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  • Magnesium phosphate cements for endodontic applications with improved long-term sealing ability

     Mestres Bea, Gemma; Aguilera, F. S.; Manzanares, N; Sauro, S; Osorio, R; Toledano, M; Ginebra Molins, Maria Pau
    International endodontic journal
    Date of publication: 2014-02
    Journal article

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    Aim To characterize three radiopaque Magnesium Phosphate Cements (MPCs) developed for endodontic purposes. Methodology Three experimental MPCs containing Bi2O3 were formulated. The experimental cements, which consisted of mixtures of magnesium oxide with different phosphate salts, were characterized for setting time, injectability, porosity, compressive strength and phase composition. The long-term sealing ability of the experimental MPCs applied in single-rooted teeth as root canal filling material or as sealer in combination with gutta-percha was also assessed using a highly sensitive fluid filtration system. A mineral trioxide aggregate (MTA) cement was used as control. Statistical analysis was performed with two- or three-way analysis of variance (anova) and Tukey's test was used for comparisons. Results The addition of 10 wt% Bi2O3 within the composition of the MPCs provided an adequate radiopacity for endodontic applications according to ISO 6876 standard. The reaction products resulting from the MPCs were either struvite (MgNH(4)PO(4)6H(2)O) or an amorphous sodium magnesium phosphate. The porosity of the three MPCs ranged between 4% and 11%. The initial setting time of the experimental cements was between 6 and 9min, attaining high early compressive strength values (17-34 MPa within 2h). All MPC formulations achieved greater sealing ability than MTA (P<0.05) after 3months, which was maintained after 6months for two of the experimental cements (P<0.05). Conclusions These MPCs had adequate handling and mechanical properties and low degradation rates. Furthermore, a stable sealing ability was demonstrated up to 6months when using the cement both as root filling material and as sealer in conjunction with gutta-percha.

  • Biomimetic treatment on dental implants for short-term bone regeneration

     Gil Mur, Francisco Javier; Manzanares, Norberto; Badet de Mena, Armando; Aparicio, Conrado; Ginebra Molins, Maria Pau
    Clinical oral investigations
    Date of publication: 2014-01-01
    Journal article

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    Objectives: The main purpose of this work was to assess the short-term bone regenerative potential of new osteoconductive implants. The novelty of the study lies in the analysis of the effectiveness of a novel two-step treatment which combines shot-blasting with a thermo-chemical treatment, at very short times after implant placement in a minipig model. Materials and methods: Three hundred twenty implants with four different surface treatments, namely bioactivated surfaces, micro-rough grit-blasted, micro-rough acid-etched and smooth as-machined titanium implants were placed into the bone of 20 minipigs. The percent of bone-to-implant contact was determined 3 days, 1, 2, 3 and 10 weeks after implant placement by histomorphometric analysis. Surface composition, topography and wettability of the implant specimens were analysed. Results: The combination of shot-blasting and thermo-chemical treatment accelerated bone regeneration at early stages in comparison with all other treatments between day 3 and week 3 (p < 0.05). The value of osseointegration attained at week 2 was maintained until the end of the experiment without any significant changes (percent direct contact ¿ 85 %). This was mostly attributed to the ability of these implants to form in vivo a layer of apatitic mineral that coated the implant and could rapidly stimulate bone nucleation and growth from the implant surface. Conclusions: The surface quality resulting from this treatment on cpTi provided dental implants with a unique ability of rapid bone regeneration and osseointegration. Clinical relevance: This treatment represents a step forward in the direction of reducing the time prior to implant loading. © 2013 Springer-Verlag Berlin Heidelberg.

  • Biofuncionalización de superficies de titanio con colágeno tipo I para mejorar el sellado biológico de implantes dentales.

     Marín Pareja, Nathalia
    Defense's date: 2014-02-14
    Universitat Politècnica de Catalunya
    Theses

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    Para obtener una regeneración e integración de los tejidos de la encía sobre la superficie de un implante dental, es esencial obtener una respuesta celular apropiada. Para promover una adecuada respuesta celular, la superficie de los materiales ha sido frecuentemente recubierta con un sinnúmero de proteínas, péptidos y otras biomoléculas con propiedades similares a las de las proteínas de la matriz extracelular, las cuales proporcionan sitios de unión celular. Por lo tanto, la estrategia que se propone en este trabajo para promover la integración de los tejidos de la encía sobre el implante es la biofuncionalización de la superficie de titanio con colágeno tipo I, que posee secuencias de aminoácidos GFOGER que promueven la respuesta de fibroblastos y de esta manera se espera una reducción significativamente del tiempo de recuperación de los tejidos post-implantación. Los estudios realizados en este trabajo analizan en profundidad la influencia que tienen tanto el método de activación de la superficie metálica (plasma o ataque acido), como el método de enlace del colágeno (fisisorción o enlace covalente mediante silanos) sobre la cantidad, la estabilidad y la conformación de la capa de colágeno inmovilizada sobre el titanio, y en último término la influencia que éste último tiene sobre la adhesión, proliferación y activación de células fibroblásticas, así como sobre el inicio de la secreción y reorganización de la matriz extracelular.

  • Calcium phosphate cements loaded with basic fibroblast growth factor: Delivery and in vitro cell response

     Perez Antoñanzas, Roman; Kim, Tae-Hyun; Kim, Meeju; Jang, Jun-Hyeog; Ginebra Molins, Maria Pau; Kim, Hae-Won
    Journal of biomedical materials research. Part A
    Date of publication: 2013-04
    Journal article

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    Combining calcium phosphate cements (CPCs) with bioactive molecules improves their bone regeneration potential. Although CPCs are highly osteoconductive, sometimes they have limited biological responses, especially in terms of cell proliferation. Here, we used basic fibroblast growth factor (bFGF) in an -tricalcium phosphate cement with different initial powder sizes (coarse vs. fine; designated as CPC-C and CPC-F, respectively) and investigated the behavior of bFGF loading and release, as well as the effects on osteoblast responses. bFGF was loaded at 10 g/ml or 25 g/ml onto the set form of two types of CPCs, aiming to allow penetration into the pore structure and adsorption onto the cement crystallites. The CPC formulated with fine powder (CPC-F) had higher specific surface area and smaller-sized pores and retained slightly higher amounts of bFGF within the structure. The bFGF release study performed for 3 weeks showed a sustained-release profile; after an initial rapid release over approximately...

    biological responses, especially in terms of cell proliferation. Here, we used basic fibroblast growth factor (bFGF) in an -tricalcium phosphate cement with different initial powder sizes (coarse vs. fine; designated as CPC-C and CPC-F, respectively) and investigated the behavior of bFGF loading and release, as well as the effects on osteoblast responses. bFGF was loaded at 10 g/ml or 25 g/ml onto the set form of two types of CPCs, aiming to allow penetration into the pore structure and adsorption onto the cement crystallites. The CPC formulated with fine powder (CPC-F) had higher specific surface area and smaller-sized pores and retained slightly higher amounts of bFGF within the structure. The bFGF release study performed for 3 weeks showed a sustained-release profile; after an initial rapid release over approximately...

