unintentional leaks of high intensity. In contrast, all studied ventilators with a single circuit with an expiratory valve (n = 2) or a double-circuit (n = 3) but one failed to maintain the minimal VT during unintentional leaks. Unintentional leaks generated a decrease in inspiratory pressure, which was responsible for the fall in VT. CONCLUSIONS: Most of the studied ventilators with a single-limb circuit with intentional leak correctly estimate the expiratory VT and therefore successfully maintain the preset minimal VT during unintentional leaks, in contrast to most of the studied ventilators with a double-circuit, which paradoxically are not able to directly measure expiratory VT. Importantly, the VT-PSV mode, when used with most ventilators with expiratory valve or double-circuit, can paradoxically exacerbate the VT drop during unintentional leaks.

International audience; We report a general and simple approach to take control of the color of light-emitting two-luminophore hybrid nanowires (NWs). Our strategy is based on the spatial control at the nanoscale (coaxial geometry) and the spectral selection of the two kinds of luminophores in order to restrict complex charge and energy transfers. Thus, it is possible to control the color of the photoluminescence (PL) as an interpolation of the CIE (Commission Internationale de l'Eclairage) coordinates of each luminophore. For this purpose, we selected a green-emitting semiconducting polymer and a red-emitting hexanuclear metal cluster compound, (n-Bu4N)2Mo6Br8F6, dispersed in a poly(methyl-methacrylate) (PMMA) matrix. The great potential and the versatility of this strategy have been demonstrated for two configurations. First, a yellow PL with a continuous change along the nanowire has been evidenced when the proportion of the PPV shell versus the nanocomposite core, that is, the green/red volumic ratio, progressively shifts from 1:2 to 1:5. Second, an extremely abrupt change in the PL color with red-green-yellow segments has been achieved. A simple model corroborates the effectiveness of this strategy. PL excitation and time-resolved experiments also confirm that no significant charge and energy transfers are involved. The two-luminophore hybrid nanowires may find widespread nanophotonic applications in multicolor emitting sources, lasers and chemical and biological sensors.

International audience; BACKGROUND: Volume targeted pressure support ventilation (VT-PSV) is a hybrid mode increasingly used to maintain a minimal tidal volume (VT) by automatically adjusting the level of inspiratory pressure. The objective of the study was to determine the ability of home ventilators to maintain the preset minimal VT during unintentional leaks in a VT-PSV mode. METHODS: Seven ventilators were tested on a lung bench with different circuit configurations and with different levels of unintentional leaks. Unintentional leaks were generated using calibrated holes. RESULTS: All the studied ventilators with a single-limb circuit with intentional leak (n = 5) were able to maintain the minimal preset VT during unintentional leaks. One ventilator overcompensated VT during unintentional leaks of high intensity. In contrast, all studied ventilators with a single circuit with an expiratory valve (n = 2) or a double-circuit (n = 3) but one failed to maintain the minimal VT during unintentional leaks. Unintentional leaks generated a decrease in inspiratory pressure, which was responsible for the fall in VT. CONCLUSIONS: Most of the studied ventilators with a single-limb circuit with intentional leak correctly estimate the expiratory VT and therefore successfully maintain the preset minimal VT during unintentional leaks, in contrast to most of the studied ventilators with a double-circuit, which paradoxically are not able to directly measure expiratory VT. Importantly, the VT-PSV mode, when used with most ventilators with expiratory valve or double-circuit, can paradoxically exacerbate the VT drop during unintentional leaks.

International audience; BACKGROUND/AIMS: Different models of reconstructed skin are available, either to provide skin wound healing when this process is deficient, or to be used as an in vitro model. Nevertheless, few studies have focused on the mechanical properties of skin equivalent. Indeed, human skin is naturally under tension. Taking into account these features, the purpose of this work was to obtain a cellularized dermal equivalent (CDE), composed of collagen and dermal fibroblasts. METHODS: To counteract the natural retraction of CDE and to maintain it under tension, different biomaterials were tested. Selection criteria were biocompatibility, bioadhesion properties, ability to induce differentiation of fibroblasts into myofibroblasts and mechanical characterization, considering that of skin in vivo. These assays led to the selection of honeycomb of polyester. CDE constructed on this biomaterial was further characterized mechanically using tensile tests. RESULTS: The results showed that mechanical features of the obtained dermal equivalent, including myofibroblasts, were similar to skin in vivo. CONCLUSION: The original model of dermal equivalent presented herein may be a useful tool for clinical use and as an in vitro model for toxicological/pharmacological research.

