2,686 research outputs found

    Calcium Phosphate as a Key Material for Socially Responsible Tissue Engineering

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    Socially responsible technologies are designed while taking into consideration the socioeconomic, geopolitical and environmental limitations of regions in which they will be implemented. In the medical context, this involves making therapeutic platforms more accessible and affordable to patients in poor regions of the world wherein a given disease is endemic. This often necessitates going against the reigning trend of making therapeutic nanoparticles ever more structurally complex and expensive. However, studies aimed at simplifying materials and formulations while maintaining the functionality and therapeutic response of their more complex counterparts seldom provoke a significant interest in the scientific community. In this review we demonstrate that such compositional simplifications are meaningful when it comes to the design of a solution for osteomyelitis, a disease that is in its natural, non-postoperative form particularly prevalent in the underdeveloped parts of the world wherein poverty, poor sanitary conditions, and chronically compromised defense lines of the immune system are the norm. We show that calcium phosphate nanoparticles, which are inexpensive to make, could be chemically designed to possess the same functionality as a hypothetic mixture additionally composed of: (a) a bone growth factor; (b) an antibiotic for prophylactic or anti-infective purposes; (c) a bisphosphonate as an antiresorptive compound; (d) a viral vector to enable the intracellular delivery of therapeutics; (e) a luminescent dye; (f) a radiographic component; (g) an imaging contrast agent; (h) a magnetic domain; and (i) polymers as viscous components enabling the injectability of the material and acting as carriers for the sustained release of a drug. In particular, calcium phosphates could: (a) produce tunable drug release profiles; (b) take the form of viscous and injectable, self-setting pastes; (c) be naturally osteo-inductive and inhibitory for osteoclastogenesis; (d) intracellularly deliver bioactive compounds; (e) accommodate an array of functional ions; (f) be processed into macroporous constructs for tissue engineering; and (g) be naturally antimicrobial. All in all, we see in calcium phosphates the presence of a protean nature whose therapeutic potentials have been barely tapped into

    Astromimetics: The Dawn of a New Era for (Bio)materials Science?

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    Composite, multifunctional fine particles are likely to be at the frontier of materials science in the foreseeable future. Here we present a submicron composite particle that mimics the stratified structure of the Earth by having a zero-valent iron core, a silicate/silicide mantle, and a thin carbonaceous crust resembling the biosphere and its biotic deposits. Particles were formulated in a stable colloidal form and made to interact with various types of healthy and cancer cells in vitro. A selective anticancer activity was observed, promising from the point of view of the intended use of the particles for tumor targeting across the blood–brain barrier. As an extension of the idea underlying the fabrication of a particle mimicking the planet Earth, we propose a new field of mimetics within materials science: astromimetics. The astromimetic approach in the context of materials science consists of the design of particles after the structure of celestial bodies. With Earth being the most chemically diverse and fertile out of all the astral bodies known, it is anticipated that the great majority of astromimetic material models will fall in the domain of geo-inspired ones

    One Ion to Rule Them All: Combined Antibacterial, Osteoinductive and Anticancer Properties of Selenite-Incorporated Hydroxyapatite