  • Relevance of microstructure for the early antibiotic release of fresh and pre-set calcium phosphate cements

     Canal Barnils, Cristina; Pastorino Carraz, David; Mestres Bea, Gemma; Schuler, Philipp; Ginebra Molins, Maria Pau
    Acta biomaterialia
    Date of publication: 2013
    Journal article

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    Calcium phosphate cements (CPCs) have great potential as carriers for controlled release and vectoring of drugs in the skeletal system. However, a lot of work still has to be done in order to obtain reproducible and predictable release kinetics. A particular aspect that adds complexity to these materials is that they cannot be considered as stable matrices, since their microstructure evolves during the setting reaction. The aims of the present work were to analyze the effect of the microstructural evolution of the CPC during the setting reaction on the release kinetics of the antibiotic doxycycline hyclate and to assess the effect of the antibiotic on the microstructural development of the CPC. The incorporation of the drug in the CPC modified the textural and microstructural properties of the cements by acting as a nucleating agent for the heterogeneous precipitation of hydroxyapatite crystals, but did not affect its antibacterial activity. In vitro release experiments were carried out on readily prepared cements (fresh CPCs), and compared to those of pre-set CPCs. No burst release was found in any formulation. A marked difference in release kinetics was found at the initial stages; the evolving microstructure of fresh CPCs led to a two-step release. Initially, when the carrier was merely a suspension of a-TCP particles in water, a faster release was recorded, which rapidly evolved to a zero-order release. In contrast, pre-set CPCs released doxycycline following non-Fickian diffusion. The final release percentage was related to the total porosity and entrance pore size of each biomaterial.

  • Methods for the preparation of doxycycline-loaded phb micro- and nano-spheres

     Rodriguez Contreras, Alejandra Maria; Canal Barnils, Cristina; Calafell Monfort, Margarita; Ginebra Molins, Maria Pau; Julio Moran, Gemma; Marques Calvo, Maria Soledad
    European polymer journal
    Date of publication: 2013-11
    Journal article

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    Natural and synthetic biodegradable polymers have been investigated for controlled drug release. Poly(3-hydroxybutyrate) can be produced by bacteria and is remarkable for this application due to its excellent biocompatibility and biodegradability. The objective of this work was to study different drug-entrapment and emulsification methods for the obtaining of doxycycline-loaded PHB micro- and nano-spheres. The micro-/nano-particles were prepared by polymer precipitation via dialysis, simple emulsion (O/W) or multiple emulsion (W1/O/W2) applying solvent evaporation in the last two cases. This was carried out either by ultrasonication, dripping and/or high speed stirring. Different processing conditions were varied in order to evaluate their influence on morphology, size, and drug entrapment capabilities. The highest drug loading was obtained by single emulsion with high speed stirring. In the case of multiple emulsion, the combination of ultrasound with high speed stirring resulted in the most elevate process yield and drug loading capability. © 2013 Elsevier Ltd. All rights reserved.

    Natural and synthetic biodegradable polymers have been investigated for controlled drug release. Poly(3-hydroxybutyrate) can be produced by bacteria and is remarkable for this application due to its excellent biocompatibility and biodegradability. The objective of this work was to study different drug-entrapment and emulsification methods for the obtaining of doxycycline-loaded PHB micro- and nano-spheres. The micro-/nano-particles were prepared by polymer precipitation via dialysis, simple emulsion (O/W) or multiple emulsion (W1/O/W2) applying solvent evaporation in the last two cases. This was carried out either by ultrasonication, dripping and/or high speed stirring. Different processing conditions were varied in order to evaluate their influence on morphology, size, and drug entrapment capabilities. The highest drug loading was obtained by single emulsion with high speed stirring. In the case of multiple emulsion, the combination of ultrasound with high speed stirring resulted in the most elevate process yield and drug loading capability.

  • Micro- and nanostructured hydroxyapatitecollagen microcarriers for bone tissue-engineering applications

     Perez, R.A.; Altankov, George Petrov; Jorge Herrero, E.; Ginebra Molins, Maria Pau
    Journal of tissue engineering and regenerative medicine
    Date of publication: 2013-05
    Journal article

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    Novel hydroxyapatite (HA)collagen microcarriers (MCs) with different micro/nanostructures were developed for bone tissue-engineering applications. The MCs were fabricated via calcium phosphate cement (CPC) emulsion in oil. Collagen incorporation in the liquid phase of the CPC resulted in higher MC sphericity. The MCs consisted of a porous network of entangled hydroxyapatite crystals, formed as a result of the CPC setting reaction. The addition of collagen to the MCs, even in an amount as small as 0.8wt%, resulted in an improved interaction with osteoblast-like Saos-2 cells. The micro/nanostructure and the surface texture of the MCs were further tailored by modifying the initial particle size of the CPC. A synergistic effect between the presence of collagen and the nanosized HA crystals was found, resulting in significantly enhanced alkaline phosphatase activity on the collagen-containing nanosized HA MCs.

  • Antimicrobial properties and dentin bonding strength of magnesium phosphate cements

     Mestres Bea, Gemma; Abdolhosseini, Masha; Bowles, Walter; Huang, S.H.; Aparicio, Conrado; Gorr, Sven Ulrik; Ginebra Molins, Maria Pau
    Acta biomaterialia
    Date of publication: 2013-09
    Journal article

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    The main objective of this work was to assess the antimicrobial properties and the dentin-bonding strength of novel magnesium phosphate cements (MPC). Three formulations of MPC, consisting of magnesium oxide and a phosphate salt, NH4H2PO4, NaH2PO4 or a mixture of both, were evaluated. As a result of the setting reaction, MPC transformed into either struvite (MgNH4PO4·6H 2O) when NH4H2PO4 was used or an amorphous magnesium sodium phosphate when NaH2PO4 was used. The MPC had appropriate setting times for hard tissue applications, high early compressive strengths and higher strength of bonding to dentin than commercial mineral trioxide aggregate cement. Bacteriological studies were performed with fresh and aged cements against three bacterial strains, Escherichia coli, Pseudomonas aeruginosa (planktonic and in biofilm) and Aggregatibacter actinomycetemcomitans. These bacteria have been associated with infected implants, as well as other frequent hard tissue related infections. Extracts of different compositions of MPC had bactericidal or bacteriostatic properties against the three bacterial strains tested. This was associated mainly with a synergistic effect between the high osmolarity and alkaline pH of the MPC. These intrinsic antimicrobial properties make MPC preferential candidates for applications in dentistry, such as root fillers, pulp capping agents and cavity liners.

