Bioactive glasses undergo dynamic changes in vivo to produce an apatite layer permitting a strong bond with living tissues including both bone and soft tissues, and their compositions can be modified and tailored. The aim of this project was to generate high phosphate low fluoride containing bioactive glasses and explore their bioactivity and biological performances in vitro. Bioactive glasses (0-7% F- content, constant 6.33% P2O5 in Mol.%) were produced and the particles immersed in Tris Buffer solution or cell culture medium (α-MEM) to determine apatite formation and ion (Ca, P, Si and F) release. Bioactive glass conditioned medium was used to treat pre-osteoblasts MC3T3-E1 for cytotoxicity, pre-osteogenic and pro-angiogenic responses, and to human oral fibroblasts and epithelial cells for proliferation. Antibacterial ability was explored by incubating supra- and sub-gingival bacteria with bioactive glass particulates. Rapid apatite formation was observed in F- containing bioactive glasses after only 2 h immersion in Tris buffer solution, while it was not detectable until 72 h in the F- free bioactive glass. Alkaline phosphatase activity, cell number, collagen formation, bone-like mineral nodules and osteogenic gene expression of MC3T3-E1 cells were significantly promoted in low F- bioactive glass (P6.33F1) conditioned medium. MC3T3-E1 VEGF gene expression was increased, and protein production was dose-dependently promoted with F- containing bioactive glass conditioned medium, which also promoted human oral fibroblast proliferation, but suppressed epithelial cell numbers. After incubation with glass particulates, the growth of L. casei, S. mitis, A. actinomycetemcomitans and P. gingivalis, was significantly inhibited; the antibacterial activity being dependent on the F- content of the bioactive glasses. As a potential bone graft substitute in vivo, such novel bioactive glasses would be expected to stimulate bone formation and overcome problems associated with infection and the poor vascularisation in large bone graft sites. Additionally, they could reduce the need for further clinical intervention, and in particular, will be advantageous for the periodontal soft tissue regeneration.

No description available.

The objective of this research is to synthesize and characterize microstructures and some elastic properties of bioactive glasses subject to relaxation and/or devitrification treatments. We synthesize two kinds of bioglasses, i.e. P-richer 45S5 and P-poorer 55S4.3. After tempering, the as-prepared bioactive glasses are transparent, 55S4.3 being colorless while 45S5 pale pink in color. The thermal events in DTA analysis indicated that the crystallization of 45S5 and 55S4.3 starts at 620oC and 680oC, respectively. The two bioactive glasses became ivory upon heating at 715oC, and the degree of being opaque increases with dwelling time. The crystalline phase for 45S5 is Na2CaSiO4 -derived Na2Ca2Si3O9 or Na4CaSi3O9. By XRD traces and polarizing optical micrographs, we conclude that the crystal is based on simple cubic structure with a=7.5054Å and space group P213 (198). Due to poor crystallization rate, the crystal in P-poor 55S4.3 glass was not investigated in detail. However, according to the similarity of Raman spectra for devitrified 45S5 and 55S4.3, we suggest that the crystal is similar for the two devitrified glasses. Raman spectra indicated that the relaxed 45S5 has predominant Q2 and Q3 species and the Q3/Q2 ratio decreases with firing time at 715oC. As for relaxed 55S4.3, the major structural unit is Q3, and the intensity of Q3 is higher for 55S4.3 than 45S5. As the Na+/Si4+ ratio increases, the intensity of 946 (or 947) cm-1 increases while bands near 1100 cm-1 decrease. Based on the Raman spectra of devitrified 45S5 and 55S4.3, the crystals in the two glasses have a common structural unit of SiO32- (Q2). The elasticity measurement by Brillouin scattering indicated that the moduli for devitrified glass 45S5 are greater than undevitrified 45S5 and 55S4.3 glass. The elasticity of the present bioactive glasses is lower than hydroxyapatite and fluorapatite.

