RESUMO
New inorganic nanostructured matrices for fiber-reinforced composites with enhanced high-temperature stability were developed from alkali aluminosilicate polymers doped with different ultra-high-temperature ceramic (UHTC) particles. The alkali aluminosilicate matrices were synthesized at room temperature with a high SiO2:Al2O3 ratio and then further functionalized by doping with 4-5 wt % of micrometric SiC, ZrB2, ZrC, and HfC powders and finally thermally stabilized as glass-ceramics at 750 °C. The different UHTC-doped matrices were characterized according to their dimensional and microstructural changes after thermal cycling in air flux at 1000 °C. The first results showed that carbide-based UHTC powders improved the thermal stability of the matrices, preventing the excessive swelling of the material and the formation of detrimental voids that might result in the lack of adhesion with reinforcing fibers. Contrarily, the addition of ZrB2 resulted in an excessive matrix swelling at high temperature, thus proving no efficacy compared to the undoped matrix. Impregnation tests carried out on C-fiber fabrics showed good processability, adhesion to the fibers, and fracture pull-out, especially for carbide-based matrices.
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AIM: To assess the diagnostic value of apparent diffusion coefficient (ADC) on 3 T device for the prediction of tumoral response to neoadjuvant chemoradiotherapy (nCRT) and for the response assessment after nCRT in patients with locally advanced rectal cancer (LARC), using pathology as a reference. METHODS: Forty-one patients affected by LARC undergoing 3.0 T MRI before and after nCRT were retrospectively selected. After the conventional acquisition of high resolution T2-weighted sequences, diffusion-weighted MRI (DW-MRI) was performed using a spin-echo echo-planar sequence with multiple b values (150, 500, 1000, 1500 s/mm2 ). Fitted ADC values were calculated for each rectal lesion before and after nCRT by drawing a hand-made region of interest (ROI) around the tumour outline. All patients underwent surgery and pathological staging (classified according to tumour regression grading [TRG] and to tumour and node [TN]) represented the reference standard. Pretreatment ADC value (pre-ADC), ADC value obtained after nCRT (post-ADC) and the difference between post-ADC and pre-ADC (ΔADC) were correlated with both the TRG classes and the TN staging system in each patient. RESULTS: The ADC values obtained in the post nCRT examination and the ΔADC were statistically related both to TRG (p = 0.0004; p = 0.0126, respectively) and TN (p = 0.0484; p = 0.0673, respectively) stages at histopathology. On the contrary, the pre-ADC was not related either to the TRG classes or to the lesion TN staging system (p > 0.05). CONCLUSIONS: 3 T DW-MRI using ADC value can be useful to assess the efficacy of nCRT in LARC; in fact, post-ADC and ΔADC values improve MR capability to evaluate tumour response.
Assuntos
Segunda Neoplasia Primária , Neoplasias Retais , Humanos , Imagem de Difusão por Ressonância Magnética/métodos , Neoplasias Retais/diagnóstico por imagem , Neoplasias Retais/terapia , Neoplasias Retais/patologia , Terapia Neoadjuvante/métodos , Estudos Retrospectivos , Resultado do Tratamento , Imageamento por Ressonância Magnética , QuimiorradioterapiaRESUMO
Among the available technologies for ammonium removal from wastewater, ion exchange represents one of the most promising ones in the perspective to recover ammonium and produce a fertilizing product. However, the vast majority of previous studies on ammonium ion exchange did not evaluate the process robustness under real operational conditions nor optimized the desorption step. In this paper, tests of ammonium removal and recovery were conducted on a metakaolin K-based geopolymer, compared with a high-performing Italian natural zeolite in K-form. Real municipal and saline wastewater was treated in a continuous flow pilot plant equipped with a 60-cm adsorption bed (bed volume 203 mL, sorbent mass 145-173 g, empty bed contact time 10 min). Geopolymer granules showed higher performances in terms of selectivity towards ammonium, operating capacity (8.5 mgN g-1 dry adsorbent at an inlet concentration of 40 mgN L-1), bed volumes of wastewater treated at the selected breakpoint (149). Geopolymer resulted to be a cost-effective adsorbent for wastewater treatment capable to adsorb cations by ion exchange, allowing a fractionated desorption procedure that led to recover ammonium in a solution composed mainly by NH4NO3 (37%wt) and KNO3 (56%wt), potentially usable as fertilizer. The geopolymer robustness was assessed after repeated adsorption/regeneration cycles showing that the geopolymer mechanical and morphological properties did not deteriorate. The results make the tested geopolymer a very promising material for the optimization and scale-up of the ammonium recovery process in a circular economy perspective.