  • Fibrinogen nanofibers for guiding endothelial cell behavior

     Gugutkov, Dencho; Gustavsson, Johan; Ginebra Molins, Maria Pau; Altankov, George Petrov
    Biomaterials science
    Date of publication: 2013-01-01
    Journal article

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    This paper describes the biological consequences of presenting electrospun fibrinogen (FBG) to endothelial cells as a spatially organized nanofibrous matrix. Aligned and randomly oriented FBG nanofibers with an average diameter of less than 200 nm were obtained by electrospinning of native FBG solution. Electrophoretic profiling confirmed that the electrospun FBG resembled the native protein structure, and fluorescent tracing of FITC-labeled FBG showed that electrospun fibers withstood immersion in physiological solutions reasonably well for several days. With respect to cellular interactions, the nanofibrous FBG matrix provided better conditions for initial recognition by human umbilical vein endothelial cells compared to pre-adsorbed FBG on a flat surface. Furthermore, the spatial organization of electrospun FBG fibers presented opportunities for guiding the cellular behavior in a way that is not possible when the protein is presented in another form (e. g. adsorbed or soluble). For example, on aligned FBG fibers, cells rapidly oriented themselves along the fibers, and time-lapse recordings revealed pronounced cellular movements restricted to the fiber direction. In great contrast, on randomly deposited fibers, cells acquired a stellate-like morphology and became locally immobilized by the fibers. We also show that the FBG fiber orientation significantly influenced both the cytoskeleton organization in confluent cell layers and the orientation of the extracellular fibronectin matrix secreted by the cells. In conclusion, this study demonstrates that electrospun FBG nanofibers can be a promising tool for guiding endothelial cell behavior for tissue engineering applications.

  • Injectable collagen/alpha-tricalcium phosphate cement: collagen-mineral phase interactions and cell response

     Perez Antoñanzas, Roman; Ginebra Molins, Maria Pau
    Journal of materials science. Materials in medicine
    Date of publication: 2013-02
    Journal article

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    A bone inspired material was obtained by incorporating collagen in the liquid phase of an alpha-tricalcium phosphate cement, either in solubilized or in fibrilized form. This material was able to set in situ, giving rise to a calcium deficient hydroxyapatite (CDHA)/collagen composite. The morphology and distribution of collagen in the composite was shown to be strongly affected by the collagen pre-treatment. The interactions between collagen and the inorganic phase were assessed by FTIR. A red shift of the amide I band was indicative of calcium chelation by the collagen carbonyl groups. The rate of CDHA formation was not affected when diluted collagen solutions (1 mg/ml) were used, whereas injectability improved. The presence of solubilized collagen, even in low amount (1 %), increased cell adhesion and proliferation on the composites. Still in the absence of osteogenic medium, significant ALP activity was detected both in the inorganic and the collagen-containing cements.

  • FOSFATOS DE CALCIO BIOMIMETICOS: MODULANDO LA POROSIDAD DE NANO A MACROESCALA PARA

     Ginebra Molins, Maria Pau
    Participation in a competitive project

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  • Osteoblast-like cellular response to dynamic changes in the ionic extracellular environment produced by calcium-deficient hydroxyapatite

     Gustavsson, Johan; Ginebra Molins, Maria Pau; Planell Estany, Josep Antón; Engel Lopez, Elisabet
    Journal of materials science. Materials in medicine
    Date of publication: 2012-10
    Journal article

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  • Silicon-stabilized alpha-tricalcium phosphate and its use in a calcium phosphate cement: characterization and cell response

     Mestres Beà, Gemma; Le Van, Clemence; Ginebra Molins, Maria Pau
    Acta biomaterialia
    Date of publication: 2012-01-31
    Journal article

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  • Assessment of protein entrapment in hydroxyapatite scaffolds by size exclusion chromatography

     Español Pons, Montserrat; Casals, Isidre; Lamtahri, Sarah; Valderas, Maite; Ginebra Molins, Maria Pau
    Biointerphases: an open access journal for the biomaterials interface community
    Date of publication: 2012-12
    Journal article

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  • Calcium phosphate cements as drug delivery materials

     Ginebra Molins, Maria Pau; Canal Barnils, Cristina; Español Pons, Montserrat; Pastorino, David; Montufar Jimenez, Edgar Benjamin
    Advanced drug delivery reviews
    Date of publication: 2012-01-25
    Journal article

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    Calcium phosphate cements are used as synthetic bone grafts, with several advantages, such as their osteoconductivity and injectability. Moreover, their low-temperature setting reaction and intrinsic porosity allow for the incorporation of drugs and active principles in the material. It is the aim of the present work to: a) provide an overview of the different approaches taken in the application of calcium phosphate cements for drug delivery in the skeletal system, and b) identify the most significant achievements. The drugs or active principles associated to calcium phosphate cements are classified in three groups, i) low molecular weight drugs; ii) high molecular weight biomolecules; and iii) ions.

  • Ceramics

     Español Pons, Montserrat; Perez Antoñanzas, Roman; Montufar Jimenez, Edgar Benjamin; Ginebra Molins, Maria Pau
    Date of publication: 2012-04-10
    Book chapter

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  • Dynamic behavior of type IV collagen at cell-biomaterial interface

     Miranda Guerra coelho, Nuno
    Defense's date: 2012-05-25
    Department of Automatic Control, Universitat Politècnica de Catalunya
    Theses

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  • Novel phosphate-based cements for clinical applications  Open access

     Mestres Bea, Gemma
    Defense's date: 2012-07-09
    Department of Materials Science and Metallurgy, Universitat Politècnica de Catalunya
    Theses