In this experimental study, the nonspherical and translational behavior of individual coated microbubbles of different sizes, in contact with a 20-mu m thickness cellulose wall, are observed and categorized systematically. Images from two orthogonally positioned microscopes are merged and then recorded with an ultra-fast framing camera. Large nonspherical deformations were found with 2.25 MHz frequency ultrasound pulses having driving pressures from 80 to 325 kPa. A parametric model combining potential flow theory with a viscous boundary layer at the wall is developed and used to calculate stresses from the optically recorded microbubble oscillations. Peak shear stress of up to 300 kPa and normal stresses of up to 1 MPa are estimated when microbubbles are insonifed with a 2.25 MHz pulse at 325 kPa. The clinical relevance of these results is discussed. (E-mail: n.dejong@erasmusmc.nl) (C) 2011 World Federation for Ultrasound in Medicine & Biology.

International audience; Planar patch-clamp is a two-dimensional variation of traditional patch-clamp. By contrast to classical glass micropipette, the seal quality of silicon patch-clamp chips (i.e. seal resistance and seal success rate) have remained poor due to the planar geometry and the nature of the substrate and thus partially obliterate the advantages related to planar patch-clamp. The characterization of physical parameters involved in seal formation is thus of major interest. In this paper, we demonstrate that the physical characterization of surfaces by a set of techniques (Atomic Force Microscopy (AFM), Scanning Electron Microscopy (SEM), X-ray Photoelectron Spectroscopy (XPS), surface energy (polar and dispersive contributions), drop angles, impedance spectroscopy, combined with a statistical design of experiments (DOE)) allowed us discriminating chips that provide relevant performances for planar patch-clamp analysis. Analyses of seal quality demonstrate that dispersive interactions and micropore size are the most crucial physical parameters of chip surfaces, by contrast to surface roughness and dielectric membrane thickness. This multi-scale study combined with electrophysiological validation of chips on a diverse set of cell-types expressing various ion channels (IRK1, hERG and hNa(v)1.5 channels) unveiled a suitable patch-clamp chip candidate. This original approach may inspire novel strategies for selecting appropriate surface parameters dedicated to biochips.

International audience; Surface-initiated atom transfer radical polymerization (ATRP) has been used to prepare antifouling copolymer brushes based on 2-(2-methoxyethoxy)ethyl methacrylate (MEO(2)MA) and hydroxyl-terminated oligo(ethylene glycol) methacrylate (HOEGMA). The amount of hydroxyl reactive groups incorporated into the brushes was varied by changing the composition of the monomer mixture. These coatings were subsequently functionalized by a natural antibacterial peptide, magainin I, via an oriented chemical grafting on hydroxyl groups, which maintains the activity of the peptide. The antibacterial activity of the functionalized brushes was successfully tested against two different strains of gram-positive bacteria.

International audience; The present paper investigates the rheological properties of silated hydroxypropylmethylcellulose (Si-HPMC) biohydrogel used for biomaterials and tissue engineering applications. The general property of this modified cellulose ether is the occurrence of self-hardening due to silanol condensation subsequent to a decrease in pH (from 12.4 to nearly 7.4). The behavior of unsterilized and sterilized Si-HPMC solutions in diluted and concentrated domains is first described and compared. In addition, the influence of physiological parameters such as pH and temperature on the rate of the gelation process is studied. In dilute solution, the intrinsic viscosity ([eta]) of different pre-steam sterilization Si-HPMC solutions indicates that macromolecular chains occupy a larger hydrodynamic volume than the post-steam sterilization Si-HPMC solutions. Although the unsterilized Si-HPMC solutions demonstrate no detectable influence of pH upon the rheological behavior, a decrease in the limiting viscosities (eta(0)) of solutions with increasing pH is observed following steam sterilization. This effect can be explained by the formation of intra- and intermolecular associations during the sterilization stage originating from the temperature-induced phase separation. The formation of Si-HPMC hydrogels from injectable aqueous solution is studied after neutralization by different acid buffers leading to various final pHs. Gelation time (t(gel)) decreases when pH increases (t(gel) varies from 872 to 11s at pH 7.4 and 11.8, respectively). The same effect is observed by increasing the temperature from 20 to 45 degrees C. This is a consequence of the synergistic effect of the increased reaction rate and acid buffer diffusion. pH and temperature are important parameters in the gelation process and their influence is a key factor in controlling gelation time. By adapting the gel parameters one could propose hydrogels with cross-linking properties adapted to clinical applications by controlling the amount of pH of neutralization and temperature.

