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  • Development and characterization of biphasic hydroxyapatite/ß-TCP cements

     Gallinetti, Sara; Canal Barnils, Cristina; Ginebra Molins, Maria Pau
    Journal of the American Ceramic Society
    Date of publication: 2014-04
    Journal article

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    Biphasic calcium phosphate bioceramics composed of hydroxyapatite (HA) and ß-tricalcium phosphate (ß-TCP) have relevant properties as synthetic bone grafts, such as tunable resorption, bioactivity, and intrinsic osteoinduction. However, they have some limitations associated to their condition of high-temperature ceramics. In this work self-setting Biphasic Calcium Phosphate Cements (BCPCs) with different HA/ß-TCP ratios were obtained from self-setting a-TCP/ß-TCP pastes. The strategy used allowed synthesizing BCPCs with modulated composition, compressive strength, and specific surface area. Due to its higher solubility, a-TCP was fully hydrolyzed to a calcium-deficient HA (CDHA), whereas ß-TCP remained unreacted and completely embedded in the CDHA matrix. Increasing amounts of the non-reacting ß-TCP phase resulted in a linear decrease of the compressive strength, in association to the decreasing amount of precipitated HA crystals, which are responsible for the mechanical consolidation of apatitic cements. Ca2+ release and degradation in acidic medium was similar in all the BCPCs within the timeframe studied, although differences might be expected in longer term studies once ß-TCP, the more soluble phase was exposed to the surrounding media

    Biphasic calcium phosphate bioceramics composed of hydroxyapatite (HA) and ß-tricalcium phosphate (ß-TCP) have relevant properties as synthetic bone grafts, such as tunable resorption, bioactivity, and intrinsic osteoinduction. However, they have some limitations associated to their condition of high-temperature ceramics. In this work self-setting Biphasic Calcium Phosphate Cements (BCPCs) with different HA/ß-TCP ratios were obtained from self-setting a-TCP/ß-TCP pastes. The strategy used allowed synthesizing BCPCs with modulated composition, compressive strength, and specific surface area. Due to its higher solubility, a-TCP was fully hydrolyzed to a calcium-deficient HA (CDHA), whereas ß-TCP remained unreacted and completely embedded in the CDHA matrix. Increasing amounts of the non-reacting ß-TCP phase resulted in a linear decrease of the compressive strength, in association to the decreasing amount of precipitated HA crystals, which are responsible for the mechanical consolidation of apatitic cements. Ca2+ release and degradation in acidic medium was similar in all the BCPCs within the timeframe studied, although differences might be expected in longer term studies once ß-TCP, the more soluble phase was exposed to the surrounding media

  • Bioactivation of calcium deficient hydroxyapatite with foamed gelatin gel. A new injectable self-setting bone analogue

     Dessi, Mariagemiliana; Alvarez Perez, Marco Antonio; De Santis, Roberto; Ginebra Molins, Maria Pau; Planell Estany, Josep Antón; Ambrosio, Luigi
    Journal of materials science. Materials in medicine
    Date of publication: 2014-02
    Journal article

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    An alternative approach to bone repair for less invasive surgical techniques, involves the development of biomaterials directly injectable into the injury sites and able to replicate a spatially organized platform with features of bone tissue. Here, the preparation and characterization of an innovative injectable bone analogue made of calcium deficient hydroxyapatite and foamed gelatin is presented. The biopolymer features and the cement self-setting reaction were investigated by rheological analysis. The porous architecture, the evolution of surface morphology and the grains dimension were analyzed with electron microscopy (SEM/ESEM/TEM). The physico-chemical properties were characterized by X-ray diffraction and FTIR analysis. Moreover, an injection test was carried out to prove the positive effect of gelatin on the flow ensuing that cement is fully injectable. The cement mechanical properties are adequate to function as temporary substrate for bone tissue regeneration. Furthermore, MG63 cells and bone marrow-derived human mesenchymal stem cells (hMSCs) were able to migrate and proliferate inside the pores, and hMSCs differentiated to the osteoblastic phenotype. The results are paving the way for an injectable bone substitute with properties that mimic natural bone tissue allowing the successful use as bone filler for craniofacial and orthopedic reconstructions in regenerative medicine.