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    This Thesis aims at the development of two novel families of inorganic phosphate cements with suitable characteristics for clinical applications in hard tissue regeneration or replacement. It is organized in two distinct parts. The first part focuses at the development of silicon-doped a-tricalcium phosphate and the subsequent preparation of a silicon-doped calcium phosphate cement for bone regeneration applications. For this purpose, silicon-doped a-tricalcium phosphate was synthesized by sintering a calcium-deficient hydroxyapatite at 1250ºC with different amounts of silicon oxide. The high temperature polymorph a-tricalcium phosphate was stabilized by the presence of silicon, which inhibited reversion of the b-a transformation, whereas in the Si-free a-tricalcium phosphate completely reverted to the b-polymorph. It was observed that the presence of Si did not alter the b-a transformation temperature. Both the Si-doped a-tricalcium phosphate and its Si-free counterpart were used as reactants in the formulation of calcium phosphate cements. While Si-doped a-tricalcium phosphate showed faster hydrolysis to calcium deficient hydroxyapatite, the composition, morphology and mechanical properties of both cements were similar upon completion of the reaction. When the samples were immersed in simulated body fluid, the Si-doped cement exhibited a faster deposition of an apatite layer on its surface than its Si-free counterpart, suggesting an enhanced bioactivity of the doped-cement. An in vitro cell culture study, in which osteoblast-like cells were exposed to a medium modified by the materials, showed a delay in cell proliferation and a stimulation of cell differentiation, the differentiation being more marked for the Si-containing cement. These results were attributed to the Ca depletion from the medium by both cements and to the continuous Si release detected for the Si-containing cement. The second part of this Thesis is focused on the development of a new family of inorganic phosphate-based cements for biomedical applications, namely magnesium phosphate cements. The magnesium phosphate cements have been extensively used in civil engineering due to their fast setting, early strength acquisition and adhesive properties, properties that can be also of use for biomedical applications. However, there are some aspects that should be improved before they can be used in the human body, namely their high exothermic setting reaction and the release of potentially harmful ammonium ions. Therefore, a new family of magnesium phosphate cements was explored as candidate biomaterials for hard tissue applications. These cements were prepared by mixing magnesium oxide with either sodium dihydrogen phosphate, ammonium dihydrogen phosphate or an equimolar mixture of both. The exothermia and the setting kinetics of the new cement formulations were tailored. The ammonium-containing magnesium phosphate cements resulted in struvite as the major reaction product, whereas the magnesium phosphate cement prepared with sodium dihydrogen phosphate resulted in an amorphous product. The magnesium phosphate cements studied showed an early compressive strength substantially higher than that of conventional apatitic calcium phosphate cements. Moreover, they showed antimicrobial properties against bacteria present in dental infections, which were attributed to the synergistic effect of a high osmolarity and high pH of the cement extracts. These properties make magnesium phosphate cements good candidates for endodontic applications. It is with this latter point in mind that some of the most relevant physico-chemical properties were further optimized and characterized. Particularly, their radiopacity was enhanced by the addition of bismuth oxide. The sealing efficiency of the magnesium phosphate cements and their adhesion to dentin were shown to be comparable or even higher than those presented by other inorganic cements used for endodontic treatments.

    Aquesta Tesi té com a objectiu el desenvolupament de dues noves famílies de ciments inorgànics de base fosfat amb propietats adequades per a aplicacions clíniques en regeneració o substitució de teixits durs. La Tesi està organitzada en dues parts. La primera part està centrada en el desenvolupament de fosfat tricàlcic a dopat amb silici i la subseqüent preparació de ciments de fosfat de calci dopats amb silici. Per a aquest objectiu, es va obtenir fosfat tricàlcic a dopat amb silici mitjançant la sinterització d’una hidroxiapatita deficient en calci amb diferents quantitats d’òxid de silici a 1250°C. La presència de silici va estabilitzar el polimorf d’alta temperatura (fosfat tricàlcic a), inhibint-se la reversió de la transformació b-a, mentre que el fosfat tricàlcic a sense silici va revertir completament a polimorf b. La presència de silici no va alterar la temperatura de la transformació b-a. Tant el fosfat tricàlcic a dopat amb silici com el seu homòleg sense silici van ser utilitzats com a reactius en la formulació de ciments de fosfat de calci. Si bé el fosfat tricàlcic a dopat amb silici va mostrar en les fases inicials una hidròlisi més ràpida a hidroxiapatita deficient en calci, un cop completada la reacció, la composició, morfologia i propietats mecàniques d’ambdós ciments van ser similars. L’estudi de bioactivitat mitjançant la immersió de les mostres en fluid corporal simulat va donar com a resultat la formació d’una capa d’apatita a la superfície del ciment dopat amb silici, més ràpida que al seu homòleg sense silici, fet que va suggerir una bioactivitat millorada del ciment dopat. L’estudi in vitro, en el qual cèl·lules osteoblàstiques es van exposar a un medi de cultiu que havia estat prèviament en contacte amb els ciments estudiats, va mostrar un retràs en la proliferació cel·lular i un estímul de la diferenciació cel·lular, aquest últim més marcat pel ciment que contenia silici. Aquests resultats es van atribuir a la reducció de calci en els medis en els quals estaven introduïts els ciments i a l’alliberament continu d’ions silici per part del ciment que en contenia.

  • Medalla Narcís Monturiol al mèrit científic i tecnològic

     Ginebra Molins, Maria Pau
    Award or recognition

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  • Premi ICREA Acadèmia

     Pastor Satorras, Romualdo; Ginebra Molins, Maria Pau; Arroyo Balaguer, Marino; Camps Carmona, Adriano Jose; Aleman Llanso, Carlos Enrique
    Award or recognition

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  • Variation of the superelastic properties and nickel release from original and reused NiTi orthodontic archwires

     Gil Mur, Francisco Javier; Espinar, E.; Llamas, J.M.; Manero Planella, Jose M.; Ginebra Molins, Maria Pau
    Journal of the mechanical behavior of biomedical materials
    Date of publication: 2012
    Journal article

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    Reuse of NiTi orthodontic wires has become increasingly common in dental clinics. For sterilization and recovery of the original superelastic properties of the wires, a heat treatment is usually performed between 500 and 600 ◦C. The aim of this study was to analyze the effect of these thermal treatments on the mechanical behavior and the microstructure of NiTi archwires of different compositions. A reduction of the Ni content was observed in the matrix of the thermally treated archwires, due to the formation of Ti3Ni4 precipitates. The nickel-rich precipitates were observed and characterized by Transmission Electron Microscopy (TEM) and electron diffraction. They were found to alter the mechanical properties of the wires, decreasing the transformation stresses, and causing a loss of activation of the NiTi archwires. The release of nickel was higher in the original archwires than in the reused ones, due to the matrix nickel depletion caused by the precipitation of Ti3Ni4.