Background— Long-term patency of conventional synthetic grafts is unsatisfactory below a 6-mm internal diameter. Poly(ε-caprolactone) (PCL) is a promising biodegradable polymer with a longer degradation time. We aimed to evaluate in vivo healing and degradation characteristics of small-diameter vascular grafts made of PCL nanofibers compared with expanded polytetrafluoroethylene (ePTFE) grafts. Methods and Results— We prepared 2-mm–internal diameter grafts by electrospinning using PCL (M n =80 000 g/mol). Either PCL (n=15) or ePTFE (n=15) grafts were implanted into 30 rats. Rats were followed up for 24 weeks. At the conclusion of the follow-up period, patency and structural integrity were evaluated by digital subtraction angiography. The abdominal aorta, including the graft, was harvested and investigated under light microscopy. Endothelial coverage, neointima formation, and transmural cellular ingrowth were measured by computed histomorphometry. All animals survived until the end of follow-up, and all grafts were patent in both groups. Digital subtraction angiography revealed no stenosis in the PCL group but stenotic lesions in 1 graft at 18 weeks (40%) and in another graft at 24 weeks (50%) in the ePTFE group. None of the grafts showed aneurysmal dilatation. Endothelial coverage was significantly better in the PCL group. Neointimal formation was comparable between the 2 groups. Macrophage and fibroblast ingrowth with extracellular matrix formation and neoangiogenesis were better in the PCL group. After 12 weeks, foci of chondroid metaplasia located in the neointima of PCL grafts were observed in all samples. Conclusions— Small-diameter PCL grafts represent a promising alternative for the future because of their better healing characteristics compared with ePTFE grafts. Faster endothelialization and extracellular matrix formation, accompanied by degradation of graft fibers, seem to be the major advantages. Further evaluation of degradation and graft healing characteristics may potentially lead to the clinical use of such grafts for revascularization procedures.

Polymer grafting of polystyrene (PS) on nitrogen-doped multiwall carbon nanotubes (CNx) was successfully obtained by a "grafting from" technique. The production method involves the immobilization of initiators, using wet chemistry, onto the nanotube surface, followed by an in situ surface-initiated polymerization. The polymer-grafting carbon nanotubes synthesis includes the free radical functionalization of CNx and the "controlled/living" Nitroxide Mediated Radical Polymerization (NMRP). The obtained products were studied using several microscopic techniques as scanning electron microscopy (SEM), high-resolution transmission electron microscopy (HRTEM), and electron energy loss spectroscopy (EELS). The characterization also includes thermogravimetric analysis (TGA), Raman spectroscopy, infrared spectroscopy, and electron spin resonance (ESR), among others. The analyzed samples were also compared with solutions fabricated by physical blending of the polymer and CNx nanotubes. These results indicate that the nanotube radical functionalization, the chemical grafting, and the polymerization reaction were obtained over CNx when NMRP method was successfully used, giving rise to a uniform PS layer of several nanometers grafted on the outer surface of the CNx nanotubes. Several properties of the PS-grafted CNx nanotubes were also studied. It is shown that the production method leads to a narrower distribution of the external diameters. Moreover, their solubilization in organic solvents is greatly improved. Finally, the dispersion of PS-grafted CNx into a PS matrix is studied to determine the differences in filler dispersion and interfacial adhesion strength, in comparison with nanocomposites elaborated with as-produced CNx.

International audience; To study cell attachment to biomaterials, several proteins such as fibronectin, collagen IV, heparin, immunoglobulin G, and albumin have been deposited onto polystyrene adsorbed on a self-assembled monolayer (silane or thiol) on glass or gold, respectively. The different steps of this multilayer assembly have been characterized by electrochemical impedance spectroscopy (EIS). These data are compared to those of adhesion rate, viability percentage, and cytoskeleton labeling for a better understanding of the cell adhesion process to each protein. All the proteins are endothelial cell adhering biomolecules but not with the same features. A linear relationship has been established between adhesion rate and resistance of the endothelial cell/protein interface for all negatively charged proteins.