    An alternative approach to bone repair for less invasive surgical techniques, involves the development of biomaterials directly injectable into the injury sites and able to replicate a spatially organized platform with features of bone tissue. Here, the preparation and characterization of an innovative injectable bone analogue made of calcium deficient hydroxyapatite and foamed gelatin is presented. The biopolymer features and the cement self-setting reaction were investigated by rheological analysis. The porous architecture, the evolution of surface morphology and the grains dimension were analyzed with electron microscopy (SEM/ESEM/TEM). The physico-chemical properties were characterized by X-ray diffraction and FTIR analysis. Moreover, an injection test was carried out to prove the positive effect of gelatin on the flow ensuing that cement is fully injectable. The cement mechanical properties are adequate to function as temporary substrate for bone tissue regeneration. Furthermore, MG63 cells and bone marrow-derived human mesenchymal stem cells (hMSCs) were able to migrate and proliferate inside the pores, and hMSCs differentiated to the osteoblastic phenotype. The results are paving the way for an injectable bone substitute with properties that mimic natural bone tissue allowing the successful use as bone filler for craniofacial and orthopedic reconstructions in regenerative medicine.

  • Transportation conditions for prompt use of Ex Vivo expanded and freshly harvested clinical-grade bone marrow mesenchymal stromal/stem cells for bone regeneration

     Giordano, Roberto; Ginebra Molins, Maria Pau
    Tissue Engineering - Part C: Methods
    Date of publication: 2014-03
    Journal article

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    Successful preliminary studies have encouraged a more translational phase for stem cell research. Nevertheless, advances in the culture of human bone marrow-derived mesenchymal stromal/stem cells (hBM-MSC) and osteoconductive qualities of combined biomaterials can be undermined if necessary cell transportation procedures prove unviable. We aimed at evaluating the effect of transportation conditions on cell function, including the ability to form bone in vivo, using procedures suited to clinical application. hBM-MSC expanded in current Good Manufacturing Practice (cGMP) facilities (cGMP-hBM-MSC) to numbers suitable for therapy were transported overnight within syringes and subsequently tested for viability. Scaled-down experiments mimicking shipment for 18 h at 4 C tested the influence of three different clinical-grade transportation buffers (0.9% saline alone or with 4% human serum albumin [HSA] from two independent sources) compared with cell maintenance medium. Cell viability after shipment was >80% in all cases, enabling evaluation of (1) adhesion to plastic flasks and hydroxyapatite tricalcium phosphate osteoconductive biomaterial (HA/ß-TCP 3D scaffold); (2) proliferation rate; (3) ex vivo osteogenic differentiation in contexts of 2D monolayers on plastic and 3D HA/ß-TCP scaffolds; and (4) in vivo ectopic bone formation after subcutaneous implantation of cells with HA/ß-TCP scaffold into NOD/SCID mice. Von Kossa staining was used to assess ex vivo osteogenic differentiation in 3D cultures, providing a quantifiable test of 3D biomineralization ex vivo as a rapid, cost-effective potency assay. Near-equivalent capacities for cell survival, proliferation, and osteogenic differentiation were found for all transportation buffers. Moreover, cGMP-hBM-MSC transported from a production facility under clinical-grade conditions of 4% HSA in 0.9% saline to a destination 18 h away showed prompt adhesion to HA/ß-TCP 3D scaffold and subsequent in vivo bone formation. A successfully validated transportation protocol extends the applicability of fresh stem cells involving multicentric trials for regenerative medicine

  • Calcium phosphate glasses: Silanation process and effect on the bioactivity behavior of Glass-PMMA composites

     Morejon Alonso, lizette; Delgado Garcia-Menocal, Jose Angel; Tarrago Aymerich, Mariona; Alvarez Guichard, Julio Andres; García Vallès, Maite; Martínez Manent, Salvador; Ginebra Molins, Maria Pau
    Journal of biomedical materials research. Part B, Applied biomaterials
    Date of publication: 2014-02-01
    Journal article

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    This article presents the results of a study of the efficiency of silanation process of calcium phosphate glasses particles and its effect on the bioactivity behavior of glass- poly(methyl methacrylate) (PMMA) composites. Two different calcium phosphate glasses: 44.5CaO-44.5P(2)O(5)-11Na(2)O (BV11) and 44.5CaO-44.5P(2)O(5)-6Na(2)O-5TiO(2) (G5) were synthesized and treated with silane coupling agent. The glasses obtained were characterized by Microprobe and BET while the efficiency of silanation process was determined using Fourier Transform Infrared Spectroscopy (FTIR), X-ray Photoelectron Spectroscopy (XPS) and Thermal Analysis (DTA and TG) techniques. The content of coupling agent chemically tightly bond to the silanated glasses ascended to 1.69 +/- 0.02 wt % for BV11sil glass and 0.93 +/- 0.01 wt % for G5sil glass. The in vitro bioactivity test carried out in Simulated Body Fluid (SBF) revealed certain bioactive performance with the use of both silanated glasses in a 30% (by weight) as filler of the PMMA composites because of a superficial deposition of an apatite-like layer with low content of CO32- and HPO42- in its structure after soaking for 30 days occurred. (c) 2013 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 102B: 205-213, 2014.

