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  • 1.
    Ajaxon, Ingrid
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    Can Bone Void Fillers Carry Load?: Behaviour of Calcium Phosphate Cements Under Different Loading Scenarios2017Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Calcium phosphate cements (CPCs) are used as bone void fillers and as complements to hardware in fracture fixation. The aim of this thesis was to investigate the possibilities and limitations of the CPCs’ mechanical properties, and find out if these ceramic bone cements can carry application-specific loads, alone or as part of a construct. Recently developed experimental brushite and apatite cements were found to have a significantly higher strength in compression, tension and flexion compared to the commercially available CPCs chronOS™ Inject and Norian® SRS®. By using a high-resolution measurement technique the elastic moduli of the CPCs were determined and found to be at least twice as high compared to earlier measurements, and closer to cortical bone than trabecular bone. Using the same method, Poisson's ratio for pure CPCs was determined for the first time. A non-destructive porosity measurement method for wet brushite cements was developed, and subsequently used to study the porosity increase during in vitro degradation. The compressive strength of the experimental brushite cement was still higher than that of trabecular bone after 25 weeks of degradation, showing that the cement can carry high loads over a time span sufficiently long for a fracture to heal. This thesis also presents the first ever fatigue results for acidic CPCs, and confirms the importance of testing the materials under cyclic loading as the cements may fail at stress levels much lower than the material’s quasi-static compressive strength. A decrease in fatigue life was found for brushite cements containing higher amounts of monetite. Increasing porosity and testing in a physiological buffer solution (PBS), rather than air, also decreased the fatigue life. However, the experimental brushite cement had a high probability of surviving loads found in the spine when tested in PBS, which has previously never been accomplished for acidic CPCs. In conclusion, available brushite cements may be able to carry the load alone in scenarios where the cortical shell is intact, the loading is mainly compressive, and the expected maximum stress is below 10 MPa. Under such circumstances this CPC may be the preferred choice over less biocompatible and non-degradable materials.

    List of papers
    1. Mechanical Properties of Brushite Calcium Phosphate Cements
    Open this publication in new window or tab >>Mechanical Properties of Brushite Calcium Phosphate Cements
    2017 (English)In: The World Scientific Encyclopedia of Nanomedicine and Bioengineering II: Bioimplants, Regenerative Medicine, and Nano-Cancer Diagnosis and Phototherapy: Volume 3: Design of Bioactive Materials for Bone Repair and Regeneration / [ed] Shi, D., Singapore: World Scientific Pte Ltd. , 2017Chapter in book (Refereed)
    Place, publisher, year, edition, pages
    Singapore: World Scientific Pte Ltd., 2017
    National Category
    Biomaterials Science Ceramics Medical Materials
    Identifiers
    urn:nbn:se:uu:diva-316712 (URN)978-981-4667-58-6 (ISBN)
    Funder
    Swedish Research Council, GA 621-2011-6258
    Available from: 2017-03-22 Created: 2017-03-22 Last updated: 2017-03-22
    2. Compressive, diametral tensile and biaxial flexural strength of cutting-edge calcium phosphate cements
    Open this publication in new window or tab >>Compressive, diametral tensile and biaxial flexural strength of cutting-edge calcium phosphate cements
    Show others...
    2016 (English)In: Journal of The Mechanical Behavior of Biomedical Materials, ISSN 1751-6161, E-ISSN 1878-0180, Vol. 60, p. 617-627Article in journal (Refereed) Published
    Abstract [en]

    Calcium phosphate cements (CPCs) are widely used in bone repair. Currently there are two main types of CPCs, brushite and apatite. The aim of this project was to evaluate the mechanical properties of particularly promising experimental brushite and apatite formulations in comparison to commercially available brushite- and apatite-based cements (chronOS Inject and Norian® SRS®, respectively), and in particular evaluate the diametral tensile strength and biaxial flexural strength of these cements in both wet and dry conditions for the first time. The cements׳ porosity and their compressive, diametral tensile and biaxial flexural strength were tested in wet (or moist) and dry conditions. The surface morphology was characterized by scanning electron microscopy. Phase composition was assessed with X-ray diffraction. It was found that the novel experimental cements showed better mechanical properties than the commercially available cements, in all loading scenarios. The highest compressive strength (57.2±6.5 MPa before drying and 69.5±6.0 MPa after drying) was found for the experimental brushite cement. This cement also showed the highest wet diametral tensile strength (10.0±0.8 MPa) and wet biaxial flexural strength (30.7±1.8 MPa). It was also the cement that presented the lowest porosity (approx. 12%). The influence of water content was found to depend on cement type, with some cements showing higher mechanical properties after drying and some no difference after drying.

    Keywords
    Calcium phosphate cement; Brushite; Apatite; Compressive strength; Tensile strength; Flexural strength
    National Category
    Ceramics
    Identifiers
    urn:nbn:se:uu:diva-284218 (URN)10.1016/j.jmbbm.2016.03.028 (DOI)000378969100055 ()27082025 (PubMedID)
    Funder
    The Swedish Foundation for International Cooperation in Research and Higher Education (STINT), IG2011-2047Swedish Research Council, 621-2011-6258
    Available from: 2016-04-15 Created: 2016-04-15 Last updated: 2018-08-10Bibliographically approved
    3. Elastic properties and strain-to-crack-initation of calcium phosphate bone cements: Revelations of a high-resolution measurement technique
    Open this publication in new window or tab >>Elastic properties and strain-to-crack-initation of calcium phosphate bone cements: Revelations of a high-resolution measurement technique
    Show others...
    2017 (English)In: Journal of The Mechanical Behavior of Biomedical Materials, ISSN 1751-6161, E-ISSN 1878-0180, Vol. 74, p. 428-437Article in journal (Refereed) Published
    Abstract [en]

    Calcium phosphate cements (CPCs) should ideally have mechanical properties similar to those of the bone tissue the material is used to replace or repair. Usually, the compressive strength of the CPCs is reported and, more rarely, the elastic modulus. Conversely, scarce or no data are available on Poisson's ratio and strain-to-crack-initiation. This is unfortunate, as data on the elastic response is key to, e.g., numerical model accuracy. In this study, the compressive behaviour of brushite, monetite and apatite cements was fully characterised. Measurement of the surface strains was done using a digital image correlation (DIC) technique, and compared to results obtained with the commonly used built-in displacement measurement of the materials testers. The collected data showed that the use of fixed compression platens, as opposed to spherically seated ones, may in some cases underestimate the compressive strength by up to 40%. Also, the built-in measurements may underestimate the elastic modulus by up to 62% as compared to DIC measurements. Using DIC, the brushite cement was found to be much stiffer (24.3 ± 2.3 GPa) than the apatite (13.5 ± 1.6 GPa) and monetite (7.1 ± 1.0 GPa) cements, and elastic moduli were inversely related to the porosity of the materials. Poisson's ratio was determined to be 0.26 ± 0.02 for brushite, 0.21 ± 0.02 for apatite and 0.20 ± 0.03 for monetite. All investigated CPCs showed low strain-to-crack-initiation (0.17–0.19%). In summary, the elastic modulus of CPCs is substantially higher than previously reported and it is concluded that an accurate procedure is a prerequisite in order to properly compare the mechanical properties of different CPC formulations. It is recommended to use spherically seated platens and measuring the strain at a relevant resolution and on the specimen surface.

    National Category
    Ceramics Medical Materials Biomaterials Science
    Identifiers
    urn:nbn:se:uu:diva-316718 (URN)10.1016/j.jmbbm.2017.06.023 (DOI)000410253500046 ()28735216 (PubMedID)
    Funder
    The Swedish Foundation for International Cooperation in Research and Higher Education (STINT), IG2011-2047Swedish Research Council, 621-2011-6258
    Available from: 2017-03-22 Created: 2017-03-22 Last updated: 2017-12-04Bibliographically approved
    4. Evaluation of a porosity measurement method for wet calcium phosphate cements
    Open this publication in new window or tab >>Evaluation of a porosity measurement method for wet calcium phosphate cements
    Show others...
    2015 (English)In: Journal of biomaterials applications, ISSN 0885-3282, E-ISSN 1530-8022, Vol. 30, no 5, p. 526-536Article in journal (Refereed) Published
    Abstract [en]

    The porosity of a calcium phosphate cement is a key parameter as it affects several important properties of the cement. However, a successful, non-destructive porosity measurement method that does not include drying has not yet been reported for calcium phosphate cements. The aim of this study was to evaluate isopropanol solvent exchange as such a method. Two different types of calcium phosphate cements were used, one basic (hydroxyapatite) and one acidic (brushite). The cements were allowed to set in an aqueous environment and then immersed in isopropanol and stored under three different conditions: at room temperature, at room temperature under vacuum (300 mbar) or at 37􏰀C. The specimen mass was monitored regularly. Solvent exchange took much longer time to reach steady state in hydroxyapatite cements compared to brushite cements, 350 and 18 h, respectively. Furthermore, the immersion affected the quasi-static compressive strength of the hydroxyapatite cements. However, the strength and phase composition of the brushite cements were not affected by isopropanol immersion, suggesting that isopropanol solvent exchange can be used for brushite calcium phosphate cements. The main advantages with this method are that it is non-destructive, fast, easy and the porosity can be evaluated while the cements remain wet, allowing for further analysis on the same specimen. 