Several studies have shown that macro micro porous bioceramics ectopically implanted promote bone tissue formation. This study aims at investigating the inflammatory response towards biphasic calcium phosphate (BCP) ceramic micro particles. BCP composed of hydroxyapatite (HA) and beta-tricalcium phosphate, HA/beta -TCP ratio of 50/50, were prepared by sintering at 1200 degrees C for 5 h. After crushing, 3 fractions of BCP micro particles < 20, 40-80 and 80-200 micro m were sieved. The micro particles were carefully characterized by using X-ray diffraction (XRD), scanning electron microscopy (SEM) and laser scattering. The inflammatory reactions induced by BCP micro particles implanted in quadriceps muscles of rats for 7, 14 and 21 days were studied by histology (n = 8/group). A fibrous tissue encapsulation of the BCP micro particles implanted in muscle tissue was observed and fibrosis was similar for the 3 groups of micro particles. The comparison of the cellular response indicated that the total number of cells was significantly higher for BCP < 20 micro m than for 40-80 and 80-200 micro m (p < 0.0001). The number of macrophages was relatively higher for the smallest than for the intermediate and largest fractions (p < 0.0001). The relative percentage of giant cells was higher for the intermediate and largest size of particles than for the smallest. The number of lymphocytes was comparable for the 3 fractions and after the 3 delays. Therefore, the BCP micro particles < 20 micro m initiated an inflammatory response which might play an important role in osteogenesis.

Calcium phosphate cements (CPCs) are successfully used as bone substitutes in dentistry and orthopaedic applications. This study investigated the physico-chemical-mechanical properties of and in vitro biological properties (cell response) of CPCs prepared with amorphous calcium carbonate phosphate (ACCP) doped with magnesium (ACCP-Mg), zinc (ACCp-Zn) or fluoride (ACCP-F) ions. The experimental CPC consisted of alpha-TCP, doped ACCP, and MPCM powders as matrix and biphasic calcium phosphate (BCP) granules. X-ray diffraction analysis showed that the matrix converted to apatite with poor crystallinity (reflecting small crystal size) after setting for 24 h, while BCP remained apparently unchanged. Cements with ACCP-F (F-CPC) had shorter setting times and greater compressive strength compared to cements with ACCP-Mg (Mg-CPC) or ACCP-Zn (Zn-CPC). Scanning electron microscopy (SEM) showed that crystals set on Mg-CPC and Zn-CPC were smaller compared to those on F-CPC. The total porosity of Mg-CPC was greater compared to Zn-CPC or F-CPC. Osteoblast-like cells, MC3T3-E1, remained viable and maintained their ability to express alkaline phosphatase in contact with the CPCs with doped ACCPs.

Calcium phosphates coatings were deposited onto titanium alloy discs via en electrodeposition method. Titanium alloy discs were blasted with calcium phosphate particles, then etched in a mixture of nitric and fluoric acids and rinsed in demineralized water. The titanium alloy disc (cathode) and platinum mesh (anode) were immersed in a supersaturated calcium phosphate electrolyte buffered at pH 7.4 and connected to a current generator. The microstructure, chemical composition and crystallinity of the electrodeposited coatings were studied as function of time 10-120 min, temperature 25-80 degrees C, current density 8-120 mA/cm(2), magnesium and hydrogen carbonate amounts (0.1-1 mM). Uniform calcium phosphate coatings were obtained in 30 min but coating thickness increased with deposition time. Raising the temperature of electrolyte resulted in more uniform coatings as ionic mobility increased. Low current density was preferable due to hydrogen gas evolving at the cathode, which disturbed the deposition of calcium phosphate crystals on titanium. The amounts of magnesium and hydrogen carbonate ions affected both the homogeneity and morphology of the coatings. This study showed that the electrodeposition method is efficient for coating titanium with osteoconductive calcium phosphate layers.

OBJECTIVES: The purpose of this study was to develop an animal model of prosthetic infection and compare in vivo bacterial infectiosity of different biomaterials used in vaginal surgery. MATERIALS AND METHODS: We implanted 36 prostheses of poly(lactic acid) with 94% L forms (PLA94), in a model of incisional abdominal hernia in Wistar rats. Bacterial inoculation was done just after implantation with three strains of Escherichia coli of variable virulence, two different concentrations and two different times of inoculation (during surgery or 48 hours after). All meshes were explanted and animals sacrificed on day 30 after intervention. Bacteriology and histology were then performed. In the same way, three materials used in vaginal surgery (knitted light-weight polypropylene [PP], thermoformed PP [Uratape] and polyurethane coated poly[ethylene terephtalate] [PTFE]) were tested and compared to the PLA94 using the same protocol. RESULTS: All inoculated prostheses were still infected at day 30 after implantation with the same E. coli strain. There was a significant difference in bacterial infectiosity linked to virulence of the inoculated strain (p=.005) and the amount injected (P