    This article presents the results of a study of the efficiency of silanation process of calcium phosphate glasses particles and its effect on the bioactivity behavior of glass- poly(methyl methacrylate) (PMMA) composites. Two different calcium phosphate glasses: 44.5CaO-44.5P(2)O(5)-11Na(2)O (BV11) and 44.5CaO-44.5P(2)O(5)-6Na(2)O-5TiO(2) (G5) were synthesized and treated with silane coupling agent. The glasses obtained were characterized by Microprobe and BET while the efficiency of silanation process was determined using Fourier Transform Infrared Spectroscopy (FTIR), X-ray Photoelectron Spectroscopy (XPS) and Thermal Analysis (DTA and TG) techniques. The content of coupling agent chemically tightly bond to the silanated glasses ascended to 1.69 +/- 0.02 wt % for BV11sil glass and 0.93 +/- 0.01 wt % for G5sil glass. The in vitro bioactivity test carried out in Simulated Body Fluid (SBF) revealed certain bioactive performance with the use of both silanated glasses in a 30% (by weight) as filler of the PMMA composites because of a superficial deposition of an apatite-like layer with low content of CO32- and HPO42- in its structure after soaking for 30 days occurred. (c) 2013 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 102B: 205-213, 2014.

  • Access to the full text
    Calcium phosphate neuron-like structures: a rare case or a common structure?  Open access

     Español, M.; Zhao, Z.T.; Almunia, J; Ginebra Molins, Maria Pau
    Journal of materials chemistry B
    Date of publication: 2014-01-01
    Journal article

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    Underneath the unique and beautiful structures of biominerals there is always the presence of organic molecules that tightly interact with the developing inorganic nuclei/crystal directing its growth and assembly towards the final structure. This close interdigitation between organic and inorganic matter renders biominerals not only unique in their appearance but also with exceptional properties. A notable case of such combination is observed when combining double hydrophilic block copolymers (DHBCs) with different ions. In the particular case of calcium phosphate systems, the incorporation of DHBCs was found to induce the formation of unique and delicate neuron-like structures. The present article highlights that such structures are more common than probably expected and they can be created using much simpler organic molecules of a wider nature such as non-ionic surfactants (Tween 80 or Span 20), anionic polymers (sodium polyacrylate) and cationic polymers (polydiallyldimethylammonium chloride). The reaction conditions are however crucial in the stabilization of the structures.

    Underneath the unique and beautiful structures of biominerals there is always the presence of organic molecules that tightly interact with the developing inorganic nuclei/crystal directing its growth and assembly towards the final structure. This close interdigitation between organic and inorganic matter renders biominerals not only unique in their appearance but also with exceptional properties. A notable case of such combination is observed when combining double hydrophilic block copolymers (DHBCs) with different ions. In the particular case of calcium phosphate systems, the incorporation of DHBCs was found to induce the formation of unique and delicate neuron-like structures. The present article highlights that such structures are more common than probably expected and they can be created using much simpler organic molecules of a wider nature such as non-ionic surfactants (Tween 80 or Span 20), anionic polymers (sodium polyacrylate) and cationic polymers (polydiallyldimethylammonium chloride). The reaction conditions are however crucial in the stabilization of the structures.

  • 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.

  • PREMI ICREA ACADEMIA

     Ginebra Molins, Maria Pau
    Participation in a competitive project

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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.