Bioactive glasses are a class of synthetic inorganic material that have wide orthopedics, dentistry, tissue engineering and other biomedical applications. The origin of the bioactivity is closely related to the atomic structures of these novel glass materials, which otherwise lack long range order and defies any direct experimental measurements due to their amorphous nature. The structure of bioactive glasses is thus essential for the understanding of bioactive behaviors and eventually rational design of glass compositions. In this dissertation, molecular dynamics (MD) and reverse monte carlo (RMC) based computer simulations have been used to systematically study the atomic structure of three classes of new bioactive glasses: strontium doped 45S5 Bioglass®, ZnO-SrO containing bioactive glasses, and Cao-MgO-P2O5-SiO2 bioactive glasses. Properties such as ionic diffusion that are important to glass dissolution behaviors are also examined as a function of glass compositions. The accuracy of structure model generated by simulation was validated by comparing with various experimental measurements including X-ray/neutron diffraction, NMR and Raman spectroscopy. It is shown in this dissertation that atomistic computer simulations, when integrated with structural and property characterizations, is an effective tool in understanding the structural origin of bioactivity and other properties of amorphous bioactive materials that can lead to design of novel materials for biomedical applications.

Made available in DSpace on 2017-07-21T19:25:46Z (GMT). No. of bitstreams: 1 Iolanda Cristina Dechandt.pdf: 4265751 bytes, checksum: 63e41222d90f6a9011f71a3cac7991d8 (MD5) Previous issue date: 2015-03-06 / Fundação Araucária de Apoio ao Desenvolvimento Científico e Tecnológico do Paraná / Progress in medicine has led to an increase in life expectancy of the world population. On the other hand, the properties of certain tissues and organs that compose the human body continues to follow the aging process. Faced with this challenge, biomaterial are developed with new technologies for bone substitutes. In this study we investigated the bioactivity of the glasses system 2Na2O.1CaO.3SiO2 with 0, 3 and 6% P2O5 in weight. The bioactivity was studied by immersion in simulated body fluid solution. Heat treatments were also performed in order to study the bioactivity of these glass-ceramics. Differential scanning calorimetry was performed to determine the glass transition temperatures for the glasses. Through Fourier transform infrared spectroscopy analysis was used to verify the bioactivity. The hardness and elastic modulus of the glasses were determined by the instrumented nanoindentation. X-ray diffraction confirmed the crystalline phases present in the glass ceramic samples. It was observed the formation of a hydroxycarbonate apatite layer after 21 days in samples of glass 2Na2O.1CaO.3SiO2 with 0, 3 and 6% P2O5 in weight. The best condition for the growth of hydroxycarbonate apatite layer in the glass-ceramics was the 2Na2O.1CaO.3SiO2 + 3% P2O5 that received heat treatment of 15 hours at 560° C. We observed the growth of the hydroxycabonate apatite layer after 7 days, and the glass-ceramic 2Na2O.1CaO.3SiO2+6% P2O5 who received heat treatment of 15 hours at 560° C the hydroxycabonate apatite layer was observed after 14 days in vitro novel. It was observed that cristalyzation is reduced with increase P concentration. At glass-ceramics with 6%wt of P2O5 the crystals are richer in Ca than in the stoichiometric glass matrix. In opposition, for 1Na2O2NaO3SiO2 glass-ceramics, the crystals are richer in Na.x / Os avanços na medicina vêm levando a um aumento na expectativa de vida da população mundial, por outro lado o desgaste de certas propriedades de tecidos e órgãos que compõe o corpo humano continua acompanhando o processo de envelhecimento. Frente a esse desafio os biomateriais são desenvolvidos com novas tecnologias para substituir ossos. Nesta pesquisa investigamos a bioatividade dos vidros no sistema 2Na2O.1CaO.3SiO2-P2O5 com 0, 3 e 6% em peso de P2O5. A bioatividade foi investigada pela imersão das amostras em solução de fluido corpóreo simulado. Realizados tratamentos térmicos a fim de verificar a bioatividade em vitrocerâmicas. Por meio da calorimetria exploratória diferencial determinamos os valores de temperatura de transição vítrea dos vidros. Através das análises de Infravermelho por transformada de Fourier pudemos verificar a bioatividade dos vidros. Analises de indentação instrumentada determinaram a dureza e o módulo de elasticidade dos vidros. A difração de raios X nos forneceu as fases cristalinas presentes nas amostras vitrocerâmicas. Foi verificado a formação de uma camada de hidroxicarbonato de apatita após 21 dias nas amostras de vidro 2Na2O.1CaO.3SiO2 com 0, 3 e 6% em peso de P2O5. A melhor condição para o crescimento da camada de hidroxicarbonato de apatita nos vitrocerâmicos foi 2Na2O.1CaO.3SiO2 + 3% P2O5 que recebeu tratamento térmico por 15 horas a 560°C. Nos observamos a camada de hidroxiapatita após 7 dias, e o vitrocerâmico 2Na2O.1CaO.3SiO2+6% P2O5 que recebeu tratamento por 15 horas a camada hidroxiapatita foi observada após 14 dias de ensaio in vitro. Foi observado que a cristalização é reduzida com o aumento da concentração de P. No vitrocerâmico com 6% em peso de P2O5 os cristais são mais ricos em Ca do que na matriz vítrea estequiométrica. Por outro lado, o vitrocerâmico com a fase 1Na2O2NaO3SiO2 os cristais são ricos em Na.