Assuntos
Compostos de Amônio , Zeolitas , Águas Residuárias , Troca Iônica , Fertilizantes , AdsorçãoRESUMO
In this paper, four near-net shaped foams were produced via direct foaming, starting from a benchmark metakaolin-based geopolymer formulation. Hydrogen peroxide and metallic silicon were used in different amounts as blowing agents to change the porosity from meso- to ultra-macro-porosity. Foams were characterized by bulk densities ranging from 0.34 to 0.66 g cm-3, total porosity from 70% to 84%, accessible porosity from 41% to 52% and specific surface area from 47 to 94 m2 g-1. Gas permeability tests were performed, showing a correlation between the pore features and the processing methods applied. The permeability coefficients k1 (Darcian) and k2 (non-Darcian), calculated applying Forchheimer's equation, were higher by a few orders of magnitude for the foams made using H2O2 than those made with metallic silicon, highlighting the differing flow resistance according to the interconnected porosity. The gas permeability data indicated that the different geopolymer foams, obtained via direct foaming, performed similarly to other porous materials such as granular beds, fibrous filters and gel-cast foams, indicating the possibility of their use in a broad spectrum of applications.
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Geopolymer beads, conceived as alternative low cost adsorbents for wastewater treatment, were shaped by a dripping technique in liquid nitrogen, through an ice-templating process. PEG600 was added as a binder to ease the process, standardizing the beads dimension. The beads were investigated in terms of morphology, microstructure and mechanical strength, following compressive tests by ISO 18591. Functional tests, to verify the adsorption capacity, were conducted using methylene blue (MB) with different concentrations and for different contact time. The removal efficiency was mainly related to the morphology and porosity of the beads, which in turn was directly related to the water content added to the geopolymer slurry. In general, all beads reached an average removal efficiency of 98% after 24 h. However, the best performing beads were able to uptake MB very quickly, attaining a removal efficiency of 76% after only 30 min.
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The 3-D spatial and mechanical features of nano-topography can create alternative environments, which influence cellular response. In this paper, murine fibroblast cells were grown on surfaces characterized by protruding nanotubes. Cells cultured on such nano-structured surface exhibit stronger cellular adhesion compared to control groups, but despite the fact that stronger adhesion is generally believed to promote cell cycle progression, the time cells spend in G1 phase is doubled. This apparent contradiction is solved by confocal microscopy analysis, which shows that the nano-topography inhibits actin stress fiber formation. In turn, this impairs RhoA activation, which is required to suppress the inhibition of cell cycle progression imposed by p21/p27. This finding suggests that the generation of stress fibers, required to impose the homeostatic intracellular tension, rather than cell adhesion/spreading is the limiting factor for cell cycle progression. Indeed, nano-topography could represent a unique tool to inhibit proliferation in adherent well-spread cells.