  • Injectable calcium-phosphate-based composites for skeletal bone treatments

     Ambrosio, Luigi; Guarino, V.; Torricelli, P.; Fini, M.; Ginebra Molins, Maria Pau; Planell Estany, Josep Antón; Giardino, R.
    Biomedical materials
    Date of publication: 2012
    Journal article

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  • Hydroxyapatite foams with tuned macro- and microstructure

     Español Pons, Montserrat; Valderas, Maite; Ginebra Molins, Maria Pau
    Symposium and Annual Meeting of International Society for Ceramics in Medicine
    Presentation's date: 2011-11-10
    Presentation of work at congresses

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  • The relevance of the setting reaction on the injectability of tricalcium phosphate pastes

     Montufar Jimenez, Edgar Benjamin; Fernandez, Francesc; Maazouz, Yassine; Ginebra Molins, Maria Pau
    Symposium and Annual Meeting of International Society for Ceramics in Medicine
    Presentation's date: 2011-11-07
    Presentation of work at congresses

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  • Dry mechanosynthesis of nanocrystalline calcium deficient hydroxyapatite: Structural characterisation

     Mochales Palau, Carolina; Wilson, R. M.; Dowker, S.E.P.; Ginebra Molins, Maria Pau
    Journal of alloys and compounds
    Date of publication: 2011-07-07
    Journal article

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    Dry mechanosynthesis is an efficient technique to synthesise nanocrystalline calcium deficient hydroxyapatites (CDHA). The mechanisms underlying a mechanochemical reaction are different from those triggering a dissolution mediated process, and this can have an effect on the structural features of the product. In this work, a nanocrystalline CDHA with Ca/P molar ratio of 1.5 obtained by means of dry mechanosynthesis of calcium oxide and dicalcium phosphate dihydrate was analysed. Spectroscopic techniques confirmed the presence of hydrogen phosphate (HPO4 2−) groups and a non-apatitic environment of the phosphate ions and disordered hydroxyl groups due to the nanometric size of the crystals. Lattice parameters of mechanosynthesised CDHA showed a small increase in the a lattice parameter (9.4418(20)A˚ ) and a small decrease in the c lattice parameter (6.8745(17)A˚ ), in agreement with the values reported in the literature for precipitated CDHAs. A prolonged milling resulted in an increase of the crystallinity of the CDHA and its partial decomposition into -TCP by the loss of OH− and HPO4 2− groups.

  • Ion reactivity of calcium-deficient hydroxyapatite in standard cell culture media

     Gustavsson, Johan Mikael; Ginebra Molins, Maria Pau; Engel Lopez, Elisabet; Planell Estany, Josep Antón
    Acta biomaterialia
    Date of publication: 2011-12
    Journal article

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  • Fluoride-containing nanoporous calcium-silicate MTA cements for endodontics and oral surgery: Early fluorapatite formation in a phosphate-containing solution

     Gandolfi, M.G.; Taddei, P.; Siboni, F.; Modena, E.; Ginebra Molins, Maria Pau; PRATI, CLAUDIO
    International endodontic journal
    Date of publication: 2011-10
    Journal article

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    Gandolfi MG, Taddei P, Siboni F, Modena E, Ginebra MP, Prati C. Fluoride-containing nanoporous calcium-silicate MTA cements for endodontics and oral surgery: early fluorapatite formation in a phosphate-containing solution. International Endodontic Journal, 44, 938–949, 2011. Aim To test the chemical–physical properties and apatite-forming ability of experimental fluoride-doped calcium silicate cements designed to create novel bioactive materials for use in endodontics and oral surgery. Methodology A thermally treated calcium silicate cement (wTC) containing CaCl2 5%wt was modified by adding NaF 1%wt (FTC) or 10%wt (F10TC). Cements were analysed by environmental scanning electron microscopy with energy-dispersive X-ray analysis, IR and micro-Raman spectroscopy in wet conditions immediately after preparation or after ageing in a phosphate-containing solution (Dulbecco’s phosphatebuffered saline). Calcium and fluoride release and pH of the storage solution were measured. The results obtained were analysed statistically (Tukey’s HSD test and two-way anova). Results The formation of calcium phosphate precipitates (spherulites) was observed on the surface of 24 h-aged cements and the formation of a thick bone-like B-type carbonated apatite layer (biocoating) on 28 day-aged cements. The rate of apatite formation was FTC > F10TC > wTC. Fluorapatite was detected on FTC and F10TC after 1 day of ageing, with a higher fluoride content on F10TC. All the cements released calcium ions. At 5 and 24 h, the wTC had the significantly highest calcium release (P < 0.001) that decreased significantly over the storage time. At 3–28 days, FTC and F10TC had significantly higher calcium release than wTC (P < 0.05). The F10TC had the significantly highest fluoride release at all times (P < 0.01) that decreased significantly over storage time. No significant differences were observed between FTC and wTC. All the cements had a strong alkalinizing activity (OH) release) that remained after 28 days of storage. Conclusions The addition of sodium fluoride accelerated apatite formation on calcium silicate cements. Fluoride-doped calcium silicate cements had higher bioactivity and earlier formation of fluorapatite. Sodium fluoride may be introduced in the formulation of mineral trioxide aggregate cements to enhance their biological behaviour. F-doped calcium silicate cements are promising bone cements for clinical endodontic use.

  • Regeneración ósea

     Ginebra Molins, Maria Pau
    Investigación y ciencia
    Date of publication: 2011-07
    Journal article

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  • New processing and applications of collagen containing calcium phosphate cements  Open access  awarded activity

     Pérez Antoñanzas, Román
    Defense's date: 2011-07-22
    Universitat Politècnica de Catalunya
    Theses