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    Although hydroxyapatite (HAp) has been doped with dozens of different ions, the quest for an ion imparting a combination of properties conducive to bone healing is still ongoing. Because of its protean potency and the similarity in size and shape to the phosphate tetrahedron, the selenite ion presents a natural ionic substitute in HAp. The incorporation of selenite into synthetic HAp using two different methods – co-precipitation and ion-exchange sorption – was studied for its effect on crystal properties and on a triad of biological responses: antibacterial, anticancer and osteoinductive. Co-precipitation yielded HAp with a higher selenite content than sorption and the stoichiometry of HAp richest in selenite was represented as Ca9.75(PO4)5.75(SeO3)0.25(OH)1.75. The crystallinity of HAp decreased in direct proportion to the amount of selenite incorporated. Because of their lower selenite content, HAp powders prepared by ion-exchange exhibited a consistently higher crystallinity compared to the co-precipitated ones. Annealing partially recovered the crystallinity, yet the difference in crystallinity between powders prepared by co-precipitation and by ion-exchange remained, suggesting that the amorphization is mainly due to structural incorporation of selenite, not its effect on the crystal growth kinetics. The addition of selenite changed the morphology of the HAp nanoparticles from acicular to rounded and affected the crystal lattice parameters in different ways depending on whether the powders were annealed or not. As for the annealed powders, the incorporation of selenite contracted the lattice in both the a and c crystallographic directions. In the agar diffusion assay, the effectiveness of HAp was more dependent on the presence or absence of selenite in it than on its concentration and was the highest against E. coli and S. aureus, moderately high against S. enteritidis and ineffective against P. aeruginosa. In liquid inoculation tests, on the other hand, the antibacterial activity of HAp was directly proportional to the amount of selenite contained in it. The viability of K7M2 osteosarcoma cells decreased in direct proportion to the amount of selenite in HAp and was significantly different from the untreated control and from pure HAp at a content equal to or higher than 1.9 wt%. In contrast, no reduction was observed in the viability of primary fibroblasts treated with HAp incorporating different amounts of selenite ions, suggesting their potentially selective anticancer activity: lethal for cancer cells and harmless for healthy cells. Finally, mRNA expression of the bone gamma-carboxyglutamate protein (BGLAP3) was higher in differentiated MC3T3-E1 osteoblastic cells treated with selenite-incorporated HAp particles than in cells treated with pure HAp. The osteoinductive effect was due to an overall higher metabolic activity of cells treated with the particles and not due to increased proliferation. In such a way, a triad of antibacterial, osteoinductive and anticancer activities was attributed to selenite-incorporated HAp

    Sinuous is a Drosophila claudin required for septate junction organization and epithelial tube size control

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    Epithelial tubes of the correct size and shape are vital for the function of the lungs, kidneys, and vascular system, yet little is known about epithelial tube size regulation. Mutations in the Drosophila gene sinuous have previously been shown to cause tracheal tubes to be elongated and have diameter increases. Our genetic analysis using a sinuous null mutation suggests that sinuous functions in the same pathway as the septate junction genes neurexin and scribble, but that nervana 2, convoluted, varicose, and cystic have functions not shared by sinuous. Our molecular analyses reveal that sinuous encodes a claudin that localizes to septate junctions and is required for septate junction organization and paracellular barrier function. These results provide important evidence that the paracellular barriers formed by arthropod septate junctions and vertebrate tight junctions have a common molecular basis despite their otherwise different molecular compositions, morphologies, and subcellular localizations

    Selective Anticancer Activity of Hydroxyapatite/Chitosan-poly(d,l)-lactide-co-glycolide Particles Loaded with an Androstane-Based Cancer Inhibitor

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    In an earlier study we demonstrated that hydroxyapatite nanoparticles coated with chitosan-poly(d,l)-lactide-co-glycolide (HAp/Ch-PLGA) target lungs following their intravenous injection into mice. In this study we utilize an emulsification process and freeze drying to load the composite HAp/Ch-PLGA particles with 17ÎČ-hydroxy-17α-picolyl-androst-5-en-3ÎČ-yl-acetate (A), a chemotherapeutic derivative of androstane and a novel compound with a selective anticancer activity against lung cancer cells. 1H NMR and 13C NMR techniques confirmed the intact structure of the derivative A following its entrapment within HAp/Ch-PLGA particles. The thermogravimetric and differential thermal analyses coupled with mass spectrometry were used to assess the thermal degradation products and properties of A-loaded HAp/Ch-PLGA. The loading efficiency, as indicated by the comparison of enthalpies of phase transitions in pure A and A-loaded HAp/Ch-PLGA, equaled 7.47 wt.%. The release of A from HAp/Ch-PLGA was sustained, neither exhibiting a burst release nor plateauing after three weeks. Atomic force microscopy and particle size distribution analyses were used to confirm that the particles were spherical with a uniform size distribution of d50 = 168 nm. In vitro cytotoxicity testing of A-loaded HAp/Ch-PLGA using MTT and trypan blue dye exclusion assays demonstrated that the particles were cytotoxic to the A549 human lung carcinoma cell line (46 ± 2%), while simultaneously preserving high viability (83 ± 3%) of regular MRC5 human lung fibroblasts and causing no harm to primary mouse lung fibroblasts. In conclusion, composite A-loaded HAp/Ch-PLGA particles could be seen as promising drug delivery platforms for selective cancer therapies, targeting malignant cells for destruction, while having a significantly lesser cytotoxic effect on the healthy cells