    Place, publisher, year, edition, pages
    Sage Publications, 2015
    Keywords
    Calcium phosphate, bone cement, porosity, solvent exchange, brushite, hydroxyapatite
    National Category
    Ceramics Biomaterials Science Medical Materials
    Research subject
    Engineering Science with specialization in Materials Science
    Identifiers
    urn:nbn:se:uu:diva-258636 (URN)10.1177/0885328215594293 (DOI)000367743900003 ()26163278 (PubMedID)
    Funder
    The Swedish Foundation for International Cooperation in Research and Higher Education (STINT), IG2011-2047Swedish Research Council, 621-2011-6258
    Available from: 2015-07-17 Created: 2015-07-17 Last updated: 2017-12-04Bibliographically approved
    5. Long-term in vitro degradation of a high-strength brushite cement in water, PBS, and serum solution
    Open this publication in new window or tab >>Long-term in vitro degradation of a high-strength brushite cement in water, PBS, and serum solution
    2015 (English)In: BioMed Research International, ISSN 2314-6133, E-ISSN 2314-6141, article id 575079Article in journal (Refereed) Published
    Abstract [en]

    Bone loss and fractures may call for the use of bone substituting materials, such as calcium phosphate cements (CPCs). CPCs can be degradable, and, to determine their limitations in terms of applications, their mechanical as well as chemical properties need to be evaluated over longer periods of time, under physiological conditions. However, there is lack of data on how the in vitro degradation affects high-strength brushite CPCs over longer periods of time, that is, longer than it takes for a bone fracture to heal. This study aimed at evaluating the long-term in vitro degradation properties of a high-strength brushite CPC in three different solutions: water, phosphate buffered saline, and a serum solution. Microcomputed tomography was used to evaluate the degradation nondestructively, complemented with gravimetric analysis. The compressive strength, chemical composition, and microstructure were also evaluated. Major changes from 10 weeks onwards were seen, in terms of formation of a porous outer layer of octacalcium phosphate on the specimens with a concomitant change in phase composition, increased porosity, decrease in object volume, and mechanical properties. This study illustrates the importance of long-term evaluation of similar cement compositions to be able to predict the material’s physical changes over a relevant time frame. 

    Place, publisher, year, edition, pages
    Hindawi Publishing Corporation, 2015
    Keywords
    Calcium phosphate, brushite, bone cement, degradation, in vitro, solvent exchange, compressive strength, micro-CT, porosity
    National Category
    Ceramics Bio Materials Biomaterials Science Medical Materials
    Research subject
    Engineering Science with specialization in Materials Science
    Identifiers
    urn:nbn:se:uu:diva-265319 (URN)10.1155/2015/575079 (DOI)000364660000001 ()
    Funder
    The Swedish Foundation for International Cooperation in Research and Higher Education (STINT), IG2011-207Swedish Research Council, 621-2011-6258
    Available from: 2015-10-27 Created: 2015-10-27 Last updated: 2017-12-01Bibliographically approved
    6. Compressive fatigue properties of an acidic calcium phosphate cement—effect of phase composition
    Open this publication in new window or tab >>Compressive fatigue properties of an acidic calcium phosphate cement—effect of phase composition
    2017 (English)In: Journal of materials science. Materials in medicine, ISSN 0957-4530, E-ISSN 1573-4838, Vol. 28, no 3, article id 41Article in journal (Refereed) Published
    Abstract [en]

    Calcium phosphate cements (CPCs) are synthetic bone grafting materials that can be used in fracture stabilization and to fill bone voids after, e.g., bone tumour excision. Currently there are several calcium phosphate-based formulations available, but their use is partly limited by a lack of knowledge of their mechanical properties, in particular their resistance to mechanical loading over longer periods of time. Furthermore, depending on, e.g., setting conditions, the end product of acidic CPCs may be mainly brushite or monetite, which have been found to behave differently under quasi-static loading. The objectives of this study were to evaluate the compressive fatigue properties of acidic CPCs, as well as the effect of phase composition on these properties. Hence, brushite cements stored for different lengths of time and with different amounts of monetite were investigated under quasi-static and dynamic compression. Both storage and brushite-to-monetite phase transformation was found to have a pronounced effect both on quasi-static compressive strength and fatigue performance of the cements, whereby a substantial phase transformation gave rise to a lower mechanical resistance. The brushite cements investigated in this study had the potential to survive 5 million cycles at a maximum compressive stress of 13 MPa. Given the limited amount of published data on fatigue properties of CPCs, this study provides an important insight into the compressive fatigue behaviour of such materials. 

    Keywords
    Bone cement, brushite, monetite, fatigue, mechanical properties
    National Category
    Ceramics Medical Materials Biomaterials Science
    Research subject
    Engineering Science with specialization in Materials Science
    Identifiers
    urn:nbn:se:uu:diva-314237 (URN)10.1007/s10856-017-5851-5 (DOI)000394242700006 ()28144853 (PubMedID)
    Funder
    Swedish Research Council, 621-2011-6258
    Available from: 2017-02-03 Created: 2017-01-31 Last updated: 2017-11-29Bibliographically approved
    7. Compressive fatigue properties of a high-strength, degradable calcium phosphate bone cement – influence of porosity and environment
    Open this publication in new window or tab >>Compressive fatigue properties of a high-strength, degradable calcium phosphate bone cement – influence of porosity and environment
    (English)Manuscript (preprint) (Other academic)
    National Category
    Ceramics Medical Materials Biomaterials Science
    Identifiers
    urn:nbn:se:uu:diva-316717 (URN)
    Funder
    Swedish Research Council, 621-2011-6258
    Available from: 2017-03-22 Created: 2017-03-22 Last updated: 2017-03-22
  • 2.
    Ajaxon, Ingrid
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    Acciaioli, Alice
    Istituto Ortopedico Rizzoli, Laboratorio di Tecnologia Medica.
    Lionello, Giacomo
    Istituto Ortopedico Rizzoli, Laboratorio di Tecnologia Medica.
    Ginebra, Maria-Pau
    Biomaterials, Biomechanics and Tissue Engineering Group, Dept. of Materials Science and Metallurgy, Technical University of Catalonia (UPC).
    Öhman, Caroline
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    Baleani, Massimilliano
    Istituto Ortopedico Rizzoli, Laboratorio di Tecnologia Medica.
    Persson, Cecilia
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    Elastic properties and strain-to-crack-initation of calcium phosphate bone cements: Revelations of a high-resolution measurement technique2017In: Journal of The Mechanical Behavior of Biomedical Materials, ISSN 1751-6161, E-ISSN 1878-0180, Vol. 74, p. 428-437Article in journal (Refereed)
    Abstract [en]

    Calcium phosphate cements (CPCs) should ideally have mechanical properties similar to those of the bone tissue the material is used to replace or repair. Usually, the compressive strength of the CPCs is reported and, more rarely, the elastic modulus. Conversely, scarce or no data are available on Poisson's ratio and strain-to-crack-initiation. This is unfortunate, as data on the elastic response is key to, e.g., numerical model accuracy. In this study, the compressive behaviour of brushite, monetite and apatite cements was fully characterised. Measurement of the surface strains was done using a digital image correlation (DIC) technique, and compared to results obtained with the commonly used built-in displacement measurement of the materials testers. The collected data showed that the use of fixed compression platens, as opposed to spherically seated ones, may in some cases underestimate the compressive strength by up to 40%. Also, the built-in measurements may underestimate the elastic modulus by up to 62% as compared to DIC measurements. Using DIC, the brushite cement was found to be much stiffer (24.3 ± 2.3 GPa) than the apatite (13.5 ± 1.6 GPa) and monetite (7.1 ± 1.0 GPa) cements, and elastic moduli were inversely related to the porosity of the materials. Poisson's ratio was determined to be 0.26 ± 0.02 for brushite, 0.21 ± 0.02 for apatite and 0.20 ± 0.03 for monetite. All investigated CPCs showed low strain-to-crack-initiation (0.17–0.19%). In summary, the elastic modulus of CPCs is substantially higher than previously reported and it is concluded that an accurate procedure is a prerequisite in order to properly compare the mechanical properties of different CPC formulations. It is recommended to use spherically seated platens and measuring the strain at a relevant resolution and on the specimen surface.

  • 3.
    Ajaxon, Ingrid
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    Acciaioli, Alice
    Lionello, Giacomo
    Ginebra, Maria-Pau
    Öhman, Caroline
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    Persson, Cecilia
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    Baleani, Massimiliano
    Compressive strength increase of calcium phosphate bone cements is accompanied by a stiffness increase2016Conference paper (Other academic)
  • 4.
    Ajaxon, Ingrid
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    Holmberg, Anders
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    Öhman, Caroline
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    Persson, Cecilia
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    Fatigue performance of a high-strength, degradable calcium phosphate bone cement2018In: Journal of The Mechanical Behavior of Biomedical Materials, ISSN 1751-6161, E-ISSN 1878-0180, Vol. 79, p. 46-52Article in journal (Refereed)
    Abstract [en]

    Calcium phosphate cements (CPCs) are clinically used as injectable materials to fill bone voids and to improve hardware fixation in fracture surgery. In vivo they are dynamically loaded; nonetheless little is known about their fatigue properties. The aim of this study was to, for the first time, investigate the fatigue performance of a high strength, degradable (brushitic) CPC, and also evaluate the effect of cement porosity (by varying the liquid to powder ratio, L/P) and the environment (air at room temperature or in a phosphate buffered saline solution, PBS, at 37 degrees C) on the fatigue life. At a maximum compressive stress level of 15 MPa, the cements prepared with an L/P-ratio of 0.22 and 0.28 ml/g, corresponding to porosities of approximately 12% and 20%, had a 100% probability of survival until run-out of 5 million cycles, in air. When the maximum stress level, or the L/P-ratio, was increased, the probability of survival decreased. Testing in PBS at 37 degrees C led to more rapid failure of the specimens. However, the high-strength cement had a 100% probability of survival up to approximately 2.5 million cycles at a maximum compressive stress level of 10 MPa in PBS, which is substantially higher than some in vivo stress levels, e.g., those found in the spine. At 5 MPa in PBS, all specimens survived to run-out. The results found herein are important if clinical use of the material is to increase, as characterisation of the fatigue performance of CPCs is largely lacking from the literature.