International audience; A surface coating based on polylysine/hyaluronic acid multilayers was designed and acted as a reservoir for an antiproliferative agent, paclitaxel (Taxol). Absolutely no chemical modification of polyelectrolytes or of the drug was needed and the final architecture was obtained in an extremely simple way using the layer-by-layer method. The paclitaxel dose available for human colonic adenocarcinoma cells HT29 seeded on the films could be finely tuned. Moreover, the accessibility of the drugs was controlled by adding on the top of the drug reservoir a capping made of synthetic polyelectrolyte multilayers. This capping was also required to allow adhesion of HT29 cells. Paclitaxel activity was maintained after embedding in the polyelectrolyte multilayers and cellular viability could be reduced by about 80% 96 h after seeding. The strategy described in this paper could be valuable for various other drug/cell systems.

International audience; In this study, microspheres designed for embolization, defined as GF2000-Trisacryl MS (GF-MS) and DEAE-Trisacryl MS (DEAE-MS), were originally PEGylated using (3-amino propyl) triethoxy silane as coupling agent. Indomethacin was loaded into both PEGylated and non-PEGylated DEAE-MS, displaying ion-exchange ability, through a batch process with a respective capacity of 1.2 and 0.25 g/g. The morphology of naked and PEGylated MS was evaluated by scanning electron microscopy (SEM). Both micosphere resins surface looked like orange skin, although DEAE-MS showed a slightly rougher surface due to the copolymerization process. PEGylated microspheres have a most likely swelling surface owing to the presence of PEG hydrophilic chains. The mean diameters were of about 66 and 60 microm for GF-MS and DEAE-MS, respectively. Data obtained for PEGylated MS by Fourier Transform Infrared spectroscopy (FTIR) confirmed that microspheres were successfully PEGylated. Finally, complement activation in vitro was performed to evaluate the activating capacity of different microspheres. Both PEGylated GF-MS and DEAE-MS activated the complement system of about 33% less than their corresponding naked microspheres, while loading PEGylated DEAE-MS with indomethacin almost suppressed complement activation. This inhibiting role implies that PEGylation as well as loading the microspheres with anti-inflammatory drug has a compact effect on the interaction of microspheres with blood proteins.

récupéré dans HAL-INSERM; Short-term physico-chemical reactions at the interface between bioactive glass particles and biological fluids are studied for three glasses with different bioactive properties; these glasses are in the SiO(2)-Na(2)O-CaO-P(2)O(5)-K(2)O-Al(2)O(3)-MgO system. Our aim is to show the difference between the mechanisms of their surface reactions. The relation between the composition and the bioactive properties of these glasses is also discussed. The elemental analysis is performed at the submicrometer scale by scanning transmission electron microscopy associated with energy-dispersive X-ray spectroscopy and electron energy loss spectroscopy. After different immersion times (ranging from 0 to 96 h) of bioactive glass particles in a simulated biological solution, results show the formation of different surface layers at the glass periphery in the case of two bioactive glasses (A9 and BVA). For the third glass (BVH) we do not observe any surface layer formation or any modification of the glass composition. For the two other glasses (A9 and BVA), we observe the presence of different layers: an already observed (Si, O, Al) rich layer at the periphery, a previously demonstrated thin (Si, O) layer formed on top of the (Si, O, Al) layer and a (Ca, P) layer. We determine the different steps of the mechanisms of the surface reactions, which appear to be similar in these glasses, and compare the physico-chemical reactions and kinetics using the different immersion times. The A9 glass permits the observation of all important steps of the surface reactions which lead to bioactivity. This study shows the important relationship between composition and bioactivity which can determine the medical applicability of the glass.

International audience; Calcium phosphate ceramics are currently used as bone graft substitutes in various types of clinical applications. Fibrin glue is also used in surgery due to its haemostatic, chemotactic and mitogenic properties. By combining these two biomaterials, new composite scaffolds were prepared. In this study, we attempt to analyse whether thrombin concentration in the fibrin glue could influence the properties of the composite. The association between fibrin glue and calcium phosphate ceramic granules was characterized at the ultra structural level. Micro and macroporous biphasic calcium phosphate ceramic granules with a diameter of 1-2mm composed of hydroxyapatite and beta-tricalcium phosphate (60/40) were associated to fibrin glue. The composites were observed by scanning and transmission electron microscopy and microcomputed tomography. Fibre thickness, porosity and homogeneity of the fibrin clot were modified by increased the thrombin concentration. Mixing fibrin glue with calcium phosphate granules (1:2) did not modify the microstructure of the fibrin clot in the composite. Nevertheless, thrombin interacted with the bioceramic by inducing the nucleation of crystalline precipitate at the ceramic/fibrin glue interface. Combining fibrin sealant and calcium phosphate ceramics could lead to new scaffolds for bone tissue engineering with the synergy of the properties of the two biomaterials.