Assuntos
Adesão Celular , Ciclo Celular , Fibroblastos/fisiologia , Nanoestruturas/química , Animais , Divisão Celular , Células Cultivadas , Inibidor de Quinase Dependente de Ciclina p21/metabolismo , Fibroblastos/citologia , Camundongos , Alicerces Teciduais , Proteínas rho de Ligação ao GTP/metabolismo , Proteína rhoA de Ligação ao GTPRESUMO
Porous macro-granules of nanostructured apatite with Ca ions partially cosubstituted with Mg and Sr ions in different ratios (SrMgHAs), were synthesized at 37°C and compared with Mg and/or Sr free apatites (MgHAs and HA). Strontium improved the Mg substitution extent in the apatite and the chemical-physical and thermal stability of the resulting cosubstituted apatite. Porous macro-granules of 400-600 micron with selected composition were tested for the ionic release in synthetic body fluid and the data were related with the results of preliminary cell investigation in vitro. As compared to the corresponding Sr-free granulate, the SrMgHA could be exploited to prolong the beneficial Mg release during the bone regeneration process. In addition the contemporary in situ supply of Sr, an antiosteoporotic and anticarie ion, could influence the quality of new hard tissues. The ionic multirelease created a more favorable environment for human osteoblasts, demonstrated by a proliferative effect for each dose tested in the range 0.1-10 mg/mL.
Assuntos
Substitutos Ósseos/química , Durapatita/química , Regeneração Óssea/efeitos dos fármacos , Substitutos Ósseos/administração & dosagem , Substitutos Ósseos/farmacologia , Proliferação de Células/efeitos dos fármacos , Células Cultivadas , Relação Dose-Resposta a Droga , Durapatita/administração & dosagem , Durapatita/farmacologia , Humanos , Magnésio/química , Teste de Materiais , Osteoblastos/citologia , Osteoblastos/efeitos dos fármacos , Osteoporose/terapia , PorosidadeRESUMO
In this study, rapid CAD-CAM prototyping of pure hydroxyapatite to replace temporomandibular joint condyles was tested in sheep. Three adult animals were implanted with CAD-CAM-designed porous hydroxyapatite scaffolds as condyle substitutes. The desired scaffold shape was achieved by subtractive automated milling machining (block reduction). Custom-made surgical guides were created by direct metal laser sintering and were used to export the virtual planning of the bone cut lines into the surgical environment. Using the same technique, fixation plates were created and applied to the scaffold pre-operatively to firmly secure the condyles to the bone and to assure primary stability of the hydroxyapatite scaffolds during masticatory function. Four months post-surgery, the sheep were sacrificed. The hydroxyapatite scaffolds were explanted, and histological specimens were prepared. Different histological tissues penetrating the scaffold macropores, the sequence of bone remodeling, new apposition of bone and/or cartilage as a consequence of the different functional anatomic role, and osseointegration at the interface between the scaffold and bone were documented. This animal model was found to be appropriate for testing CAD-CAM customization and the biomechanical properties of porous, pure hydroxyapatite scaffolds used as joint prostheses.
Assuntos
Substitutos Ósseos/uso terapêutico , Durapatita/uso terapêutico , Côndilo Mandibular/cirurgia , Ovinos/cirurgia , Alicerces Teciduais/química , Animais , Substitutos Ósseos/química , Desenho Assistido por Computador , Durapatita/química , Côndilo Mandibular/patologia , Porosidade , Procedimentos de Cirurgia Plástica/métodosRESUMO
The development of advanced materials with biomimetic features in order to elicit desired biological responses and to guarantee tissue biocompatibility is recently gaining attention for tissue engineering applications. Bioceramics, such as hydroxyapatite-based biomaterials are now used in a number of different applications throughout the body, covering all areas of the skeleton, due to their biological and chemical similarity to the inorganic phases of bones. When bioactive sintered hydroxyapatite (HA) is desired, biomolecular modification of these materials is needed. In the present work, we investigated the influence of plasma surface modification coupled to chemical grafting on the cell growth compliance of HA 3D scaffolds.
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Divisão Celular , Durapatita/química , Gases em Plasma , Alicerces Teciduais , Materiais Biocompatíveis , Células Cultivadas , Corantes Fluorescentes/química , Humanos , Microscopia Eletrônica de Varredura , Espectrometria de Fluorescência , Propriedades de Superfície , Difração de Raios XRESUMO
We report the identification of a novel partner of Kidins220/ARMS (Kinase D-interacting substrate of 220 kDa/Ankyrin Repeat-rich Membrane Spanning) an adaptor of neurotrophin receptors playing crucial roles during neurogenesis. Screening a phage display library of brain cDNA products we found that D. rerio Pdzrn3, a protein containing RING-finger and PDZ-domains, interacts with Kidins220/ARMS through its first PDZ-domain. Both zebrafish proteins share high homology with the corresponding mammalian proteins and both genes are developmentally expressed in neural districts where early neurogenesis occurs. The interaction was also confirmed by biochemical assays and by co-localization at the tips of growing neurites of PC12 cells induced with nerve growth factor.