  • 5.
    Ajaxon, Ingrid
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    Holmberg, Anders
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    Öhman Mägi, Caroline
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    Persson, Cecilia
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    Long-term degradation of brushite cements in three different liquids2016Conference paper (Other academic)
  • 6.
    Ajaxon, Ingrid
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    Holmberg, Anders
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    Öhman Mägi, Caroline
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    Persson, Cecilia
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    The influence of porosity on the fatigue properties of brushite cement2016In: Biomaterials for tissue engineering models, 2016Conference paper (Other academic)
  • 7.
    Ajaxon, Ingrid
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    Holmberg, Anders
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    Öhman-Mägi, Caroline
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    Persson, Cecilia
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    Compressive fatigue properties of a high-strength, degradable calcium phosphate bone cement – influence of porosity and environmentManuscript (preprint) (Other academic)
  • 8.
    Ajaxon, Ingrid
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    Lionello, Giacomo
    bLaboratorio di Tecnologia Medica, Istituto Ortopedico Rizzoli, Italy.
    Ginebra, Maria-Pau
    cBiomaterials, Biomechanics and Tissue Engineering Group, Department of Materials Science and Metallurgy, Technical University of Catalonia .
    Öhman, Caroline
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    Baleani, Massimiliano
    bLaboratorio di Tecnologia Medica, Istituto Ortopedico Rizzoli, Italy.
    Persson, Cecilia
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    Local stiffness measurements in apatite and brushite cements2015Conference paper (Other academic)
  • 9.
    Ajaxon, Ingrid
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    Maazouz, Yassine
    Biomaterials, Biomechanics and Tissue Engineering Group, Dept. of Materials Science and Metallurgy, Technical University of Catalonia .
    Ginebra, Maria-Pau
    Biomaterials, Biomechanics and Tissue Engineering Group, Dept. of Materials Science and Metallurgy, Technical University of Catalonia .
    Öhman, Caroline
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    Persson, Cecilia
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    A non-drying porosity evaluation method for calcium phosphate cements2014In: 26th Symposium and Annual Meeting of the International Society for Ceramics in Medicine, 2014, p. 68-68Conference paper (Refereed)
  • 10.
    Ajaxon, Ingrid
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    Maazouz, Yassine
    Ginebra, Maria-Pau
    Öhman, Caroline
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    Persson, Cecilia
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    Evaluation of a porosity measurement method for wet calcium phosphate cements2015In: Journal of biomaterials applications, ISSN 0885-3282, E-ISSN 1530-8022, Vol. 30, no 5, p. 526-536Article in journal (Refereed)
    Abstract [en]

    The porosity of a calcium phosphate cement is a key parameter as it affects several important properties of the cement. However, a successful, non-destructive porosity measurement method that does not include drying has not yet been reported for calcium phosphate cements. The aim of this study was to evaluate isopropanol solvent exchange as such a method. Two different types of calcium phosphate cements were used, one basic (hydroxyapatite) and one acidic (brushite). The cements were allowed to set in an aqueous environment and then immersed in isopropanol and stored under three different conditions: at room temperature, at room temperature under vacuum (300 mbar) or at 37􏰀C. The specimen mass was monitored regularly. Solvent exchange took much longer time to reach steady state in hydroxyapatite cements compared to brushite cements, 350 and 18 h, respectively. Furthermore, the immersion affected the quasi-static compressive strength of the hydroxyapatite cements. However, the strength and phase composition of the brushite cements were not affected by isopropanol immersion, suggesting that isopropanol solvent exchange can be used for brushite calcium phosphate cements. The main advantages with this method are that it is non-destructive, fast, easy and the porosity can be evaluated while the cements remain wet, allowing for further analysis on the same specimen. 

  • 11.
    Ajaxon, Ingrid
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    Persson, Cecilia
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    Mechanical Properties of Brushite Calcium Phosphate Cements2017In: The World Scientific Encyclopedia of Nanomedicine and Bioengineering II: Bioimplants, Regenerative Medicine, and Nano-Cancer Diagnosis and Phototherapy: Volume 3: Design of Bioactive Materials for Bone Repair and Regeneration / [ed] Shi, D., Singapore: World Scientific Pte Ltd. , 2017Chapter in book (Refereed)
  • 12.
    Ajaxon, Ingrid
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    Öhman, Caroline
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    Persson, Cecilia
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    Compressive Fatigue Properties of Acidic Calcium Phosphate Cement2014In: Proceedings of 7th World Congress of Biomechanics, 2014Conference paper (Refereed)
  • 13.
    Ajaxon, Ingrid
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    Öhman, Caroline
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    Persson, Cecilia
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    Long-term in vitro degradation of a high-strength brushite cement in water, PBS, and serum solution2015In: BioMed Research International, ISSN 2314-6133, E-ISSN 2314-6141, article id 575079Article in journal (Refereed)
    Abstract [en]

    Bone loss and fractures may call for the use of bone substituting materials, such as calcium phosphate cements (CPCs). CPCs can be degradable, and, to determine their limitations in terms of applications, their mechanical as well as chemical properties need to be evaluated over longer periods of time, under physiological conditions. However, there is lack of data on how the in vitro degradation affects high-strength brushite CPCs over longer periods of time, that is, longer than it takes for a bone fracture to heal. This study aimed at evaluating the long-term in vitro degradation properties of a high-strength brushite CPC in three different solutions: water, phosphate buffered saline, and a serum solution. Microcomputed tomography was used to evaluate the degradation nondestructively, complemented with gravimetric analysis. The compressive strength, chemical composition, and microstructure were also evaluated. Major changes from 10 weeks onwards were seen, in terms of formation of a porous outer layer of octacalcium phosphate on the specimens with a concomitant change in phase composition, increased porosity, decrease in object volume, and mechanical properties. This study illustrates the importance of long-term evaluation of similar cement compositions to be able to predict the material’s physical changes over a relevant time frame. 

  • 14.
    Ajaxon, Ingrid
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    Öhman Mägi, Caroline
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    Persson, Cecilia
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    Compressive fatigue properties of an acidic calcium phosphate cement—effect of phase composition2017In: Journal of materials science. Materials in medicine, ISSN 0957-4530, E-ISSN 1573-4838, Vol. 28, no 3, article id 41Article in journal (Refereed)
    Abstract [en]

    Calcium phosphate cements (CPCs) are synthetic bone grafting materials that can be used in fracture stabilization and to fill bone voids after, e.g., bone tumour excision. Currently there are several calcium phosphate-based formulations available, but their use is partly limited by a lack of knowledge of their mechanical properties, in particular their resistance to mechanical loading over longer periods of time. Furthermore, depending on, e.g., setting conditions, the end product of acidic CPCs may be mainly brushite or monetite, which have been found to behave differently under quasi-static loading. The objectives of this study were to evaluate the compressive fatigue properties of acidic CPCs, as well as the effect of phase composition on these properties. Hence, brushite cements stored for different lengths of time and with different amounts of monetite were investigated under quasi-static and dynamic compression. Both storage and brushite-to-monetite phase transformation was found to have a pronounced effect both on quasi-static compressive strength and fatigue performance of the cements, whereby a substantial phase transformation gave rise to a lower mechanical resistance. The brushite cements investigated in this study had the potential to survive 5 million cycles at a maximum compressive stress of 13 MPa. Given the limited amount of published data on fatigue properties of CPCs, this study provides an important insight into the compressive fatigue behaviour of such materials. 

  • 15.
    Atif, Abdul Raouf
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Microsystems Technology.
    Pujari-Palmer, Michael
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    Tenje, Maria
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Microsystems Technology.
    Mestres, Gemma
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Microsystems Technology.
    Evaluation of Ionic Interactions of Bone Cement-on-Chip2019Conference paper (Other academic)
    Abstract [en]

    INTRODUCTION: Biomaterials are synthetic materials that can be incorporated into the body to replace an impaired physiological function. Apatite calcium phosphate cements (CPCs), used for bone regeneration, give calcium-deficient hydroxyapatite (CDHA) as an end-product after a dissolution-precipitation reaction during fabrication. CDHA has a tendency to uptake calcium and release phosphate into cell culture medium. Potentially, this leads to depletion of calcium ions in solution, which can be detrimental to cell survival. The aim of this work is to embed CDHA in a microfluidic system and evaluate ion exchange at different flow rates.

    METHODS: CPC paste was cast into a 0.8mm pocket within a Polydimethylsiloxane (PDMS, cured at 60°C for 2h) mould. CPCs were set in 0.9% w/v NaCl at 37°C for 10 days resulting in CDHA. The PDMS containing the CDHA was then bonded to glass, leaving a 0.5mm channel gap. Minimum Essential Media (MEM, 1ml) was pumped through the channel at low (2µl/min), medium (8µl/min) and high (14µl/min) flow rates. A CDHA disc (ø=15mm, h=2mm) was immersed in MEM (1ml) at static conditions (0µl/min) for 24h. Stock Media was taken as control. Calcium and phosphorus concentrations were analysed using Inductively Coupled Plasma Optical Emission Spectroscopy.

