Impact of the chemical composition of poly-substituted hydroxyapatite particles on the in vitro pro-inflammatory response of macrophages

International audienceTo improve the biological properties of calcium phosphate (CaP) bone substitute, new chemical compositions are under development. In vivo such materials are subject to degradation that could lead to particles release and inflammatory reactions detrimental to the bone healing process. This study aimed at investigating the interactions between a murine macrophage cell line (RAW 264.7) and substituted hydroxyapatite particles presenting promising biological properties. Micron size particles of stoichiometric and substituted hydroxyapatites (CO 3 substitution for PO 4 and OH; SiO 4 substitution for PO 4; CO 3 and SiO 4 co-substitution) were obtained by aqueous precipitation followed by spray drying. Cells, incubated with four doses of particles ranging from 15 to 120 µg/mL, revealed no significant LDH release or ROS production, indicating no apparent cytotoxicity and no oxidative stress. TNF-α production was independent of the chemistry of the particles; however the particles elicited a significant dose-dependent pro-inflammatory response. As micron size particles of these hydroxyapatites could be at the origin of inflammation, attention must be paid to the degradation 2 behavior of substituted hydroxyapatite bone substitute in order to limit, in vivo, the generation of particulate debris

Accurate characterization of pure silicon-substituted hydroxyapatite powders synthesized by a new precipitation route

International audienceThis paper presents a new aqueous precipitation method to prepare silicon-substituted hydroxyapatites Ca10(PO4)6-y(SiO4)y(OH)2-y(VOH)2-y (SiHAs) and details the characterization of powders with varying Si content up to y = 1.25 mol molSiHA−1. X-ray diffraction, transmission electron microscopy, solid-state nuclear magnetic resonance and Fourier transform infrared spectroscopy were used to accurately characterize samples calcined at 400°C for 2 h and 1000°C for 15 h. This method allows the synthesis of monophasic SiHAs with controlled stoichiometry. The theoretical maximum limit of incorporation of Si into the hexagonal apatitic structure is y < 1.5. This limit depends on the OH content in the channel, which is a function of the Si content, temperature and atmosphere of calcination. These results, particularly those from infrared spectroscopy, raise serious reservations about the phase purity of previously prepared and biologically evaluated SiHA powders, pellets and scaffolds in the literature

Caractérisation de tissu osseux et de biomatériaux pour la régénération osseuse sur gros volume.

L’objectif de cette étude est de développer un processus expérimental de régénération de tissus osseux de grand volume. Une première étape vise à produire du matériau osseux à partir de lambeau de périoste vascularisé et à le caractériser grâce a des essais d’indentation. Ensuite, nous développons un process impliquant un biomatériau poreux et biodégradable utilisé comme réceptacle de cellules mésenchymateuses. Dans les deux cas, le nouveau matériau obtenu est étudié grâce à des tests mécaniques et biologiques

Development of multisubstituted hydroxyapatite nanopowders as biomedical materials for bone tissue engineering applications

Ionic substitutions have been proposed as a tool to control the functional behavior of synthetic hydroxyapatite (HA), particularly for Bone Tissue Engineering applications. The effect of simultaneous substitution of different levels of carbonate (CO3) and silicon (Si) ions in the HA lattice was investigated. Furthermore, human bone marrow‐derived mesenchymal stem cells (hMSCs) were cultured on multi‐substituted HA (SiCHA) to determine if biomimetic chemical compositions were osteoconductive. Of the four different compositions investigates, SiCHA‐1 (0.58 wt % Si) and SiCHA‐2 (0.45 wt % Si) showed missing bands for CO3 and Si using FTIR analysis, indicating competition for occupation of the phosphate site in the HA lattice; 500°C was considered the most favorable calcination temperature as: (i) the powders produced possessed a similar amount of CO3 (2–8 wt %) and Si (<1.0 wt %) as present in native bone; and (ii) there was a minimal loss of CO3 and Si from the HA structure to the surroundings during calcination. Higher Si content in SiCHA‐1 led to lower cell viability and at most hindered proliferation, but no toxicity effect occurred. While, lower Si content in SiCHA‐2 showed the highest ALP/DNA ratio after 21 days culture with hMSCs, indicating that the powder may stimulate osteogenic behavior to a greater extent than other powder

Pathema: a clade-specific bioinformatics resource center for pathogen research

Pathema (http://pathema.jcvi.org) is one of the eight Bioinformatics Resource Centers (BRCs) funded by the National Institute of Allergy and Infectious Disease (NIAID) designed to serve as a core resource for the bio-defense and infectious disease research community. Pathema strives to support basic research and accelerate scientific progress for understanding, detecting, diagnosing and treating an established set of six target NIAID Category A–C pathogens: Category A priority pathogens; Bacillus anthracis and Clostridium botulinum, and Category B priority pathogens; Burkholderia mallei, Burkholderia pseudomallei, Clostridium perfringens and Entamoeba histolytica. Each target pathogen is represented in one of four distinct clade-specific Pathema web resources and underlying databases developed to target the specific data and analysis needs of each scientific community. All publicly available complete genome projects of phylogenetically related organisms are also represented, providing a comprehensive collection of organisms for comparative analyses. Pathema facilitates the scientific exploration of genomic and related data through its integration with web-based analysis tools, customized to obtain, display, and compute results relevant to ongoing pathogen research. Pathema serves the bio-defense and infectious disease research community by disseminating data resulting from pathogen genome sequencing projects and providing access to the results of inter-genomic comparisons for these organisms

Ceramic devices for bone regeneration

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Fixation du cadmium par une hydroxyapatite phosphocalcique (étude cinétique et thermodynamique)