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Proteínas de Transporte/química , Proteínas de Transporte/metabolismo , Proteínas de Membrana/metabolismo , Proteínas do Tecido Nervoso/metabolismo , Sequência de Aminoácidos , Animais , Biologia Computacional , Células HEK293 , Humanos , Proteínas de Membrana/química , Camundongos , Dados de Sequência Molecular , Proteínas do Tecido Nervoso/química , Células PC12 , Ligação Proteica , Estrutura Terciária de Proteína , Ratos , Ubiquitina-Proteína Ligases , Proteínas de Peixe-Zebra/química , Proteínas de Peixe-Zebra/metabolismoRESUMO
The use of magnetic activation has been proposed to answer the growing need for assisted bone and vascular remodeling during template/scaffold regeneration. With this in mind, a synthesis procedure was developed to prepare bioactive (Fe2+/Fe3+)-doped hydroxyapatite (Fe-HA), endowed with superparamagnetic-like properties. This new class of magnetic hydroxyapatites can be potentially employed to develop new magnetic ceramic scaffolds with enhanced regenerative properties for bone surgery; in addition, magnetic Fe-HA can find application in anticancer therapies, to replace the widely used magnetic iron oxide nanoparticles, whose long-term cytotoxicity was recently found to reach harmful levels. An extensive physicochemical, microstructural and magnetic characterization was performed on the obtained Fe-HA powders, and demonstrated that the simultaneous addition of Fe2+ and Fe3+ ions during apatite nucleation under controlled synthesis conditions induces intrinsic magnetization in the final product, minimizing the formation of magnetite as secondary phase. This result potentially opens new perspectives for biodevices aimed at bone regeneration and for anti-cancer therapies based on hyperthermia.
Assuntos
Materiais Biocompatíveis/química , Durapatita/química , Temperatura Alta , Ferro/química , Magnetismo , Animais , Materiais Biocompatíveis/farmacologia , Adesão Celular/efeitos dos fármacos , Durapatita/farmacologia , Ferro/farmacologia , Campos Magnéticos , Microscopia Eletrônica de Transmissão , Microscopia de Fluorescência , Osteoblastos/citologia , Osteoblastos/efeitos dos fármacos , Oxirredução/efeitos dos fármacos , Pós , Coelhos , Espectroscopia por Absorção de Raios X , Difração de Raios XRESUMO
An efficient method for the direct and covalent decoration of granules of nanostructured apatite with a sample monosaccharide is presented; the hydroxyapatite material was directly functionalised with a short azido-containing spacer arm, to which α-propargyl glucopyranoside has been chemoselectively ligated by Huisgen-type cycloaddition. The 'glycosylated' hydroxypatite was characterised by its ability to interact with glucose recognising lectins.
Assuntos
Materiais Biocompatíveis/síntese química , Substitutos Ósseos/síntese química , Durapatita/química , Glicoconjugados/síntese química , Glicosídeos/química , Monossacarídeos/química , Engenharia Tecidual/métodos , Azidas/química , Química Click , Lectinas/metabolismo , Nanoestruturas/química , Ligação Proteica , Espectroscopia de Infravermelho com Transformada de Fourier , EstereoisomerismoRESUMO
The functional behavior of synthetic apatite, commonly used as fillers or scaffolds, depends on physical and chemical parameters, which vary in response to chemical substitutions and to thermal treatments. The effect of silicon co-substituting with carbonate ions in the apatite lattice on the properties of the as-synthesized powder and finally on human osteoblast in vitro behavior was investigated. Dose-response curves of Si-free and Si-substituted carbonated apatites (namely CHA and SiCHA-1 and SiCHA-2 with 0.88 and 0.55 wt % of Si, respectively) showed that SiCHA-1 had toxic effect, whereas CHA and SiCHA-2, at worst, hindered osteoblast proliferation, but no toxicity occurred. Subsequent experiments compared the effects of CHA and SiCHA-2 used at the doses of 0.3 and 1 mg/mL. After 7 days of treatment, both the powders stimulated cell proliferation and protein content and inhibited alkaline phosphatase activity. However, SiCHA-2 slightly stimulated osteoblast differentiation, as shown by higher calcium deposition, compared with CHA. The cell behaviors were linked to the peculiar powder characteristics. The as-synthesized powder represents the most critical system in terms of reactivity toward cells and can inform on the limits for positively exploiting the characteristics of SiCHA powders in making bone fillers or scaffolds, using no thermal treatments. (c) 2010 Wiley Periodicals, Inc. J Biomed Mater Res, 2010.