    RESULTS & CONCLUSIONS: CDHA was successfully embedded in a microfluidic chip (Fig. 1A). Observed [Ca] and [P] levels were closer to levels in stock MEM at higher flow rates (Fig. 1B). We anticipate that osteoblast viability will improve when grown under flow, as opposed to static conditions, due to continuous replenishment of cell medium.

  • 16. Augustine, Robin
    Arrowroot (Maranta arundinacea) is an edible starch, commercially available as powder, prepared from the roots of the plant family Marantaceae. Arrowroot is well known for its medicinal effects and use as chief ingredient in infant cookies. Arrowroot in film form is prepared and its microwave absorption characteristics, permittivity, loss factor, conductivity, skin depth, and heating coefficient are analyzed. The results are quite promising and can be concluded that arrowroot in film form is a potential candidate for several applications in medical field, when compared with well studied chitosan film2009In: Microwave and Optical Technology Letters, Vol. 51, no 5Article in journal (Refereed)
    Abstract [en]

    Arrowroot (Maranta arundinacea) is an edible starch, commercially available as powder, prepared from the roots of the plant family Marantaceae. Arrowroot is well known for its medicinal effects and use as chief ingredient in infant cookies. Arrowroot in film form is prepared and its microwave absorption characteristics, permittivity, loss factor, conductivity, skin depth, and heating coefficient are analyzed. The results are quite promising and can be concluded that arrowroot in film form is a potential candidate for several applications in medical field, when compared with well studied chitosan film

  • 17. Augustine, Robin
    Biocompatibility study of beta tricalcium phosphate bioceramics and chitosan biopolymer and their use as phantoms for medical imaging applications2009In: Microwave and Optical Technology Letters, Vol. 51, no 12Article in journal (Refereed)
    Abstract [en]

    Beta tricalcium phosphate (b-TCP) bioceramics and chitosan biopolymers are used as biomedical implants because of their better biocompatibility and good bioresorption characteristics. As they are biomaterials, they have good interactions with microwave frequencies. b-TCP and chitosan powder, films, pellets, and gel are prepared and studied at the S-band microwave frequencies. Dielectric parameters such as dielectric constant, dielectric loss, conductivity, and S-parameters are evaluated. Dielectric parameters of different forms of b-TCP and chitosan show resemblance with that of human tissues. Hence, these materials can also be considered as potential phantoms for specific absorption rate measurements as well as in microwave imaging applications. V

  • 18. Augustine, Robin
    Biocompatibility study of hydroxyapatite-chitosan composite for medical applications at microwave frequencies2008In: Microwave and optical technology letters (Print), ISSN 0895-2477, E-ISSN 1098-2760, Vol. 50, no 11, p. 2931-2934Article in journal (Refereed)
    Abstract [en]

    Hydroxyapatite (HAp, Ca10(PO4)6(OH)2) bioceramic and chitosan (poly [(β-1-4) d-glucosamine]) biopolymer show good biocompatibility in vivo. They have biological origin and show excellent interactions with microwave. Microwave study of HAp made using different drying techniques and their composites with chitosan in the ISM band is presented. Pastes are made using HAp and chitosan with different ratios of mixing. The dielectric properties of this composites match with that of human fat, collagen tissues. Some of the compositions exhibit dielectric property close to that of natural bone. This makes them more biocompatible and better substitutes for natural bone. Thus composite bioceramics can be considered as phantom model constituents for imaging purposes.

  • 19.
    Bang, Le Thi
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    Filho, Luimar
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    Engqvist, Håkan
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    Xia, Wei
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    Persson, Cecilia
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    Synthesis and assessment of metallic ion migration through a novel calcium carbonate coating for biomedical implants2019In: Journal of Biomedical Materials Research. Part B - Applied biomaterials, ISSN 1552-4973, E-ISSN 1552-4981Article in journal (Refereed)
  • 20.
    Barba, Albert
    et al.
    Univ Politecn Cataluna, Dept Mat Sci & Met Engn, Biomat Biomech & Tissue Engn Grp, Ave Eduard Maristany 10-14, Barcelona 08019, Spain;Univ Politecn Cataluna, Barcelona Res Ctr Multiscale Sci & Engn, Ave Eduard Maristany 10-14, Barcelona 08019, Spain.
    Diez-Escudero, Anna
    Univ Politecn Cataluna, Dept Mat Sci & Met Engn, Biomat Biomech & Tissue Engn Grp, Ave Eduard Maristany 10-14, Barcelona 08019, Spain;Univ Politecn Cataluna, Barcelona Res Ctr Multiscale Sci & Engn, Ave Eduard Maristany 10-14, Barcelona 08019, Spain.
    Espanol, Montserrat
    Univ Politecn Cataluna, Dept Mat Sci & Met Engn, Biomat Biomech & Tissue Engn Grp, Ave Eduard Maristany 10-14, Barcelona 08019, Spain;Univ Politecn Cataluna, Barcelona Res Ctr Multiscale Sci & Engn, Ave Eduard Maristany 10-14, Barcelona 08019, Spain.
    Bonany, Mar
    Univ Politecn Cataluna, Dept Mat Sci & Met Engn, Biomat Biomech & Tissue Engn Grp, Ave Eduard Maristany 10-14, Barcelona 08019, Spain;Univ Politecn Cataluna, Barcelona Res Ctr Multiscale Sci & Engn, Ave Eduard Maristany 10-14, Barcelona 08019, Spain.
    Maria Sadowska, Joanna
    Univ Politecn Cataluna, Dept Mat Sci & Met Engn, Biomat Biomech & Tissue Engn Grp, Ave Eduard Maristany 10-14, Barcelona 08019, Spain;Univ Politecn Cataluna, Barcelona Res Ctr Multiscale Sci & Engn, Ave Eduard Maristany 10-14, Barcelona 08019, Spain.
    Guillem-Marti, Jordi
    Univ Politecn Cataluna, Dept Mat Sci & Met Engn, Biomat Biomech & Tissue Engn Grp, Ave Eduard Maristany 10-14, Barcelona 08019, Spain;Univ Politecn Cataluna, Barcelona Res Ctr Multiscale Sci & Engn, Ave Eduard Maristany 10-14, Barcelona 08019, Spain.
    Öhman-Mägi, Caroline
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    Persson, Cecilia
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    Manzanares, Maria-Cristina
    Univ Barcelona, Dept Pathol & Expt Therapeut, Human Anat & Embryol Unit, Barcelona 08907, Spain.
    Franch, Jordi
    Univ Autonoma Barcelona, Sch Vet, Small Anim Surg Dept, Bone Healing Grp, E-08193 Barcelona, Spain.
    Ginebra, Maria-Pau
    Univ Politecn Cataluna, Dept Mat Sci & Met Engn, Biomat Biomech & Tissue Engn Grp, Ave Eduard Maristany 10-14, Barcelona 08019, Spain;Univ Politecn Cataluna, Barcelona Res Ctr Multiscale Sci & Engn, Ave Eduard Maristany 10-14, Barcelona 08019, Spain;Barcelona Inst Technol BIST, Inst Bioengn Catalonia IBEC, Barcelona 08028, Spain.
    Impact of Biomimicry in the Design of Osteoinductive Bone Substitutes: Nanoscale Matters2019In: ACS Applied Materials and Interfaces, ISSN 1944-8244, E-ISSN 1944-8252, Vol. 11, no 9, p. 8818-8830Article in journal (Refereed)
    Abstract [en]

    Bone apatite consists of carbonated calcium-deficient hydroxyapatite (CDHA) nanocrystals. Biomimetic routes allow fabricating synthetic bone grafts that mimic biological apatite. In this work, we explored the role of two distinctive features of biomimetic apatites, namely, nanocrystal morphology (plate vs needle-like crystals) and carbonate content, on the bone regeneration potential of CDHA scaffolds in an in vivo canine model. Both ectopic bone formation and scaffold degradation were drastically affected by the nanocrystal morphology after intramuscular implantation. Fine-CDHA foams with needle-like nanocrystals, comparable in size to bone mineral, showed a markedly higher osteoinductive potential and a superior degradation than chemically identical coarse-CDHA foams with larger plate-shaped crystals. These findings correlated well with the superior bone-healing capacity showed by the fine-CDHA scaffolds when implanted intraosseously. Moreover, carbonate doping of CDHA, which resulted in small plate-shaped nanocrystals, accelerated both the intrinsic osteoinduction and the bone healing capacity, and significantly increased the cell-mediated resorption. These results suggest that tuning the chemical composition and the nanostructural features may allow the material to enter the physiological bone remodeling cycle, promoting a tight synchronization between scaffold degradation and bone formation.