    Implicit Regularization and Renormalization of QCD

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    We apply the Implicit Regularization Technique (IR) in a non-abelian gauge theory. We show that IR preserves gauge symmetry as encoded in relations between the renormalizations constants required by the Slavnov-Taylor identities at the one loop level of QCD. Moreover, we show that the technique handles divergencies in massive and massless QFT on equal footing.Comment: (11 pages, 2 figures

    Hydrothermally processed 1D hydroxyapatite: Mechanism of formation and biocompatibility studies

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    Recent developments in bone tissue engineering have led to an increased interest in one-dimensional (1D) hydroxyapatite (HA) nano- and micro-structures such as wires, ribbons and tubes. They have been proposed for use as cell substrates, reinforcing phases in composites and carriers for biologically active substances. Here we demonstrate the synthesis of 1D HA structures using an optimized, urea-assisted, high-yield hydrothermal batch process. The one-pot process, yielding HA structures composed of bundles of ribbons and wires, was typified by the simultaneous occurrence of a multitude of intermediate reactions, failing to meet the uniformity criteria over particle morphology and size. To overcome these issues, the preparation procedure was divided to two stages: dicalcium phosphate platelets synthesized in the first step were used as a precursor for the synthesis of 1D HA in the second stage. Despite the elongated particle morphologies, both the precursor and the final product exhibited excellent biocompatibility and caused no reduction of viability when tested against osteoblastic MC3T3-E1 cells in 2D culture up to the concentration of 2.6 mg/cm2. X-ray powder diffraction combined with a range of electron microscopies and laser diffraction analyses was used to elucidate the formation mechanism and the microstructure of the final particles. The two-step synthesis involved a more direct transformation of DCP to 1D HA with the average diameter of 37 nm and the aspect ratio exceeding 100:1. The comparison of crystalline domain sizes along different crystallographic directions showed no signs of significant anisotropy, while indicating that individual nanowires are ordered in bundles in the b crystallographic direction of the P63/m space group of HA. Intermediate processes, e.g., dehydration of dicalcium phosphate, are critical for the formation of 1D HA alongside other key aspects of this phase transformation, it must be investigated in more detail in the continuous design of smart HA micro- and nano-structures with advanced therapeutic potentials.This is the peer-reviewed version of the articleStojanović, Z.S., Ignjatović, N., Wu, V., Ćœunič, V., Veselinović, L., Ć kapin, S., Miljković, M., Uskoković, V., Uskoković, D., 2016. Hydrothermally processed 1D hydroxyapatite: Mechanism of formation and biocompatibility studies. Materials Science and Engineering: C 68, 746–757. [https://doi.org/10.1016/j.msec.2016.06.047]Published version: [https://vinar.vin.bg.ac.rs/handle/123456789/7576

    Symmetry preserving regularization with a cutoff

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    A Lorentz and gauge symmetry preserving regularization method is proposed in 4 dimension based on momentum cutoff. We use the conditions of gauge invariance or freedom of shift of the loop-momentum to define the evaluation of the terms carrying Lorentz indices, e.g. proportional to k_{\mu}k_{\nu}. The remaining scalar integrals are calculated with a four dimensional momentum cutoff. The finite terms (independent of the cutoff) are unambiguous and agree with the result of dimensional regularization.Comment: 12 pages, 1 figure, v2 references adde
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