Assuntos
Apatitas/farmacologia , Carbonatos/farmacologia , Materiais Revestidos Biocompatíveis/farmacologia , Osteoblastos/efeitos dos fármacos , Osteoblastos/metabolismo , Compostos de Silício/farmacologia , Adulto , Animais , Apatitas/química , Cálcio/metabolismo , Carbonatos/química , Bovinos , Diferenciação Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Materiais Revestidos Biocompatíveis/química , Relação Dose-Resposta a Droga , Humanos , Masculino , Teste de Materiais , Osteoblastos/citologia , Compostos de Silício/química , Propriedades de SuperfícieRESUMO
This work deals with the preparation of bioactive ceramic composites to be employed for the development of load-bearing bone substitutes, made of hydroxyapatite (Ca(10)(PO(4))(6)(OH)(2), HA) and bioactive dicalcium silicate (Ca(2)SiO(4), C(2)S) as a reinforcing phase. The composite materials were prepared by Fast Hot-Pressing (FHP), which allowed the rapid sintering of monolithic ceramics at temperatures up to 1500 degrees C, well above the commonly adopted temperatures for the consolidation of hydroxyapatite (1200-1300 degrees C). The purpose was to achieve the grain coalescence of both HA and the strengthening phase, so that to obtain a homogeneous ceramic material characterized by controlled phase composition and improved mechanical strength; the dwell time was reduced as much as possible to prevent HA decomposition and excessive grain growth. The most remarkable result, in terms of phase composition, was the absence of any secondary phases in the final ceramics other than HA and C(2)S, even after sintering at 1500 degrees C. The flexure strength of the composite materials was found to be much higher than that of HA alone. Further mechanical characterization was also carried out on HA and composites, sintered in different conditions, to evaluate the elastic properties and fracture toughness, and properties close to those of mineral bone were found. These preliminary results confirmed that composites of HA and Ca(2)SiO(4) are promising for the development of bioactive load-bearing ceramic bone substitutes with controlled phase composition.
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Osso e Ossos/fisiologia , Compostos de Cálcio/química , Durapatita/química , Silicatos/química , Alicerces Teciduais/química , Fenômenos Biomecânicos , Osso e Ossos/citologia , Fenômenos Químicos , Temperatura , Suporte de Carga , Difração de Raios XRESUMO
Neuronal CIPP (channel-interacting PDZ protein) is a multivalent PDZ protein that interacts with specific channels and receptors highly expressed in the brain. It is composed of four PDZ domains that behave as a scaffold to clusterize functionally connected proteins. In the present study, we selected a set of potential CIPP interactors that are involved directly or indirectly in mechanisms of cytoskeletal remodelling and membrane protrusion formation. For some of these, we first proved the direct binding to specific CIPP PDZ domains considered as autonomous elements, and then confirmed the interaction with the whole protein. In particular, the small G-protein effector IRSp53 (insulin receptor tyrosine kinase substrate protein p53) specifically interacts with the second PDZ domain of CIPP and, when co-transfected in cultured mammalian cells with a tagged full-length CIPP, it induces a marked reorganization of CIPP cytoplasmic localization. Large punctate structures are generated as a consequence of CIPP binding to the IRSp53 C-terminus. Analysis of the puncta nature, using various endocytic markers, revealed that they are not related to cytoplasmic vesicles, but rather represent multi-protein assemblies, where CIPP can tether other potential interactors.