  • 21.
    Barba, Albert
    et al.
    Biomaterials, Biomechanics and Tissue Engineering Group, Department of Materials Science and Metallurgical Engineering, Universitat Politecnica de Catalunya.
    Diez-Escudero, Anna
    Biomaterials, Biomechanics and Tissue Engineering Group, Department of Materials Science and Metallurgical Engineering, Universitat Politecnica de Catalunya.
    Maazouz, Yassine
    Biomaterials, Biomechanics and Tissue Engineering Group, Department of Materials Science and Metallurgical Engineering, Universitat Politecnica de Catalunya.
    Rappe, Katrin
    Bone Healing Group, Small Animal Surgery Department, Veterinary School, Universitat Autonoma de Barcelona.
    Espanol, Montserrat
    Barcelona Research Center in Multiscale Science and Engineering, Universitat Politecnica de Catalunya.
    Montufar, Edgar B
    Barcelona Research Center in Multiscale Science and Engineering, Universitat Politecnica de Catalunya.
    Bonany, Mar
    Barcelona Research Center in Multiscale Science and Engineering, Universitat Politecnica de Catalunya.
    Sadowska, Joanna M
    Barcelona Research Center in Multiscale Science and Engineering, Universitat Politecnica de Catalunya.
    Guillem-Marti, Jordi
    Barcelona Research Center in Multiscale Science and Engineering, Universitat Politecnica de Catalunya.
    Öhman, Caroline
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    Persson, Cecilia
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    Manzanares, Maria-Cristina
    Human Anatomy and Embryology Unit, Department of Pathology and Experimental Therapeutics, Universitat de Barcelona.
    Franch, Jordi
    Bone Healing Group, Small Animal Surgery Department, Veterinary School, Universitat Autonoma de Barcelona.
    Ginebra, Maria-Pau
    Biomaterials, Biomechanics and Tissue Engineering Group, Department of Materials Science and Metallurgical Engineering, Universitat Politecnica de Catalunya.
    Osteoinduction by Foamed and 3D-Printed Calcium Phosphate Scaffolds: Effect of Nanostructure and Pore Architecture2017In: ACS Applied Materials and Interfaces, ISSN 1944-8244, E-ISSN 1944-8252, Vol. 9, no 48, p. 41722-41736Article in journal (Refereed)
    Abstract [en]

    Some biomaterials are osteoinductive, that is, they are able to trigger the osteogenic process by inducing the differentiation of mesenchymal stem cells to the osteogenic lineage. Although the underlying mechanism is still unclear, microporosity and specific surface area (SSA) have been identified as critical factors in material-associated osteoinduction. However, only sintered ceramics, which have a limited range of porosities and SSA, have been analyzed so far. In this work, we were able to extend these ranges to the nanoscale, through the foaming and 3D-printing of biomimetic calcium phosphates, thereby obtaining scaffolds with controlled micro- and nanoporosity and with tailored macropore architectures. Calcium-deficient hydroxyapatite (CDHA) scaffolds were evaluated after 6 and 12 weeks in an ectopic-implantation canine model and compared with two sintered ceramics, biphasic calcium phosphate and β-tricalcium phosphate. Only foams with spherical, concave macropores and not 3Dprinted scaffolds with convex, prismatic macropores induced significant ectopic bone formation. Among them, biomimetic nanostructured CDHA produced the highest incidence of ectopic bone and accelerated bone formation when compared with conventional microstructured sintered calcium phosphates with the same macropore architecture. Moreover, they exhibited different bone formation patterns; in CDHA foams, the new ectopic bone progressively replaced the scaffold, whereas in sintered biphasic calcium phosphate scaffolds, bone was deposited on the surface of the material, progressively filling the pore space. In conclusion, this study demonstrates that the high reactivity of nanostructured biomimetic CDHA combined with a spherical, concave macroporosity allows the pushing of the osteoinduction potential beyond the limits of microstructured calcium phosphate ceramics.

  • 22.
    Barba, Albert
    et al.
    Biomaterials, Biomechanics and Tissue Engineering Group, Department of Materials Science and Metallurgical Engineering, Universitat Politècnica de Catalunya.
    Maazouz, Yassine
    Biomaterials, Biomechanics and Tissue Engineering Group, Department of Materials Science and Metallurgical Engineering, Universitat Politècnica de Catalunya.
    Diez-Escudero, Anna
    Biomaterials, Biomechanics and Tissue Engineering Group, Department of Materials Science and Metallurgical Engineering, Universitat Politècnica de Catalunya.
    Rappe, Katrin
    Bone Healing Group, Small Animal Surgery Department, Veterinary School, Universitat Autònoma de Barcelona.
    Espanol, Montserrat
    Biomaterials, Biomechanics and Tissue Engineering Group, Department of Materials Science and Metallurgical Engineering, Universitat Politècnica de Catalunya.
    Montufar, Edgar
    Biomaterials, Biomechanics and Tissue Engineering Group, Department of Materials Science and Metallurgical Engineering, Universitat Politècnica de Catalunya.
    Öhman, Caroline
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    Persson, Cecilia
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    Fontecha, Pedro
    Bone Healing Group, Small Animal Surgery Department, Veterinary School, Universitat Autònoma de Barcelona.
    Manzanares, Maria-Cristina
    Human Anatomy and Embryology Unit, Department of Pathology and Experimental Therapeutics, Universitat de Barcelona.
    Franch, Jordi
    Bone Healing Group, Small Animal Surgery Department, Veterinary School, Universitat Autònoma de Barcelona.
    Ginebra, Maria-Pau
    Biomaterials, Biomechanics and Tissue Engineering Group, Department of Materials Science and Metallurgical Engineering, Universitat Politècnica de Catalunya.
    Osteogenesis by foamed and 3D-printed nanostructured calcium phosphate scaffolds: Effect of pore architecture2018In: Acta Biomaterialia, ISSN 1742-7061, E-ISSN 1878-7568, Vol. 79, p. 135-147Article in journal (Refereed)
    Abstract [en]

    There is an urgent need of synthetic bone grafts with enhanced osteogenic capacity. This can be achieved by combining biomaterials with exogenous growth factors, which however can have numerous undesired side effects, but also by tuning the intrinsic biomaterial properties. In a previous study, we showed the synergistic effect of nanostructure and pore architecture of biomimetic calcium deficient hydroxyapatite (CDHA) scaffolds in enhancing osteoinduction, i.e. fostering the differentiation of mesenchymal stem cells to bone forming cells. This was demonstrated by assessing bone formation after implanting the scaffolds intramuscularly. The present study goes one step forward, since it analyzes the effect of the geometrical features of the same CDHA scaffolds, obtained either by 3D-printing or by foaming, on the osteogenic potential and resorption behaviour in a bony environment. After 6 and 12 weeks of intraosseous implantation, both bone formation and material degradation had been drastically affected by the macropore architecture of the scaffolds. Whereas nanostructured CDHA was shown to be highly osteoconductive both in the robocast and foamed scaffolds, a superior osteogenic capacity was observed in the foamed scaffolds, which was associated with their higher intrinsic osteoinductive potential. Moreover, they showed a significantly higher cell-mediated degradation than the robocast constructs, with a simultaneous and progressive replacement of the scaffold by new bone. In conclusion, these results demonstrate that the control of macropore architecture is a crucial parameter in the design of synthetic bone grafts, which allows fostering both material degradation and new bone formation. Statement of Significance 3D-printing technologies open new perspectives for the design of patient-specific bone grafts, since they allow customizing the external shape together with the internal architecture of implants. In this respect, it is important to design the appropriate pore geometry to maximize the bone healing capacity of these implants. The present study analyses the effect of pore architecture of nanostructured hydroxyapatite scaffolds, obtained either by 3D-printing or foaming, on the osteogenic potential and scaffold resorption in an in vivo model. While nanostructured hydroxyapatite showed excellent osteoconductive properties irrespective of pore geometry, we demonstrated that the spherical, concave macropores of foamed scaffolds significantly promoted both material resorption and bone regeneration compared to the 3D-printed scaffolds with orthogonal-patterned struts and therefore prismatic, convex macropores.

  • 23.
    Barba, Albert
    et al.
    Biomaterials, Biomechanics and Tissue Engineering Group, Department of Materials Science and Metallurgical Engineering, Universitat Politecnica de Catalunya.
    Rappe, Katrin
    Bone Healing Group, Small Animal Surgery Department, Veterinary School, Universitat Autonoma de Barcelona.
    Fontecha, P
    Bone Healing Group, Small Animal Surgery Department, Veterinary School, Universitat Autonoma de Barcelona.
    Diez-Escudero, Anna
    Biomaterials, Biomechanics and Tissue Engineering Group, Department of Materials Science and Metallurgical Engineering, Universitat Politecnica de Catalunya.
    Maazouz, Yassine
    Biomaterials, Biomechanics and Tissue Engineering Group, Department of Materials Science and Metallurgical Engineering, Universitat Politecnica de Catalunya.
    Espanol, Montserrat
    Biomaterials, Biomechanics and Tissue Engineering Group, Department of Materials Science and Metallurgical Engineering, Universitat Politecnica de Catalunya.
    Öhman Mägi, Caroline
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    Persson, Cecilia
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    Manzanares, Maria-Cristina
    Human Anatomy and Embryology Unit, Department of Pathology and Experimental Therapeutics, Universitat de Barcelona.
    Franch, Jordi
    Bone Healing Group, Small Animal Surgery Department, Veterinary School, Universitat Autonoma de Barcelona.
    Ginebra, Maria-Pau
    Biomaterials, Biomechanics and Tissue Engineering Group, Department of Materials Science and Metallurgical Engineering, Universitat Politecnica de Catalunya.
    Nanostructured Calcium Phosphate Scaffolds Trigger Osteoinduction and Osteogenesis2017Conference paper (Refereed)
  • 24.
    Basu, Alex
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Nanotechnology and Functional Materials.
    Celma, Gunta
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Nanotechnology and Functional Materials.
    Strömme, Maria
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Nanotechnology and Functional Materials.
    Ferraz, Natalia
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Nanotechnology and Functional Materials.
    In Vitro and in Vivo Evaluation of the Wound Healing Properties of Nanofibrillated Cellulose Hydrogels2018In: ACS Applied Bio MaterialsArticle in journal (Refereed)
    Abstract [en]

    Current trends in wound care research move toward the development of wound healing dressings designed to treat different types of wounds (e.g., burns and chronic wounds) and toward tailoring treatments for different stages of the wound healing process. In this context, the development of advanced nanotherapeutic materials is highlighted as a promising strategy to efficiently control specific phases of the wound healing process. Here, Ca2+-cross-linked wood-derived nanofibrillated cellulose (NFC) hydrogels are evaluated as wound healing dressings. In vitro biocompatibility assays were performed to study the interaction of the NFC hydrogels with cellular processes that are tightly related to wound healing. Moreover, an in vivo dermo-epidermic full thickness wound healing model in rat was used to uncover the wound healing ability of the Ca2+-cross-linked NFC hydrogels. The in vitro experiments showed that the NFC hydrogels were able to support fibroblast and keratinocyte proliferation. A potential effect of the hydrogels on triggering keratinocyte differentiation was furthermore proposed. In vivo, the NFC hydrogels stimulated healing without causing any adverse local tissue effects, potentially owing to their moisture-donating properties and the herein discussed aiding effect of the Ca2+-cross-linker on epidermal generation. Thus, this work extensively demonstrates the wound healing ability of NFC hydrogels and presents an important milestone in the research on NFC toward advanced wound healing applications.