Στην παρούσα εργασία η ενασχόλησή μας αφορούσε τη σύνθεση και τον χαρακτηρισμό βιοενεργών γυαλιών. Οι συνθέσεις που πραγματοποιήθηκαν ήταν καθαρής SiO2, μικτών γυαλιών SiO2–ΜΟ (Μ=Ca, Mg) αλλά επίσης και γυαλιών σύστασης SiO2 –CaΟ–P2O5. Πραγματοποιήθηκαν παρασκευές με διάφορα ποσοστά τροποποιητών (Ca, Mg). Μετά την παρασκευή των υλικών ακολούθησε ο φυσικοχημικός χαρακτηρισμός τους με διάφορες τεχνικές όπως: προσδιορισμός ειδικής επιφάνειας και όγκου πόρων (ΒΕΤ), ηλεκτρονική μικροσκοπία σάρωσης (SEM), θερμοσταθμική ανάλυση (TGA), περίθλαση ακτίνων Χ (XRD) και φασματοσκοπία απορρόφησης υπερύθρου (IR). Μετά ακολούθησε μελέτη της βιοενεργότητας με εμβάπτιση σε διάλυμα SBF. Τα αποτελέσματα έδειξαν ότι τα γυαλιά που παρασκευάστηκαν είχαν μεσοπορώδη δομή ενώ όσον αφορά τη βιοενεργότητα τα γυαλιά σύστασης SiO2–CaO and SiO2–CaΟ–P2O5 προκάλεσαν σχηματισμό απατίτη στην επιφάνειά τους. / In the present thesis our work was focused on the study of the synthesis and characterization of bioactive glasses. Pure SiO2 and mixed glasses composed of SiO2–ΜΟ (Μ=Ca, Mg) and SiO2–CaΟ–P2O5 were prepared using different amounts of modifiers (Ca, Mg). Next the prepared materials were characterized by using various techniques such as: BET, SEM, TGA, XRD and IR. Finally their bioactivity was studied in vitro after immersion in SBF solution. It was found that the prepared materials showed a mesoporous structure. Regarding the bioactivity glasses with compositions of SiO2–CaO and SiO2–CaΟ–P2O5 induced the formation of apatite layer on their surface.