Les propriétés physico-chimiques des hydroxyapatites permettent d'envisager leur utilisation comme décontaminant des effluents liquides pollués par les métaux lourds, notamment le cadmium, mais également comme matrice de stockage de cet élément toxique. La mise en œuvre du procédé de stabilisation des cations Cd2+ dépend du mode de piégeage par l'apatite. Dans ce cadre, le mécanisme de fixation du cadmium par une hydroxyapatite phosphocalcique Ca10(PO4)6(OH)2 en solution aqueuse a été déterminé. L'immobilisation des cations Cd2+ a été réalisée en conditions statiques, sous forme de test en batch sur une hydroxyapatite phosphocalcique synthétisée au laboratoire. La quantité de cadmium immobilisé est proportionnelle à la surface spécifique des poudres, et peut atteindre 7,1 moles par mole d'apatite mise en jeu. La détermination du mécanisme s'est appuyée sur une analyse chimique des poudres et des filtrats issus des expériences de fixation. Quels que soient les paramètres expérimentaux, les isothermes obtenues après deux semaines de fixation ont une allure générale de type Langmuir. La principale réaction d'immobilisation du cadmium est composée de deux étapes successives. La première est un échange ionique rapide entre les cations Cd2+ de la solution et les cations Cd2+ adsorbés sur des sites spécifiques à la surface des grains d'apatite. La deuxième, plus lente, est la précipitation d'une hydroxyapatite calcocadmiée, initiée par les cations Cd2+ adsorbés qui deviennent des sites de germination. La croissance de cette couche épitaxiale s'effectue via une redistribution superficielle de la matière et/ou via un mûrissement d'Ostwald au sein de la suspension. Les cristaux de poudre chargée en cadmium sont ainsi composés d'un cœur en hydroxyapatite calcique pure Ca10(PO4)6(OH)2, entouré d'une couche d'hydroxyapatite calcocadmiée Ca10-xCdx(PO4)6(OH)2 (4<=x<=10). Parallèlement deux réactions minoritaires se produisent : la précipitation homogène d'une apatite calcocadmiée, suivie de la dissolution lente de l'hydroxyapatite calcique initiale. Selon la température, entre 17% et 35% de la quantité totale de cadmium fixé après deux semaines de contact sont adsorbés à la surface des grains. La précipitation de surface incorpore en solution solide apatitique entre 59% et 82% de cette même quantité, et la précipitation homogène de 1% à 6%.Use of synthetic apatites could be a way of eliminating cadmium from waste industrial aqueous solution and water. Apatites could be also used as host matrix for the storage of this toxic element. The implementation of this stabilization process depends on the nature of the interactions between the Cd2+ cations and the apatite crystals. Within this framework, the fixation mechanism of cadmium by a calcium phosphate hydroxyapatite Ca10(PO4)6(OH)2 in aqueous solution was determined. At first, the calcium phosphate hydroxyapatite was synthesized. Then, the Cd2+ immobilization was performed by "batch " experiments. The mechanism was determined from a chemical analysis of the loaded powders and the supernatant. The isothermal data obtained after two weeks are well fitted by the simple Langmuir adsorption isotherm whatever the experimental parameters may be. The amount of immobilized cadmium is proportional to the powders surface area, and can reach 7.1 mol per mol of apatite. The main immobilization reaction is made of two successive steps. The first one is a fast ionic exchange between Cd2+ cations of the bulk solution and Cd2+ cations adsorbed on specific sites at the apatite surface. The second, slower than the previous one, is the heterogeneous precipitation of a cadmium-containing hydroxyapatite. This reaction is initiated by the Cd2+ cations adsorbed on the surface of the particles. They become the germination sites of the calcium-cadmium hydroxyapatite crystals. The growth of this epitaxial layer is carried out via a local redistribution of the matter at the grains surface, and/or via an Ostwald ripening within the bulk solution. The loaded powder is made of a pure calcium hydroxyapatite Ca10(PO4)6(OH)2 core, surrounded by a shell of cadmium-containing hydroxyapatite Ca10-xCdx(PO4)6(OH)2 (4<=x<=10). In the same time two minor reactions occur, a homogeneous precipitation of a cadmium-containing hydroxyapatite followed by the slow dissolution of the initial calcium hydroxyapatite. According to the temperature, between 17% and 35% of the total amount of cadmium fixed after two weeks of contact are adsorbed on grains surface. The surface precipitation incorporates in an apatitic solid solution between 59% and 82% of this quantity, and the homogeneous precipitation from 1 % to 6%.LIMOGES-BU Sciences (870852109) / SudocSudocFranceF

Porous hydroxyapatite bioceramics produced by impregnation of 3D-printed wax mold: Slurry feature optimization

International audienceNowadays, new engineering developments that combine computational methods and additive manufacturing are able to overcome the current limitations of conventional ceramic manufacturing methods. In this context, a robust bioceramic manufacturing process based on the impregnation of three-dimensional (3D) printed wax molds was developed. The innovative and creative potential of this process is based on the ability to impregnate homogeneously a complex structural design in a reproducible way. We investigated on the optimization of hydroxyapatite slurry based on its preparation parameters. Scaffolds were successfully produced with a wide range of slurry formulations. The results indicate that the bioceramics quality is primarily determined by the slurry drying rate in contact with the mold for a suspension viscosity less than or equal to 80 mPa s. In addition, this process, which allows for phase preservation, can be easily adapted to a large variety of ceramic phases and a wide range of biological applications

Synthesis and Characterization of Cx-Siy-HA for Bone Tissue Engineering Application

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