  • 25.
    Berg, Camilla
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    Engqvist, Håkan
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    Xia, Wei
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    Synthesis of Ion Substituted Ceramic Core-Shell Particles for Dental Applications2018Conference paper (Refereed)
    Abstract [en]

    Calcium phosphate spheres are interesting alternatives for dental applications due to their chemical similarity to teeth and biocompatibility. A spherical shape with a hollow cores allows for loading of therapeutic agents for drug delivery which potentially could be combined with other applications such as tooth remineralization and treatment of hypersensitivity.

    Precipitation reactions are one of the techniques used for synthesizing spherical particles, but little is known about the mechanism behind the sphere formation, which makes tuning of the material properties challenging. Previously, it has been shown that substituting ions can influence the crystallization process, which can enable greater control during the synthesis.In this study, several different substituting ions has been used in the synthesis of alkaline earth phosphates, to further investigate their role in sphere formation and to develop a robust synthesis technique.

    Particles of alkaline earth phosphates (Ca, Sr and Ba) were synthesized with a precipitation reaction. Solutions with constituent anions and cations were mixed at room temperature, and substituting ions (Mg, Ca or Sr) were added before heating at 60-100 °C. Reaction times varied between 10 minutes to 24 hours. Characterization of precipitates was performed with SEM, DLS and FIB to analyze morphology, size and cross-sections of the spheres. Crystal structure and atomic composition was analyzed with XRD and ICP-OES.

    Without substituting ions, precipitates had no specific shape and crystallized in an apatitic structure or as a hydrogenated phosphate. Substituting ions stabilized the initial amorphous phase during the reaction, hindering rapid crystal growth which allowed for self-assembly into hollow, spherical particles with a diameter between 300-700 nm. The phase composition and degree of ion substitution in the precipitates depended on the size and concentration of the substituting ions. The amount of substitution was determined in the range between 5-30 %, where precipitates with a low degree of substitution crystallized in a structure similar to β-tricalcium phosphate, whereas materials with a higher degree of substitution had an amorphous structure.

    In this study it was shown that it was possible to obtain hollow, spherical particles of calcium-, strontium- and barium phosphate, by using substituting ions during a precipitation reaction. This indicates that the approach can be used to tailor the properties of spherical particles intended for dental applications.

  • 26.
    Blasi Romero, Anna
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Nanotechnology and Functional Materials. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Nguyen, Hugo
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Microsystems Technology.
    Barbe, Laurent
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Microsystems Technology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Tenje, Maria
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Microsystems Technology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Mestres, Gemma
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Microsystems Technology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Development and validation of a reusable microfluidic system for the evaluation of biomaterials’ biological properties2019Conference paper (Other academic)
  • 27.
    Cai, Bing
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    Geopolymer-based drug formulations for oral delivery of opioids2014Licentiate thesis, comprehensive summary (Other academic)
    Abstract [en]

    Opioid therapy for chronic pain generally use controlled release formulations to deliver analgesic drugs around-the-clock. Controlled release dosage forms can enlarge the therapeutic effect by controlling the rate and site of release. However, with high drug content, opioid formulations are easily targeted for non-medical use. With the increasing concern of opioid abuse, tamper-resistance becomes an important attribute for opioid controlled-release dosage forms. Geopolymers have been studied as drug carrier for opioids to improve the tamper-resistance but there are still some issues, such as curing condition and fast drug release in acid, have not been studied in detail yet. This thesis focuses on the optimization and evaluation of the geopolymer-based formulation on its controlled-release and tamper-resistance properties with the aim of achieving optimal therapeutic outcomes and reducing abuse potential.

    In this work, we showed some further improvement and evaluations on geopolymer-based drug formulations. The mechanical strength and porosity of geopolymers could be influenced by the curing conditions: high humidity for at least 48 hours could improve its mechanical strength, but elevated temperature only accelerated the geopolymerization but promoted water evaporation, leading to shrinkage and crack formation. Incorporating pH-sensitive organic polymers could improve the acid resistance of geopolymer formulation and thus reduce the risk of dose dumping. Comparing to a commercial opioid tablet, the geopolymer matrix have higher mechanical strength and could offer better resistance against physical manipulation and extraction under heating. The results provided solid experimental support on the potential for geopolymer as matrix for oral opioid delivery systems.

    List of papers
    1. Evaluation of the resistance of a geopolymer-based drug delivery system to tampering
    Open this publication in new window or tab >>Evaluation of the resistance of a geopolymer-based drug delivery system to tampering
    2014 (English)In: International Journal of Pharmaceutics, ISSN 0378-5173, E-ISSN 1873-3476, Vol. 465, no 1-2, p. 169-174Article in journal (Refereed) Published
    Abstract [en]

    Tamper-resistance is an important property of controlled-release formulations of opioid drugs. Tamper-resistant formulations aim to increase the degree of effort required to override the controlled release of the drug molecules from extended-release formulations for the purpose of non-medical use. In this study, the resistance of a geopolymer-based formulation to tampering was evaluated by comparing it with a commercial controlled-release tablet using several methods commonly used by drug abusers. Because of its high compressive strength and resistance to heat, much more effort and time was required to extract the drug from the geopolymer-based formulation. Moreover, in the drug-release test, the geopolymer-based formulation maintained its controlled-release characteristics after milling, while the drug was released immediately from the milled commercial tablets, potentially resulting in dose dumping. Although the tampering methods used in this study does not cover all methods that abuser could access, the results obtained by the described methods showed that the geopolymer matrix increased the degree of effort required to override the controlled release of the drug, suggesting that the formulation has improved resistance to some common drug-abuse tampering methods. The geopolymer matrix has the potential to make the opioid product less accessible and attractive to non-medical users.

    National Category
    Medical Materials
    Research subject
    Engineering Science with specialization in Materials Science
    Identifiers
    urn:nbn:se:uu:diva-219255 (URN)10.1016/j.ijpharm.2014.02.029 (DOI)000333675100022 ()
    Funder
    Swedish Research Council
    Available from: 2014-02-25 Created: 2014-02-25 Last updated: 2018-02-08Bibliographically approved
    2. The effect of curing conditions on compression strength and porosity of metakaolin-based geopolymers
    Open this publication in new window or tab >>The effect of curing conditions on compression strength and porosity of metakaolin-based geopolymers
    2013 (English)In: Developments in Strategic Materials and Computational Design IV, John Wiley & Sons, 2013Conference paper, Published paper (Refereed)
    Abstract [en]

    Geopolymers have been suggested to use as construction, waste treatment and fire proof materials and even drug delivery material due to its excellent mechanical strength, chemical stability and flame resistance. The aim of this study was to investigate the influence of temperature, time and humidity during curing on mechanical strength and porosity of geopolymers.

    The geopolymer precursor paste was obtained by mixing metakaolin, waterglass and de-ionized water. The paste was molded into cylindrical rubber moulds (6  12 mm) and cured under different conditions: i.e. temperatures (ambient temperature, 37°C and 90°C), humidity and time (24, 48 and 96 hours). The compressive strength was determined using a universal testing machine. Helium pycnometer was used to measure the porosity. Via x-ray diffraction the phase composition of the cured samples was determined.

    Elongated curing slightly decreased the total porosity of the tested geopolymers. Higher curing temperature increased the compressive strength after 24 hour but did not affect strength for longer curing times. In general, the samples cured in moisture had higher mechanical strength than those cured in air. But low compression strength of samples cured under high temperature and long time showed that some water content in geopolymer was essential to retaining its microstructure.

    Place, publisher, year, edition, pages
    John Wiley & Sons, 2013
    Series
    Ceramic Engineering and Science Proceedings
    National Category
    Medical Materials
    Identifiers
    urn:nbn:se:uu:diva-219258 (URN)10.1002/9781118807743.ch5 (DOI)
    Conference
    37th International Conference and Expo on Advanced Ceramics and Composites; 27 Jan - 1 Feb 2013; Daytona Beach, Fia., USA
    Funder
    Swedish Research Council
    Available from: 2014-02-25 Created: 2014-02-25 Last updated: 2018-02-08Bibliographically approved
    3.
    The record could not be found. The reason may be that the record is no longer available or you may have typed in a wrong id in the address field.
  • 28.
    Cai, Bing
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    Engqvist, Håkan
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    Bredenberg, Susanne
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    Evaluation of the resistance of a geopolymer-based drug delivery system to tampering2014In: International Journal of Pharmaceutics, ISSN 0378-5173, E-ISSN 1873-3476, Vol. 465, no 1-2, p. 169-174Article in journal (Refereed)
    Abstract [en]

    Tamper-resistance is an important property of controlled-release formulations of opioid drugs. Tamper-resistant formulations aim to increase the degree of effort required to override the controlled release of the drug molecules from extended-release formulations for the purpose of non-medical use. In this study, the resistance of a geopolymer-based formulation to tampering was evaluated by comparing it with a commercial controlled-release tablet using several methods commonly used by drug abusers. Because of its high compressive strength and resistance to heat, much more effort and time was required to extract the drug from the geopolymer-based formulation. Moreover, in the drug-release test, the geopolymer-based formulation maintained its controlled-release characteristics after milling, while the drug was released immediately from the milled commercial tablets, potentially resulting in dose dumping. Although the tampering methods used in this study does not cover all methods that abuser could access, the results obtained by the described methods showed that the geopolymer matrix increased the degree of effort required to override the controlled release of the drug, suggesting that the formulation has improved resistance to some common drug-abuse tampering methods. The geopolymer matrix has the potential to make the opioid product less accessible and attractive to non-medical users.