Dans ce travail, nous avons élaboré, par voie sol-gel, un nouveau verre bioactif mésoporeux : 92S6 (92% SiO2, 6% CaO, et 2% P2O5). Cette synthèse a été développée en variant les paramètres telles que la température, la nature du tensioactif (ionique (le CTAB) ou non ionique (le P123)) et la longueur de la chaîne carbonée pour chaque type de tensioactif et en étudiant leurs effets sur les propriétés texturales du verre. Des études physico-chimiques et biologiques in vitro ont été menées sur ces biomatériaux. Par la suite, nous avons réalisé une étude structurale de l'eau confinée dans les pores du verre synthétisé qui a révélé une modification de l'ordre locale en comparaison avec l'état massique (bulk). Ceci permet un contrôle de la quantité de principe actif à incorporer dans les pores, du taux d'adsorption et de la cinétique de libération. La diffraction des Rayons X aux petits angles, l'analyse texturale par BET et les images de la microscopie électronique en transmission ont mis en évidence l'influence des paramètres de synthèse sur les propriétés texturales des verres synthétisés. En effet, l'échantillon synthétisé avec le tensioactif ionique (CTAB) présente une structure mésoporeuse non ordonné, alors que l'utilisation du tensioactif non-ionique (P123) favorise l'obtention d'un verre mésoporeux ayant une structure poreuse ordonnée. Dans le cas des verres synthétisés avec les différentes longueurs de la chaîne carbonée des tensioactifs, nous avons démontré que la longueur de la chaîne alkyle du tensioactif ionique détermine la morphologie des particules et les caractéristiques texturales des 3 verres, alors que nous avons noté une absence de différences significatives dans la texture des matériaux dans le cas des 3 verres synthétisés avec les tensioactifs non ioniques. Nous avons aussi mis en évidence l'influence de la température de synthèse sur les propriétés texturales des verres synthétisés. Nous avons démontré que la température de synthèse agit sur le diamètre des pores de manière différente selon la nature du tensioactif. L'augmentation de la température de synthèse conduit à une augmentation de la dimension des cavités dans le cas des verres synthétisés avec le P123, alors que dans le cas des verres synthétisés avec le tensioactif ionique CTAB, l'augmentation de la température de synthèse conduit à une diminution des diamètres des pores. Nous avons démontré que la morphologie des particules et les caractéristiques texturales des verres influent sur la bioactivité de ces derniers. Nous avons obtenu des verres bioactifs comme en témoigne la formation de la couche d'hydroxyapatite à leurs surfaces une fois immergés dans le SBF, ce qui explique l'intérêt des ces verres dans le domaine de la chirurgie orthopédique. / In this study, a new mesoporous bioactive glass 92S6 (92% SiO2, 6% CaO, and 2% P2O5), was prepared by sol-gel method. The purpose of this study was first to investigate the effect of synthesis parameters such as aging temperature, surfactant type and surfactant carbon chain length on the glass textural properties and then to investigate these effect on the glass bioactivity. Then, we conducted a structural study of water confined in the pores of the synthesized glass. This study revealed a change of the local order of confined water in comparison with the bulk. This allows control of drugs to be incorporated into the pores, the adsorption rate and the release kinetics. The small-angle XRD patterns (SAXRD), the Brunauer–Emmett–Teller (BET) method and the Transmission Electron Microscopy (TEM) studies evidence the influence of the structure-directing agent (ionic surfactant CTAB or non-ionic P123) in the generation of unorganized or well ordered pores in the 92S6 glass. We also demonstrated that when we synthesized glasses with a same composition using the same technique (sol-gel), in presence of surfactants with different carbon chain length, there is a direct correlation between the surfactant and textural properties and structural characteristics. As observed from small-angle XRD patterns and TEM images, synthesis at different temperatures lead to the formation of mesoporous glasses. The properties of these glasses are extremely dependent on the synthesis temperature. We demonstrated also that the bioactivity may be significantly modified by a change on glass textural properties. Finally, the samples were analyzed to quantify the apatite formation ability when soaked in SBF solution. The physico-chemical studies showed apatite-like phases formed at the glasses surface when soaked in SBF. So, our mesoporous glasses are bioactive. These characteristic mesoporous glasses will display good future applications in bone tissue repairing and engineering.

This PhD thesis presents a study of structure-composition correlations of bioactive glasses (BGs) by employing solid-state Nuclear Magnetic Resonance (NMR) spectroscopy. Silicate-based Na2O−CaO−SiO2−P2O5 BGs are utilized clinically and are extensively investigated for bone regeneration purposes. Once implanted in the human body, they facilitate bone regeneration by partially dissolving in the body fluids, followed by the formation of a biomimetic surface-layer of calcium hydroxy-carbonate apatite (HCA). Eventually, the implanted BG totally integrates with the bone. The bioactivity of melt-prepared BGs depends on their composition and structure, primarily on the phosphorus content and the average silicate-network connectivity (NC). We explored these composition-structure relationships for a set of BGs for which the NC and phosphorus contents were varied independently. The short-range structural features of the glasses were explored using 29Si and 31P magic-angle-spinning (MAS) NMR spectroscopy. 31P MAS NMR revealed that the orthophosphate content is directly proportional to the total P content of the glass, with a linear correlation observed between the orthophosphate content and the silicate network connectivity. The bearings of the results for future BG design are discussed. By using multiple-quantum coherence-based 31P NMR experiments, the spatial distribution of orthophosphate groups was probed in the melt prepared BGs, as well as in two mesoporous bioactive glasses prepared by an evaporation-induced self-assembly technique. The results evidence randomly distributed orthophosphate groups in the melt-prepared BGs, whereas the pore-walls of the mesoporous bioactive glasses constitute nanometer-sized clusters of calcium phosphate. The distribution of Na+ ions among the phosphate/silicate groups were studied by heteronuclear dipolar-based 23Na−31P NMR experiments, verifying that sodium is dispersed nearly randomly in the glasses. The phosphorus and proton environments in biomimetically grown HCA were investigated by using 1H and 31P MAS NMR experiments. Our studies revealed that the biomimetic HCA shared many local structural features with synthetic and well-ordered hydroxy-apatite. / <p>At the time of the doctoral defense, the following paper was unpublished and had a status as follows: Paper 4: Accepted.</p>