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Proteínas de Transporte/metabolismo , Citoesqueleto/metabolismo , Animais , Western Blotting , Encéfalo/metabolismo , Proteínas de Transporte/genética , Linhagem Celular , Cromatografia de Afinidade , Citosol/metabolismo , Humanos , Imunoprecipitação , Camundongos , Microscopia de Fluorescência , Proteínas do Tecido Nervoso/genética , Proteínas do Tecido Nervoso/fisiologia , Ligação Proteica , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por MatrizRESUMO
With the ultimate goal to generate suitable materials for the repair of osteochondral defects, in this work we aimed at developing composite osteochondral scaffolds organized in different integrated layers, with features which are biomimetic for articular cartilage and subchondral bone and can differentially support formation of such tissues. A biologically inspired mineralization process was first developed to nucleate Mg-doped hydroxyapatite crystals on type I collagen fibers during their self-assembling. The resulting mineral phase was non-stoichiometric and amorphous, resembling chemico-physical features of newly deposited, natural bone matrix. A graded material was then generated, consisting of (i) a lower layer of the developed biomineralized collagen, corresponding to the subchondral bone, (ii) an upper layer of hyaluronic acid-charged collagen, mimicking the cartilaginous region, and (iii) an intermediate layer of the same nature as the biomineralized collagen, but with a lower extent of mineral, resembling the tidemark. The layers were stacked and freeze-dried to obtain an integrated monolithic composite. Culture of the material for 2 weeks after loading with articular chondrocytes yielded cartilaginous tissue formation selectively in the upper layer. Conversely, ectopic implantation in nude mice of the material after loading with bone marrow stromal cells resulted in bone formation which remained confined within the lower layer. In conclusion, we developed a composite material with cues which are biomimetic of an osteochondral tissue and with the capacity to differentially support cartilage and bone tissue generation. The results warrant testing of the material as a substitute for the repair of osteochondral lesions in orthotopic animal models.
Assuntos
Materiais Biomiméticos , Cartilagem Articular/metabolismo , Condrócitos/fisiologia , Engenharia Tecidual/métodos , Alicerces Teciduais , Animais , Materiais Biocompatíveis/química , Materiais Biocompatíveis/metabolismo , Cartilagem Articular/química , Cartilagem Articular/citologia , Condrócitos/citologia , Colágeno/química , Colágeno/metabolismo , Humanos , Ácido Hialurônico/química , Ácido Hialurônico/metabolismo , Teste de Materiais , CamundongosRESUMO
A cryogenic process, including freeze-casting and drying has been performed to obtain hydroxyapatite (HA) scaffolds (approx. diameter 10 mm, height 20 mm) with completely lamellar morphology due to preferentially aligned channel-like pores. Changing the process parameters that influence the cold transmission efficiency from the bottom to the top of the poured HA slurry, lamellar ice crystals with different thickness grew throughout the samples. After sintering, scaffolds with porosity features nearly resembling the ice ones were obtained. The interconnection of pores and the ability of the scaffolds to be rapidly penetrated by synthetic body fluid has been proven. Biohybrid HA/gel composites were prepared, infiltrating HA lamellar scaffolds (45-55 vol.% of porosity) with a 10wt.% solution of gelatine. Colouring genipine was used to cross-link gelatine and clearly show the distribution of the protein in the composite. The compressive mechanical properties of lamellar scaffolds improved with the addition of gelatine: the strength increased up to 5-6 times, while the elastic modulus and strain approximately doubled. The effectiveness of the cross-linkage has been preliminarily verified following scaffold degradation in synthetic body fluid.