  • 29.
    Cai, Bing
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    Engqvist, Håkan
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    Bredenberg, Susanne
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    Mellgren, Torbjörn
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    The effect of curing conditions on compression strength and porosity of metakaolin-based geopolymers2013In: Developments in Strategic Materials and Computational Design IV, John Wiley & Sons, 2013Conference paper (Refereed)
    Abstract [en]

    Geopolymers have been suggested to use as construction, waste treatment and fire proof materials and even drug delivery material due to its excellent mechanical strength, chemical stability and flame resistance. The aim of this study was to investigate the influence of temperature, time and humidity during curing on mechanical strength and porosity of geopolymers.

    The geopolymer precursor paste was obtained by mixing metakaolin, waterglass and de-ionized water. The paste was molded into cylindrical rubber moulds (6  12 mm) and cured under different conditions: i.e. temperatures (ambient temperature, 37°C and 90°C), humidity and time (24, 48 and 96 hours). The compressive strength was determined using a universal testing machine. Helium pycnometer was used to measure the porosity. Via x-ray diffraction the phase composition of the cured samples was determined.

    Elongated curing slightly decreased the total porosity of the tested geopolymers. Higher curing temperature increased the compressive strength after 24 hour but did not affect strength for longer curing times. In general, the samples cured in moisture had higher mechanical strength than those cured in air. But low compression strength of samples cured under high temperature and long time showed that some water content in geopolymer was essential to retaining its microstructure.

  • 30.
    Cai, Bing
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    Xia, Wei
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    Bredenberg, Susanne
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    Li, Hao
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery.
    Engqvist, Håkan
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    Bioceramic microneedles with flexible and self-swelling substrate2015In: European journal of pharmaceutics and biopharmaceutics, ISSN 0939-6411, E-ISSN 1873-3441, Vol. 94, p. 404-410Article in journal (Refereed)
    Abstract [en]

    To reduce the effort required to penetrate the skin and optimize drug release profiles, bioceramic microneedle arrays with higher-aspect-ratio needles and a flexible and self-swelling substrate have been developed. Swelling of the substrate can assist in separating it from the needles and leave them in the skin as a drug depot. The preparation procedures for this bioceramic microneedle are described in the paper. Clonidine hydrochloride, the model drug, was released in a controlled manner by the microneedle device in vitro. Results showed that the microneedle array with a flexible and self-swelling substrate released the drug content faster than the array with a rigid substrate. Disintegration of the needle material and diffusion of the drug molecules are believed as the main control mechanisms of the drug release from these microneedle arrays. Ex vivo skin penetration showed that they can effectively penetrate the stratum corneum without an extra device. This work represents a progression in the improvement of bioceramic microneedles for transdermal drug delivery.

  • 31.
    Cai, Yanling
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Nanotechnology and Functional Materials.
    Engqvist, Håkan
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    Strømme, Maria
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Nanotechnology and Functional Materials.
    Welch, Ken
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Nanotechnology and Functional Materials.
    Biofilm elimination and detachment using photocatalytic TiO2 surfaces2011In: Conference, 2011Conference paper (Refereed)
  • 32.
    Cai, Yanling
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Nanotechnology and Functional Materials.
    Engqvist, Håkan
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    Strømme, Maria
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Nanotechnology and Functional Materials.
    Welch, Ken
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Nanotechnology and Functional Materials.
    Biofilm susceptibility to photocatalytic dental mateirals2011In: Conference, 2011Conference paper (Refereed)
  • 33.
    Cai, Yixiao
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    Edin, Fredrik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery.
    Jin, Zhe
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Physiology.
    Alexsson, Andrei
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Rheumatology.
    Gudjonsson, Olafur
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Liu, Wei
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery.
    Rask-Andersen, Helge
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery.
    Karlsson, Mikael
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    Li, Hao
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery.
    Strategy towards independent electrical stimulation from cochlear implants: Guided auditory neuron growth on topographically modified nanocrystalline diamond2016In: Acta Biomaterialia, ISSN 1742-7061, E-ISSN 1878-7568, Vol. 31, p. 211-220Article in journal (Refereed)
    Abstract [en]

    Cochlear implants (CI) have been used for several decades to treat patients with profound hearing loss. Nevertheless, results vary between individuals, and fine hearing is generally poor due to the lack of discrete neural stimulation from the individual receptor hair cells. A major problem is the deliverance of independent stimulation signals to individual auditory neurons. Fine hearing requires significantly more stimulation contacts with intimate neuron/electrode interphases from ordered axonal re-growth, something current CI technology cannot provide.

    Here, we demonstrate the potential application of micro-textured nanocrystalline diamond (NCD) surfaces on CI electrode arrays. Such textured NCD surfaces consist of micrometer-sized nail-head-shaped pillars (size 5 5 lm2) made with sequences of micro/nano-fabrication processes, including sputtering, photolithography and plasma etching.

    The results show that human and murine inner-ear ganglion neurites and, potentially, neural progenitor cells can attach to patterned NCD surfaces without an extracellular matrix coating. Microscopic methods revealed adhesion and neural growth, specifically along the nail-head-shaped NCD pillars in an ordered manner, rather than in non-textured areas. This pattern was established when the inter-NCD pillar distance varied between 4 and 9 lm.

    The findings demonstrate that regenerating auditory neurons show a strong affinity to the NCD pillars, and the technique could be used for neural guidance and the creation of new neural networks. Together with the NCD’s unique anti-bacterial and electrical properties, patterned NCD surfaces could provide designed neural/electrode interfaces to create independent electrical stimulation signals in CI electrode arrays for the neural population.

  • 34.
    Carlsson, Elin
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics. Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    Mestres, Gemma
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    Treerattrakoon, Kiatnida
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Lopez, Alejandro
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    Karlsson Ott, Marjam
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    Larsson, Sune
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Persson, Cecilia
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    In vitro and in vivo response to low-modulus PMMA-based bone cement2015In: BioMed Research International, ISSN 2314-6133, E-ISSN 2314-6141, article id 594284Article in journal (Refereed)
    Abstract [en]

    The high stiffness of acrylic bone cements has been hypothesized to contribute to the increased number of fractures encountered after vertebroplasty, which has led to the development of low-modulus cements. However, there is no data available on the in vivo biocompatibility of any low-modulus cement. In this study, the in vitro cytotoxicity and in vivo biocompatibility of two types of low-modulus acrylic cements, one modified with castor oil and one with linoleic acid, were evaluated using human osteoblast-like cells and a rodent model, respectively. While the in vitro cytotoxicity appeared somewhat affected by the castor oil and linoleic acid additions, no difference could be found in the in vivo response to these cements in comparison to the base, commercially available cement, in terms of histology and flow cytometry analysis of the presence of immune cells. Furthermore, the in vivo radiopacity of the cements appeared unaltered. While these results are promising, the mechanical behavior of these cements in vivo remains to be investigated.

  • 35.
    Chen, Song
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    Yu, Shun
    Engqvist, Håkan
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    Xia, Wei
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    Synthesis and characterization of monetite with thin nacreous structure2016Conference paper (Refereed)
  • 36.
    Chen, Song
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    Öhman, Caroline
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    Jefferies, Steven R.
    Gray, Holly
    Xia, Wei
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    Engqvist, Håkan
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    Quasi-static compressive strength and compressive fatigue limit of dental cements2016Conference paper (Refereed)
  • 37.
    Cheung, Ocean
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Nanotechnology and Functional Materials.
    Vall, Maria
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Nanotechnology and Functional Materials.
    Sun, Rui
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Nanotechnology and Functional Materials.
    Strömme, Maria
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Nanotechnology and Functional Materials.
    Novel mesoporous amorphous magnesium carbonate for the adsorption of textile dyes and heavy metal ions2018Conference paper (Refereed)
  • 38.
    Díez-Escudero, Anna
    et al.
    Univ Politecn Cataluna, Dept Mat Sci & Met Engn, Biomat Biomech & Tissue Engn Grp, EEBE, Ave Eduard Maristany 10-14, Barcelona 08019, Spain; Univ Politecn Cataluna, Barcelona Res Ctr Multiscale Sci & Engn, EEBE, Ave Eduard Maristany 10-14, Barcelona 08019, Spain.
    Montserrat, Espanol
    Univ Politecn Cataluna, Dept Mat Sci & Met Engn, Biomat Biomech & Tissue Engn Grp, EEBE, Ave Eduard Maristany 10-14, Barcelona 08019, Spain Univ Politecn Cataluna, Barcelona Res Ctr Multiscale Sci & Engn, EEBE, Ave Eduard Maristany 10-14, Barcelona 08019, Spain.
    Bonany, Mar
    Univ Politecn Cataluna, Dept Mat Sci & Met Engn, Biomat Biomech & Tissue Engn Grp, EEBE, Ave Eduard Maristany 10-14, Barcelona 08019, Spain Univ Politecn Cataluna, Barcelona Res Ctr Multiscale Sci & Engn, EEBE, Ave Eduard Maristany 10-14, Barcelona 08019, Spain.
    Lu, Xi
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    Persson, Cecilia
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    Ginebra, Maria-Pau
    Univ Politecn Cataluna, Dept Mat Sci & Met Engn, Biomat Biomech & Tissue Engn Grp, EEBE, Ave Eduard Maristany 10-14, Barcelona 08019, Spain Univ Politecn Cataluna, Barcelona Res Ctr Multiscale Sci & Engn, EEBE, Ave Eduard Maristany 10-14, Barcelona 08019, Spain; Barcelona Inst Sci & Technol, Inst Bioengn Catalonia IBEC, C Baldiri Reixac 10-12, Barcelona 08028, Spain .
    Heparinization of Beta Tricalcium Phosphate: Osteo-immunomodulatory Effects2018In: Advanced Healthcare Materials, ISSN 2192-2640, E-ISSN 2192-2659, Vol. 7, no 5, article id 1700867Article in journal (Refereed)
    Abstract [en]