Orientador: Celso Aparecido Bertran, Italo Odone Mazali / Dissertação (mestrado) - Universidade Estadual de Campinas, Instituto de Quimica / Made available in DSpace on 2018-08-15T20:33:27Z (GMT). No. of bitstreams: 1 Lopes_JoaoHenrique_M.pdf: 3741277 bytes, checksum: 839c748f4fd68d1140366429af1efbc5 (MD5) Previous issue date: 2010 / Mestrado / Físico-Química / Mestre em Química

Les verres bioactifs sont des matériaux particulièrement intéressants en régénération osseuse du fait de leur capacité à stimuler les cellules responsables de la croissance osseuse par les espèces qu’ils relarguent lors de leur dissolution et pour leur capacité à se lier à l’os. Au-delà de leur rôle comme matériau de comblement de défauts osseux, ils pourraient servir de support à la croissance en laboratoire de véritables greffons osseux cultivés à l’aide de seulement quelques cellules d’un patient. Afin d’être efficace, ce support doit posséder une architecture macroporeuse interconnectée pour permettre l’invasion cellulaire ainsi que la vascularisation, nécessaire à la survie des cellules. Ce travail de thèse a pour objectif la réalisation d’un tel support par l’ajout d’une étape de moussage au procédé sol-gel. Ce procédé a été utilisé pour la synthèse de matériaux aux porosités différentes permettant de déterminer une porosité plus prometteuse pour des essais in vivo qui ont montré l’invasion possible de cette mousse par des cellules osseuses. Ce procédé a de plus été rendu plus sûr par la mise au point d’une voie de synthèse alternative dans laquelle l’acide nécessaire au procédé de moussage, mais toxique, a été remplacé avec succès. Cette voie alternative a de plus permis l’organisation de la mésoporosité de la mousse. L’incorporation d’un élément d’intérêt biologique, le strontium, a été réalisé et son influence sur les propriétés et la réactivité du verre a été étudiée. Enfin, une voie de synthèse de nouveaux matériaux composites a été proposée : la grande bioactivité des verres bioactifs est conservée tout en ayant des propriétés mécaniques supérieures grâce à l’utilisation de la gélatine comme phase organique. / Bioactive glasses are very interesting materials for bone regeneration because of their ability to stimulate cells responsible for bone growth with ionic products released during dissolution and for their bone bonding ability. Beyond their role as bone filling materials, they can be used as support for growth of laboratory-made bone grafts cultivated from just a few cells of a patient. This support, named scaffold, has to be an interconnected macroporous architecture in order to allow cell invasion and vascularization which is essential to cell survival. The aim of this thesis work is the realization of such a scaffold using the sol-gel foaming process. This process has been used for the synthesis of materials with different properties that were compared for determination of the most promising for in vivo implantation and was indeed able to allow cell invasion. Moreover, this process was improved to be safer by replacement of hazardous catalyst. This new process also allowed the structuration of the mesoporosity inside the foams. Incorporation of a biologically active element (strontium) was realized and its influence on the glass properties and reactivity was evaluated. Finally, the synthesis of new composite materials has been proposed: the high bioactivity of bioactive glasses is preserved while better mechanical properties are obtained thank to the use of gelatin as organic phase.