Assuntos
Materiais Biocompatíveis/química , Substitutos Ósseos , Durapatita/química , Gelatina/química , Animais , Força Compressiva , Reagentes de Ligações Cruzadas/farmacologia , Gelo , Microscopia Eletrônica de Varredura/métodos , Porosidade , Pós , Estresse Mecânico , Suínos , Temperatura , Difração de Raios XRESUMO
Sr and CO3 co-substituted hydroxyapatite (SrCHA) nanopowder was synthesized by neutralization. The powder was characterized. The improved solubility in Hanks' balanced solution of SrCHA granules (400-600 microm of dimensional range), potentially usable as bone filler, was assessed and compared with that of an analogous carbonate free granulate. SrCHA porous bodies with interconnected micro- and macro-porosity, which mimic the morphology of spongy bone, were prepared by the impregnation of cellulose sponges with suspensions of the SrCHA powder and controlled sintering. SrCHA porous scaffolds sintered at 850 degrees C, in flowing CO2 atmosphere, showed satisfying compressive strength (4.58+/-0.75 MPa) for a porosity value of 45 vol.% and retained the desired ionic substitutions (Sr/Ca=0.11 and CO3=6.8 wt.%). The possibility of widely modulating, by acting on the chemical-physical-geometrical features of the material, the prolonged in situ release of therapeutic Sr, together with the fundamental (Ca, PO4) and main substituting (CO3) ions that constitute the bone mineral phase, makes the use of SrCHA as resorbable bone filler or bone substitute scaffolds promising, especially when pathologies related with Sr deficiency are present. In vitro and in vivo tests are in progress.
Assuntos
Carbonatos/química , Durapatita/síntese química , Teste de Materiais , Estrôncio/química , Força Compressiva , Análise Diferencial Térmica , Concentração de Íons de Hidrogênio , Microscopia Eletrônica de Varredura , Porosidade , Pós/síntese química , Solubilidade , Espectroscopia de Infravermelho com Transformada de Fourier , Condutividade Térmica , Termogravimetria , Difração de Raios XRESUMO
The incorporation of magnesium ions (in the range 5-10 mol% in respect to Ca) into the hydroxyapatite structure, which is of great interest for the developing of artificial bone, was performed using magnesium chloride, calcium hydroxide and phosphoric acid, as reactants. Among the synthesized powders, the synthetic HA powder containing 5.7% Mg substituting for calcium was selected, due to its better chemico-physical features, and transformed into granules of 400-600 microm, for biocompatibility tests (genotoxicity, carcinogenicity, toxicity, in vitro cytotoxicity and in vivo skin irritation-sensitization tests). In vivo tests were carried out on New Zealand White rabbits using the granulate as filling for a femoral bone defect: osteoconductivity and resorption were found to be enhanced compared to commercial stoichiometric HA granulate, taken as control.
Assuntos
Biomimética , Durapatita/química , Magnésio/química , Animais , Materiais Biocompatíveis/química , Osso e Ossos/ultraestrutura , Hidróxido de Cálcio/química , Concentração de Íons de Hidrogênio , Cloreto de Magnésio/química , Teste de Materiais , Microscopia Eletrônica de Varredura , Ácidos Fosfóricos/química , Coelhos , Espectroscopia de Infravermelho com Transformada de Fourier , Difração de Raios XRESUMO
PDZ (acronym of the synapse-associated protein PSD-95/SAP90, the septate junction protein Discs-large, and the tight junction protein ZO-1) domains are abundant small globular protein interaction domains that mainly recognize the carboxyl termini of their target proteins. Detailed knowledge on PDZ domain binding specificity is a prerequisite for understanding the interaction networks they establish. We determined the binding preference of the five PDZ domains in the protein tyrosine phosphatase PTP-BL by screening a random C-terminal peptide lambda phage display library. Interestingly, the potential of PDZ2 to interact with class III-type ligands was found to be modulated by the presence of PDZ1. Structural studies revealed a direct and specific interaction of PDZ1 with a surface on PDZ2 that is opposite the peptide binding groove. Long-range allosteric effects that cause structural changes in the PDZ2 peptide binding groove thus explain the altered PDZ2 binding preference. Our results experimentally corroborate that the molecular embedding of PDZ domains is an important determinant of their ligand binding specificity.