    To characterize three radiopaque Magnesium Phosphate Cements (MPCs) developed for endodontic purposes

  • Role of porosity and pore architecture in the in vivo bone regeneration capacity of biodegradable glass scaffolds

     Sanzana, Edgardo; Navarro Toro, Melba Eugenia; Ginebra Molins, Maria Pau; Planell Estany, Josep Antón; Ojeda, Alvaro; Montecinos, Hernan
    Journal of biomedical materials research. Part A
    Date of publication: 2014-06-01
    Journal article

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    The aim of this work is to shed light on the role of porosity and pore architecture in the in vivo bone regeneration capacity of biodegradable glass scaffolds. A calcium phosphate glass in the system P2O5-CaO-Na2O-TiO2 was foamed using two different porogens, namely albumen and hydrogen peroxide (H2O2); the resulting three-dimensional porous structures were characterized and implanted in New Zealand rabbits to study their in vivo behavior. Scaffolds foamed with albumen displayed a monomodal pore size distribution centered around 150 m and a porosity of 82%, whereas scaffolds foamed with H2O2 showed lower porosity (37%), with larger elongated pores, and multimodal size distribution. After 12 weeks of implantation, histology results revealed a good osteointegration for both types of scaffolds. The quantitative morphometric analysis showed the substitution of the biomaterial by new bone in the case of glasses foamed with albumen. In contrast, bone neoformation and material resorption were significantly lower in the defects filled with the scaffolds foamed with H2O2. The results obtained in this study showed that both calcium phosphate glass scaffolds were osteoconductive, biocompatible, and biodegradable materials. However, differences in porosity, pore architecture, and microstructure led to substantially different in vivo response. (c) 2013 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 102A: 1767-1773, 2014.

    The aim of this work is to shed light on the role of porosity and pore architecture in the in vivo bone regeneration capacity of biodegradable glass scaffolds. A calcium phosphate glass in the system P2O5-CaO-Na2O-TiO2 was foamed using two different porogens, namely albumen and hydrogen peroxide (H2O2); the resulting three-dimensional porous structures were characterized and implanted in New Zealand rabbits to study their in vivo behavior. Scaffolds foamed with albumen displayed a monomodal pore size distribution centered around 150 m and a porosity of 82%, whereas scaffolds foamed with H2O2 showed lower porosity (37%), with larger elongated pores, and multimodal size distribution. After 12 weeks of implantation, histology results revealed a good osteointegration for both types of scaffolds. The quantitative morphometric analysis showed the substitution of the biomaterial by new bone in the case of glasses foamed with albumen. In contrast, bone neoformation and material resorption were significantly lower in the defects filled with the scaffolds foamed with H2O2. The results obtained in this study showed that both calcium phosphate glass scaffolds were osteoconductive, biocompatible, and biodegradable materials. However, differences in porosity, pore architecture, and microstructure led to substantially different in vivo response. (c) 2013 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 102A: 1767-1773, 2014.

  • Development of a low pH cementitious material to enlarge bioreceptivity

     Manso Blanco, Sandra; Mestres Bea, Gemma; Ginebra Molins, Maria Pau; de Belie, Nele; Segura Pérez, Ignacio; Aguado De Cea, Antonio
    Construction & building materials
    Date of publication: 2014-03-15
    Journal article

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    This paper presents a laboratory investigation into the development of a low-pH cementitious material in order to enlarge bioreceptivity. Two different options were tested; reduction of Ordinary Portland Cement (OPC) pH and assessment of the suitability of another hydraulic binder with lower pH, Magnesium-Phosphate Cement (MPC). Regarding OPC, additions of acidic compounds such as boric acid and oxalic acid were investigated. Furthermore, an in-depth characterization of MPC was carried out to evaluate its suitability as a binder for concrete. For this purpose, physico-chemical as well as mechanical properties were tested. (C) 2014 Elsevier Ltd. All rights reserved.

  • 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.

    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 sur- faces, 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 stimu- late bone nucleation and growth from the implant surface. Conclusions The surface quality resulting from this treat- ment 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

  • 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.

    A bone inspired material was obtained by incorporating collagen in the liquid phase of an a -trical- cium 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 com- posite. The morphology and distribution of collagen in the composite was shown to be strongly affected by the col- lagen 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-con- taining cements. The maximum ALP activity was advanced in the collagen-containing cement as compared to the inorganic cement.

  • 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: 2013
    Journal article

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    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.

    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.

  • 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.

    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.

  • 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...

  • 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.

  • 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.

    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 α-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.

  • 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.

    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 0.8 wt%, 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.

    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 (MgNH4PO4·6H2O) 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.