International audience; Raw nacre implants persist even after 9 months of implantation into bone tissue in sheep. However the nacre surface undergoes a limited biodegradation process. Smooth-surfaced nacre implants were seen to become microporous after implantation. The results of these long-term, in vivo studies show that the overall process involves bone-resorbing cells, relies on a two-phase mechanism and may correspond to a regulation process. The rate of surface change depends on the bone implantation site and the nacre/bone interaction. The in vivo biodegradability of nacre is a highly variable parameter. The size and shape of the implanted nacre and the cellular environment of the implant are key factors in determining the biodegradation kinetics of the nacre in a living system.

International audience; The influence of processing parameters and synthetic strategies in the properties of sol-gel derived silica matrices intended for the release of bioactive compounds was investigated. The time-evolution of the matrix properties during its aging at room temperature in the dry and wet forms was investigated by measuring some of its physical and drug retaining properties. The results indicate that long term gel aging in the wet form is fundamental for the obtainment of dry matrices that are stable upon storage, a fundamental requirement for any practical application. In the case of hybrid matrices obtained by replacing part of the tetraethoxysilane precursor with mono-methyl trimethoxysilane, the order of addition of the reaction component is also important in determining the properties of the final dry gel, probably by influencing the polymer structural properties. This parameter acts synergistically with the matrix composition in determining the release properties of xerogels embedded with bioactive compounds.

A possible complication associated with the implantation of hydroxyapatite (HA)-based prosthesis is the release of particles. Those particles can be phagocyted by monocytes that are among the first cells to colonize the inflammatory site. The activated monocytes produce inflammatory mediators, such as cytokines, which cause osteoclasts activation. It has previously been demonstrated using a surface area ratio (ratio of the total surface of the given particles to the surface area of cells) of 1 to 1 that there was a correlation between the expression and production of cytokines induced by HA. The present work studies the effect of physical characteristics of HA particles on the production of various inflammatory cytokines (tumour necrosis factor-alpha, interleukin (IL)-6, and IL-8) and anti-inflammatory cytokine (IL-10). However, the experiments were performed using a surface area ratio of 10 to 1. Our data demonstrate that all the particles, whatever their characteristics, induced a high expression of cytokines but the production was different, meaning that there was a post-transcriptional regulation. The size and sintering temperature seemed to be a characteristics that were less important compared to the shape; the needle particles appeared to induce the most important production of all the cytokines studied.

International audience; Synthesis of grafting silane on a hydro soluble cellulose ether (HPMC) was described. In alkaline medium, this derivate is under gel form. With a decrease of the pH, a self-hardening occurs due to the silanol condensation. For potential biomedical use, we described the silated-HPMC synthesis, the gel behavior after steam sterilization and the parameters of the silanol condensation i.e. pH, silane percentage and temperature. Minimum kinetic of the condensation was observed for pH between 5.5 and 6.5. So temperature catalyzed the reaction and the self-hardening speed was increased by silane percentage.

Hydroxyapatite used as bone replacement can lead to particle release in the implantation site. These particles interact with monocytes, which are the first immune cells to colonize the implant and an inflammatory site. Thanks to cryo-X-ray microanalysis, we can observe cells in a state close to the physiological one and we have access to diffusible ions. We paid particular attention to the potassium-to-sodium ratio, which is one of the best viability criteria. We used this method to study the interaction between three hydroxyapatite particles treated at three different temperatures (not treated, treated at 600 °C and 1180 °C), and monocytes. In the culture condition, the hydroxyapatite treated at 1180 °C underwent the least dissolution. We demonstrate that monocytes were altered by the three hydroxyapatite particles. The hydroxyapatite particules treated at 600 °C were found to be more toxic. © 2001 John Wiley & Sons, Inc. J Biomed Mater Res (Appl Biomater) 58: 238–246, 2001

Letter to the Editors; International audience; No abstract is available for this article