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    When bone regeneration is needed, natural bone grafts are widely used. They are the best option since they present the same composition to that of bone, contain living cells with osteogenic potential, growth factors that induce cell differentiation into osteoblasts and extracellular matrix proteins that facilitate bone healing. However, this system presents some drawbacks, such as pain, morbidity, possible transmission of diseases in some cases, as well as limited availability. That is why synthetic bone grafts are one of the main objectives of the research in regenerative medicine and tissue engineering. This new discipline is based on the development of new biomaterials and on the comprehension of the interactions between the cells and the material in order to enhance the bone healing response. The present thesis is focused on calcium phosphate cements-based materials. CPC have the ability to transform an injectable paste made of calcium phosphates, into a phase similar to that of bone, hydroxyapatite. The CPC are well known for their osteoconductive properties. Nevertheless, these may be improved from a biological point of view and can be further processed to obtain materials with new morphologies and different applications. Therefore, the incorporation of collagen in these CPC was though as a way to enhance their biological performance. Furthermore, new processing approaches were studied, as well as their applications in new fields. The thesis is divided in three main parts: i) injectable composite cements; ii) composite macroporous scaffolds for tissue engineering and iii) composite microcarriers. In the first part, the fabrication of injectable composite cements is described as well their physico-chemical and morphological features. It is observed that the setting reaction is delayed in the presence of collagen during the initial minutes of reaction. Already after 1 hour the kinetics are similar in the presence and absence of collagen, without affecting the final product of reaction. The presence of collagen increases the injectability of the cements, whereas the mechanical properties decrease as the collagen concentration increases. From a biological point of view, the addition of collagen results in an increase in the initial cell adhesion as well as an increase in the cell proliferation rates. In the second part, macroporous scaffolds made of collagen and CPC are fabricated. These scaffolds are prepared through the freeze-drying of a collagen-CPC slurry. Different amounts of CPC are incorporated in the scaffolds. When mesenchymal stem cells are cultured on these scaffolds, it is observed that as the CPC content increases in the scaffolds, the cell differentiation increases, whereas the proliferation decreases. Further improvement of the scaffolds can be achieved though the incorporation of a BMP-7 gene into the scaffolds, in order to stimulate their osteoinductivity. The results show that as the gene incorporated in the scaffolds increases, there is an increase in the BMP-7 production, although this increase is associated with an increase in cell proliferation. In the third and final part, spherical microcarriers containing either gelatin or collagen are produced through the setting reaction of the CPC in a water in oil emulsion. The emulsion and CPC compositions can be adjusted in order to control the final features of the microcarriers. The in vitro characterization of the microcarriers reveals that under static and dynamic culturing conditions, microcarrieres are able to support cell attachment, proliferation and differentiation.

    Cuando la regeneración ósea es necesaria, los injertos de hueso natural son ampliamente utilizados. Son la mejor opción debido a que presentan la misma composición que el hueso, contienen células vivas con potencial osteogénico, factores de crecimiento que inducen la diferenciación de las células a osteoblastos y proteínas de la matriz extracelular que facilitan la regeneración ósea. A pesar de esto, este sistema presenta algunos inconvenientes, tales como el dolor, morbidez, posible transmisión de enfermedades en algunos casos, al igual que una disponibilidad limitada. Por ello, los injertos de hueso sintético son uno de los principales objetivos de la investigación en medicina regenerativa e ingeniería de tejidos. Esta nueva disciplina se basa en el desarrollo de nuevos biomateriales y en la comprensión de las interacciones entre las células y los materiales con el fin de incrementar la regeneración ósea. La presente tesis se centra en materiales basados en los cementos de fosfato de calcio (CPC). Los CPC tienen la habilidad de transformar una pasta inyectable formada por fosfatos de calcio, en una fase similar a la del hueso, que es la hidroxiapatita. Los CPC son bien conocidos por sus propiedades de osteoconductividad. Sin embargo, estos se pueden mejorar des de un punto de vista biológico y pueden ser procesados con el fin de obtener nuevos materiales con nuevas morfologías y aplicaciones. Por ello, la incorporación de colágeno en estos CPC fue pensada como una manera de incrementar el comportamiento biológico. Se estudiaron nuevas rutas de procesado, al igual que sus aplicaciones. La tesis está dividida en tres partes: i) cementos compuesto inyectables; ii) andamios compuestos macroporosos para ingeniera de tejidos y iii) microtransportadores compuestos. En la primera parte, se describe la fabricación del cemento de fosfato de calcio compuesto y la caracterización físico-química y morfológica del material. Se observa que la reacción de fraguado se retrasa en presencia del colágeno durante los minutos iniciales de reacción. Sin embargo, después de solamente una hora, se observa como la presencia de colágeno no afecta a la cinética de reacción ni al producto final de reacción. La presencia del colágeno incrementa la inyectabilidad de los cementos, mientras que las propiedades mecánicas bajan al incrementar la concentración de colágeno. Desde un punto de vista biológico, la incorporación de colágeno resulta en un incremento de la adhesión celular inicial y un incremento de la proliferación celular. En la segunda parte, se fabrican andamios macroporosos de colágeno con CPC. Estos andamios se preparan a través de la liofilización de mezclas de colágeno y CPC. Se incorporan diversas cantidades de CPC en los andamios. Cuando se cultivan células mesenquimales en los andamios, se ve que a medida que se incrementa la cantidad de CPC en el andamio, la diferenciación celular se incrementa, mientras que la proliferación disminuye. Los andamios se pueden mejorar mediante la incorporación de un gen para expresar la proteína BMP-7 con el fin de incrementar la osteoinducción. Los resultados muestran que al aumentar la cantidad de gen incorporado en el andamio, se incrementa la producción de BMP-7, aunque este incremento va asociado con un incremento en la proliferación celular. En la tercera y última parte, se fabrican microtransportadores esféricos que contienen gelatina o colágeno mediante la reacción de fraguado del CPC en una emulsión de agua en aceite. La emulsión y la composición del CPC se pueden ajustar con el fin de controlar las propiedades finales de los microtransportadores. La caracterización in vitro de los microtransportadores revela que bajo condiciones de cultivo estáticas y dinámicas, los microntransportadores son capaces de soportar adhesión celular, proliferación y diferenciación.

  • Desarrollo y Caracterización de Andamios Biodegradables para Sustitución Ósea mediante Ingeniería Tisular

     Márquez Pérez, Lucia
    Defense's date: 2011-11-29
    Department of Automatic Control, Universitat Politècnica de Catalunya
    Theses

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  • Desarrollo de un cemento de fosfato de calcio macroporoso: influencia de la macroporosidad y de la microestructura en el comportamiento biológico  Open access

     Del Valle Fresno, Sergio
    Defense's date: 2011-05-27
    Department of Materials Science and Metallurgy, Universitat Politècnica de Catalunya
    Theses