  • Bioactive ceramic and metallic surfaces for bone engineering

     Mas Moruno, Carlos; Español Pons, Montserrat; Montufar Jimenez, Edgar Benjamin; Mestres Bea, Gemma; Aparicio, Conrado; Gil Mur, Francisco Javier; Ginebra Molins, Maria Pau
    Date of publication: 2013-09
    Book chapter

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  • 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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  • Desenvolupament de biomaterials basats em biopolimers d'origen porcí

     Ginebra Molins, Maria Pau; Canal Barnils, Cristina; Español Pons, Montserrat
    Date: 2013-05-15
    Report

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  • Atmospheric Plasma Jet for the Regulation of Drug Release on Bone Biomaterials

     Canal Barnils, Cristina; Modic, Martina; Cvelbar, Uros; Ginebra Molins, Maria Pau
    International Vacuum Congress
    Presentation's date: 2013-09-09
    Presentation of work at congresses

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  • Simvastatin acid release from low-temperature calcium phosphate scaffolds

     Gallinetti, Sara; Pastorino Carraz, David; Canal Barnils, Cristina; Ginebra Molins, Maria Pau
    European Conference on Biomaterials
    Presentation's date: 2013-09-08
    Presentation of work at congresses

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  • Research activities of the biomaterials, biomechanics and tissue engineering group

     Gil Mur, Francisco Javier; Ginebra Molins, Maria Pau; Canal Barnils, Cristina
    Electrical Discharges with liquids for future Applications
    Presentation's date: 2013-10-29
    Presentation of work at congresses

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  • Enhanced adhesion at the interface between PLA fibres and calcium phosphate cements by low temperature plasma improves their mechanical properties

     Canal Barnils, Cristina; Gallinetti, Sara; Ginebra Molins, Maria Pau
    International Symposium on Ceramics in Medicine
    Presentation's date: 2013-11-07
    Presentation of work at congresses

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

     Mestres Bea, 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.

  • 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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  • 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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  • 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.

  • 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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  • 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.

  • BMP-2 release from low-temperature processed calcium phosphate foams

     Montufar Jimenez, Edgar Benjamin; Ben-David, D.; Español Pons, Montserrat; Livne, E.; Ginebra Molins, Maria Pau
    TERMIS World Congress
    Presentation's date: 2012
    Presentation of work at congresses

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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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  • Medalla Narcís Monturiol al mèrit científic i tecnològic

     Ginebra Molins, Maria Pau
    Award or recognition

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  • Biomimetic processing of calcium phosphates: tailoring porosity from the nano- to the macroscale for bone regeneration and drug delivery applications

     Ginebra Molins, Maria Pau; Canal Barnils, Cristina; Montufar Jimenez, Edgar Benjamin; Español Pons, Montserrat
    Conference of the Scandinavian Society for Biomaterials
    Presentation's date: 2012-05-08
    Presentation of work at congresses

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  • Plasmas in organic biomaterials: a case study of polypropylene meshes for soft tissue repair

     Canal Barnils, Cristina; Labay, Cedric; Navarro Santañes, Antonio; Modic, Martina; Cvelbar, Uros; Ginebra Molins, Maria Pau; Canal Arias, Jose Maria
    International Union for Vacuum Science Technique and Applications
    Presentation's date: 2012-12-09
    Presentation of work at congresses

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  • Injectable and flexible tricalcium phosphate/biopolymer composites for bone regeneration

     Maazouz, Yassine; Montufar Jimenez, Edgar Benjamin; Fernandez Albert, Francesc; Ginebra Molins, Maria Pau
    Interdisciplinary Research Conference on Injectable Biomaterials
    Presentation's date: 2012-05-12
    Presentation of work at congresses

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  • Antibiotic-eluting calcium phosphate foams for bone regeneration

     Pastorino Carraz, David; Canal Barnils, Cristina; Ginebra Molins, Maria Pau
    TERMIS World Congress
    Presentation's date: 2012
    Presentation of work at congresses

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  • Using biomaterials to create dynamic and well-controlled changes in the extracellular ionic environment

     Gustavsson, Johan Mikael; Ginebra Molins, Maria Pau; Manero Planella, Jose M.; Engel Lopez, Elisabet
    International Union of Biochemistry and Molecular Biology Congress
    Presentation's date: 2012
    Presentation of work at congresses

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  • Low temperature hydroxyapatite/gelatine robocasted scaffolds for bone tissue engineering

     Maazouz, Yassine; Montufar Jimenez, Edgar Benjamin; Fernandez, F.; Ginebra Molins, Maria Pau
    TERMIS World Congress
    Presentation's date: 2012
    Presentation of work at congresses

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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.

  • 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.