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    Los cementos de fosfato de calcio son biomateriales utilizados para la regeneración ósea. En esta tesis doctoral se estudia la influencia de la microestructura y la macroporosidad en el comportamiento biológico de un cemento de fosfato de calcio. En la primera parte, se caracterizaron las propiedades físico-químicas y superficiales de dos sustratos de apatita deficiente en calcio con diferente microestructura obtenidos a partir de un cemento de fosfato de calcio (CPC) cuyo principalmente componente es el fosfato tricálcico en fase $\alpha$. % con dos distribuciones de tamaño de partícula distintos. Se estudió la influencia de la microestructura en el comportamiento celular y la adsorción de proteínas como la albúmina, la fibronectina y la lisozima. El uso de dos agentes desorción (EDTA y SDS) permitió evidenciar la influencia de la morfología y tamaño de los cristales de apatita en la fuerza de adhesión de las proteínas estudiadas. Los cultivos celulares con la línea MG-63 mostraron el efecto de la microestructura y el intercambio iónico sobre la proliferación celular. Se observó asimismo una estimulación en la diferenciación celular en uno de los sustratos que fue atribuido a un efecto de la topografía. En la segunda parte, se desarrolló un cemento macroporoso inyectable para aplicaciones médicas, utilizando como agente espumante una solución proteica de albumen. Se optimizó la obtención de la macroporosidad a partir de variables como: la distribución del tamaño de partícula, la relación entre la fase sólida y la fase líquida, la cantidad de agente espumante y la adición de un agente de cohesión como el alginato de sodio para posibilitar su inyección directa en el lugar de implantación. Por último, se demostró mediante estudios \emph{in vivo} en fémur de conejos un mayor potencial de regeneración ósea por parte del cemento macroporoso en comparación con su homólogo microporoso, al obtenerse una mayor cantidad de tejido óseo y una mayor reabsorción en el cemento macroporoso.

  • Espumas inyectables de hidroxiapatita para regeneración ósea

     Montufar Jimenez, Edgar Benjamin; Ginebra Molins, Maria Pau
    Date of publication: 2011-10-08
    Book

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  • Preparación de una propuesta para la convocatoria NMP-2010-LARGE-4 del FP7

     Rodriguez Rius, Daniel; Canal Barnils, Cristina; Español Pons, Montserrat; Manero Planella, Jose M.; Gil Mur, Francisco Javier; Pegueroles Neyra, Marta; Ginebra Molins, Maria Pau
    Participation in a competitive project

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  • NOVEL BIOMIMETIC STRATEGY FOR BONE REGENERATION

     Canal Barnils, Cristina; Gil Mur, Francisco Javier; Manero Planella, Jose M.; Español Pons, Montserrat; Ginebra Molins, Maria Pau
    Participation in a competitive project

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  • Mechanical behaviour of synthetic surgical meshes: Finite element simulation of the herniated abdominal wall

     Hernández Gascón, B.; Peña, Estefania; Melero, H.; Pascual, Gemma; Doblaré, Manuel; Ginebra Molins, Maria Pau; Bellón, J.M.; Calvo, Belén
    Acta biomaterialia
    Date of publication: 2011-11
    Journal article

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  • Porous hydroxyapatite and gelatin/hydroxyapatite microspheres obtained by calcium phosphate cement emulsion

     Perez Antoñanzas, Roman; Del Valle, Sergio; Altankov, George Petrov; Ginebra Molins, Maria Pau
    Journal of biomedical materials research. Part B, Applied biomaterials
    Date of publication: 2011-03
    Journal article

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  • Comparison of a low molecular weight and a macromolecular surfactant as foaming agents for injectable self setting hydroxyapatite foams: Polysorbate 80 versus gelatine

     Montufar Jimenez, Edgar Benjamin; Traykova, Tania; Planell Estany, Josep Antón; Ginebra Molins, Maria Pau
    Materials science and engineering C. Biomimetic and supramolecular systems
    Date of publication: 2011-10-10
    Journal article

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    Hydroxyapatite foams are potential synthetic bone grafting materials or scaffolds for bone tissue engineering. A novel method to obtain injectable hydroxyapatite foams consists in foaming the liquid phase of a calcium phosphate cement. In this process, the cement powder is incorporated into a liquid foam, which acts as a template for macroporosity. After setting, the cement hardens maintaining the macroporous structure of the foam. In this study a low molecular weight surfactant, Polysorbate 80, and a protein, gelatine, were compared as foaming agents of a calcium phosphate cement. The foamability of Polysorbate 80 was greater than that of gelatine, resulting in higher macroporosity in the set hydroxyapatite foam and higher macropore interconnectivity. Gelatine produced less interconnected foams, especially at high concentrations, due to a higher liquid foam stability. However it increased the injectability and cohesion of the foamed paste, and enhanced osteoblastic-like cell adhesion, all of them important properties for bone grafting materials.

  • Fibre-reinforced calcium phosphate cements: a review

     Canal Barnils, Cristina; Ginebra Molins, Maria Pau
    Journal of the mechanical behavior of biomedical materials
    Date of publication: 2011
    Journal article

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    Calcium phosphate cements (CPC) consist of one or more calcium orthophosphate powders, which upon mixing with water or an aqueous solution, form a paste that is able to set and harden after being implanted within the body. Different issues remain still to be improved in CPC, such as their mechanical properties to more closely mimic those of natural bone, or their macroporosity to favour osteointegration of the artificial grafts. To this end, blends of CPC with polymer and ceramic fibres in different forms have been investigated. The present work aims at providing an overview of the different approaches taken and identifying the most significant achievements in the field of fibre-reinforced calcium phosphate cements for clinical applications, with special focus on their mechanical properties.

  • Electrochemical microelectrodes for improved spatial and temporal characterization of aqueous environments around calcium phosphate cements.

     Gustavsson, Johan Mikael; Ginebra Molins, Maria Pau; Planell Estany, Josep Antón; Engel Lopez, Elisabet
    Acta biomaterialia
    Date of publication: 2011-10-07
    Journal article

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    Calcium phosphate compounds can potentially influence cellular fate through ionic substitutions. However, to be able to turn such solution-mediated processes into successful directors of cellular response, a perfect understanding of the material-induced chemical reactions in situ is required. We therefore report on the application of home-made electrochemical microelectrodes, tested as pH and chloride sensors, for precise spatial and temporal characterization of different aqueous environments around calcium phosphate- based biomaterials prepared from a-tricalcium phosphate using clinically relevant liquid to powder ratios. The small size of the electrodes allowed for online measurements in traditionally inaccessible in vitro environments, such as the immediate material–liquid interface and the interior of curing bone cement. The kinetic data obtained has been compared to theoretical sorption models, confirming that the proposed setup can provide key information for improved understanding of the biochemical environment imposed by chemically reactive biomaterials.

  • Novel magnesium phosphate cements with high early strength and antibacterial properties

     Mestres, Gemma; Ginebra Molins, Maria Pau
    Acta biomaterialia
    Date of publication: 2011-04
    Journal article

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    Magnesium phosphate cements (MPCs) have been extensively used as fast setting repair cements in civil engineering. They have properties that are also relevant to biomedical applications, such as fast setting, early strength acquisition and adhesive properties. However, there are some aspects that should be improved before they can be used in the human body, namely their highly exothermic setting reaction and the release of potentially harmful ammonia or ammonium ions. In this paper a new family of MPCs was explored as candidate biomaterials for hard tissue applications. The cements were prepared by mixing magnesium oxide (MgO) with either sodium dihydrogen phosphate (NaH2PO4) or ammonium dihydrogen phosphate (NH4H2PO4), or an equimolar mixture of both. The exothermia and setting kinetics of the new cement formulations were tailored to comply with clinical requirements by adjusting the granularity of the phosphate salt and by using sodium borate as a retardant. The ammonium-containing MPC resulted in struvite (MgNH4PO4 6H2O) as the major reaction product, whereas the MPC prepared with sodium dihydrogen phosphate resulted in an amorphous product. Unreacted magnesium oxide was found in all the formulations. The MPCs studied showed early compressive strengths substantially higher than that of apatitic calcium phosphate cements. The Na-containing MPCs were shown to have antibacterial activity against Streptococcus sanguinis, which was attributed to the alkaline pH developed during the setting reaction.

  • Cell response to collagen-calcium phosphate cement scaffolds investigated for nonviral gene delivery

     Pérez, Ricardo A.; Ginebra Molins, Maria Pau; Spector, M.
    Journal of materials science. Materials in medicine
    Date of publication: 2011-04
    Journal article

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    Collagen-hydroxyapatite (HA) scaffolds for the non-viral delivery of a plasmid encoding the osteoinductive protein bone morphogenetic protein (BMP)-7 were developed. The collagen-HA was obtained by the combination of calcium phosphate cement in a collagen template. The effect on cell behavior of increasing amounts of HA in the scaffolds was evaluated. Collagen-HA scaffolds containing 13, 23 or 83 wt% HA were prepared. Cell proliferation was reduced in the 83% HA scaffold after 1 day compared to 13 and 23% HA, but by 14 days the number of cells in 83% HA considerably increased. Alkaline phosphatase (ALP) activity was 8 times higher for the 83% HA scaffolds. BMP-7 plasmid was incorporated into the 83% HA scaffold. The transfection was low, although significant levels of BMP7 were expressed, associated with an increase in cell proliferation.

  • Reduction of Ni release and improvement of the friction behaviour of NiTi orthodontic archwires by oxidation treatments

     Espinar Escalona, Eduardo; Llamas, Jose Maria; Michiardi, Alexandra; Ginebra Molins, Maria Pau; Gil Mur, Francisco Javier
    Journal of materials science. Materials in medicine
    Date of publication: 2011-03-25
    Journal article

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    This work studies NiTi orthodontic archwires that have been treated using a new oxidation treatment for obtaining Ni-free surfaces. The titanium oxide on the surface significantly improves corrosion resistance and decreases nickel ion release, while barely affecting transformation temperatures. This oxidation treatment avoids the allergic reactions or toxicity in the surrounding tissues produced by the chemical degradation of the NiTi. In the other hand, the lack of low friction coefficient for the NiTi superelastic archwires makes difficult the optimal use of these materials in Orthodontic applications. In this study, the decrease of this friction coefficient has been achieved by means of oxidation treatment. Transformation temperatures, friction coefficient and ion release have been determined.

  • Development of provisional extracellular matrix on biomaterials interface: lessons from in vitro cell culture

     Altankov, George Petrov; Groth, Thomas; Gustavsson, Johan Mikael; Engel Lopez, Elisabet; Pegueroles Neyra, Marta; Aparicio, Conrado; Gil Mur, Francisco Javier; Ginebra Molins, Maria Pau; Planell Estany, Josep Antón
    Date of publication: 2010-08-20
    Book chapter

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  • Injectable hydroxyapatite foams for bone regeneration

     Montufar Jimenez, Edgar Benjamin; Planell Estany, Josep Antón; Ginebra Molins, Maria Pau
    TOPEA
    Presentation's date: 2010-07-01
    Presentation of work at congresses

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  • New processing approaches in calcium phosphate cements and their applications in regenerative medicine

     Ginebra Molins, Maria Pau; Español Pons, Montserrat; Montufar Jimenez, Edgar Benjamin; Mestres, Gemma; Perez Antoñanzas, Roman
    International Congress on Biomaterials
    Presentation's date: 2010-03-17
    Presentation of work at congresses

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  • Foamed surfactant solution as a template for self-setting injectable hydroxyapatite scaffolds for bone regeneration

     Montufar Jimenez, Edgar Benjamin; Traykova, Tania Valentinova; Gil, C.; Harr, I.; Almirall Gonzalo, Arturo; Aguirre Cano, Aitor; Engel Lopez, Elisabet; Planell Estany, Josep Antón; Ginebra Molins, Maria Pau
    Acta biomaterialia
    Date of publication: 2010-03
    Journal article

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  • New processing approaches in calcium phosphate cements and their applications in regenerative medicine

     Ginebra Molins, Maria Pau; Español Pons, Montserrat; Montufar Jimenez, Edgar Benjamin; Pérez, Ricardo A.; Mestres Bea, Gemma
    Acta biomaterialia
    Date of publication: 2010-08
    Journal article

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    The key feature of calcium phosphate cements (CPCs) lies in the setting reaction triggered by mixing one or more solid calcium phosphate salts with an aqueous solution. Upon mixture, the reaction takes place through a dissolution–precipitation process which is macroscopically observed by a gradual hardening of the cement paste. The precipitation of hydroxyapatite nanocrystals at body or room temperature, and the fact that those materials can be used as self-setting pastes, have for many years been the most attractive features of CPCs. However, the need to develop materials able to sustain bone tissue ingrowth and be capable of delivering drugs and bioactive molecules, together with the continuous requirement from surgeons to develop more easily handling cements, has pushed the development of new processing routes that can accommodate all these requirements, taking advantage of the possibility of manipulating the self-setting CPC paste. It is the goal of this paper to provide a brief overview of the new processing developments in the area of CPCs and to identify the most significant achievements.

  • Investigation of the hydroxyapatite obtained as hydrolysis product of alpha-tricalcium phosphate by transmission electron microscopy

     Español Pons, Montserrat; Portillo, Joaquim; Manero Planella, Jose M.; Ginebra Molins, Maria Pau
    Crystengcomm
    Date of publication: 2010
    Journal article

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