    Immune cells play a vital role in regulating bone dynamics. This has boosted the interest in developing biomaterials that can modulate both the immune and skeletal systems. In this study, calcium phosphates discs (i.e., beta-tricalcium phosphate, β-TCP) are functionalized with heparin to investigate the effects on immune and stem cell responses. The results show that the functionalized surfaces downregulate the release of hydrogen peroxide and proinflammatory cytokines (tumor necrosis factor alpha and interleukin 1 beta) from human monocytes and neutrophils, compared to nonfunctionalized discs. The macrophages show both elongated and round shapes on the two ceramic substrates, but the morphology of cells on heparinized β-TCP tends toward a higher elongation after 72 h. The heparinized substrates support rat mesenchymal stem cell (MSC) adhesion and proliferation, and anticipate the differentiation toward the osteoblastic lineage as compared to β-TCP and control. The coupling between the inflammatory response and osteogenesis is assessed by culturing MSCs with the macrophage supernatants. The downregulation of inflammation in contact with the heparinized substrates induces higher expression of bone-related markers by MSCs.

  • 39.
    Díez-Escudero, Anna
    et al.
    Technical University of Catalonia, Spain & Barcelona Research Center of Multiscale Science and Engineering, Spain.
    Montserrat, Espanol
    Technical University of Catalonia, Spain & Barcelona Research Center of Multiscale Science and Engineering, Spain.
    Di Pompo, Gemma
    Istituto Ortopedico Rizzoli, Italy.
    Torregianni, Elena
    Istituto Ortopedico Rizzoli, Italy.
    Persson, Cecilia
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    Ciapetti, Gabriela
    Istituto Ortopedico Rizzoli, Italy.
    Baldini, Nicola
    Istituto Ortopedico Rizzoli, Italy.
    Ginebra, Maria-Pau
    Technical University of Catalonia, Spain & Barcelona Research Center of Multiscale Science and Engineering, Spain.
    Heparinisation as a tool to modulate osteoclastogenesis on calcium phosphates2017Conference paper (Refereed)
  • 40.
    Engstrand Unosson, Johanna
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    Persson, Cecilia
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    Engqvist, Håkan
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    An evaluation of methods to determine the porosity of calcium phosphate cements2015In: Journal of Biomedical Materials Research. Part B - Applied biomaterials, ISSN 1552-4973, E-ISSN 1552-4981, Vol. 103, no 1, p. 62-71Article in journal (Refereed)
    Abstract [en]

    The porosity of a material can be determined using a diversity of methods; however, the results from these methods have so far not been compared and analyzed for calcium phosphate cements (CPCs). The aim of this study was to compare a fast and easy method for porosity measurements with some commonly used porosity methods for CPCs. The investigated method is based on the assumption that when a wet cement sample is dried, the volume of the evaporated water is equal to the volume of pores within the cement. Moreover, different methods of drying the cements were evaluated for acidic CPCs. The results showed that drying at room temperature (22°C ±1°C) is preferable, since a phase transformation was observed at higher temperatures. The results also showed that drying for 24 hours in vacuum was sufficient to achieve water free cements. The porosity measured was found to vary between the porosity methods evaluated herein, and to get a complete picture of a cement’s porosity more than one method is recommended. Water evaporation, is, however, a fast and easy method to estimate the porosity of CPCs and could simplify porosity measurements in the future.

  • 41.
    Ferraz, Natalia
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Nanotechnology and Functional Materials.
    Nanocellulose for biomedical applications2018In: Uppsala Biomaterials and Bioengineering Meeting September 4th, 2018., 2018Conference paper (Refereed)
  • 42.
    Ferraz, Natalia
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Nanotechnology and Functional Materials.
    Hoess, Andreas
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    Thormann, Annika
    Heilmann, Andreas
    Shen, Jinhui
    Tang, Liping
    Karlsson Ott, Marjam
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    Role of Alumina Nanoporosity in Acute Cell Response2011In: Journal of Nanoscience and Nanotechnology, ISSN 1533-4880, E-ISSN 1533-4899, Vol. 11, no 8, p. 6698-6704Article in journal (Refereed)
    Abstract [en]

    This work studied the effect of nanoporous alumina in acute cellular response in an in vivo model. Nanoporous alumina membranes, with pore size diameters of 20 and 200 nm, were fabricated by anodic oxidation of aluminium. The membranes were thereafter characterized in terms of pore size distribution and chemical composition. To evaluate acute inflammatory response, the membranes were implanted in the peritoneal cavity of mice. Cell recruitment to the implant site was determined by fluorescence activated cell sorting (FACS) analysis. Cell adhesion to material surfaces was studied in terms of cell number, type, and morphology using scanning electron microscopy (SEM) and immunocytochemical staining followed by fluorescence microscopy. The fabricated nanoporous alumina membranes were found to have narrow pore size distribution. The in vivo study showed that 200 nm alumina membranes induced stronger inflammatory response than 20 nm membranes. This was reflected by the number of implant-associated phagocytes and the number of cells recruited to the implantation site. Since both pore-size membranes possess similar chemical composition, we believe that the observed difference in cell recruitment and adhesion is an effect of the material nanotopography. Our results suggest that nanotopography can be used to subtly control the recruitment and adherence of phagocytic cells during the acute inflammatory response to alumina membranes.

  • 43.
    Ferraz, Natalia
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Nanotechnology and Functional Materials.
    Strømme, Maria
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Nanotechnology and Functional Materials.
    Fellström, Bengt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Pradhan, Sulena
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Nanotechnology and Functional Materials.
    Nyholm, Leif
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - Ångström, Inorganic Chemistry.
    Mihranyan, Albert
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Nanotechnology and Functional Materials.
    In vitro and in vivo toxicity of rinsed and aged nanocellulose-polypyrrole composites2012In: Journal of Biomedical Materials Research. Part A, ISSN 1549-3296, E-ISSN 1552-4965, Vol. 100A, no 8, p. 2128-2138Article in journal (Refereed)
    Abstract [en]

    Novel composites of nanocellulose and the conducting polymer polypyrrole (PPy) are herein suggested as potential candidates for active ion-extraction membranes in electrochemically controlled hemodialysis. This work has defined processing parameters to obtain a biocompatible nanocellulose-PPy composite and for the first time, the effect of the composite ageing on cell viability has been studied.

    The influence of rinsing and extraction process steps, as well as ageing under different conditions (i.e. in air, at –20 ˚C and in argon), on the electroactivity and cytotoxicity of a PPy-nanocellulose composite has been investigated. The biocompatibility evaluation was based on indirect toxicity assays with fibroblasts and monocyte cell lines and an acute toxicity test in mice, while the electroactivity was evaluated by cyclic voltammetry experiments.

    The as-prepared composite did not induce any cytotoxic response in vitro or in vivo. Extensive rinsing and 48 hour incubation in biological buffer previous to the preparation of the culture medium extracts were, however, necessary to obtain a non-cytotoxic composite. The as-prepared composite was also found to exhibit acceptable electrochemical performance, which was retained upon 4 weeks storage in argon atmosphere.  It was shown that ageing of the composite had a negative effect on biocompatibility, regardless of the storage condition. Thus, to allow for long time storage of electroactive nanocellulose-PPy hemodialysis membranes, the degradation of PPy upon storage must be controlled. The present results show that the biocompatibility of PPy composites depends on the rinsing and pre-treatment of the composite material as well as the aging of the material.

  • 44.
    Forsgren, Johan
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Nanotechnology and Functional Materials.
    Paz, María Dolores
    León, Betty
    Engqvist, Håkan
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    Laser induced surface structuring and ion conversion in the surface oxide of titanium: possible implications for the wetability of laser treated implants.2013In: Journal of materials science. Materials in medicine, ISSN 0957-4530, E-ISSN 1573-4838, Vol. 24, no 1, p. 11-15Article in journal (Refereed)
    Abstract [en]

    In the present study, commercially pure titanium was irradiated with UV-light with varying wavelengths using a Q-switched Nd:YAG-laser. This was performed in order to investigate if a laser treatment can be employed to rapidly introduce hydrophilic properties to titanium surfaces, which is believed to facilitate protein adsorption and cell attachment. It was demonstrated that irradiation with 355 nm light (10 Hz, 90 mJ/shot) for 1 min or more caused an ion conversion of Ti(4+) to Ti(3+) sites in the surface oxide which lead to an increase in hydrophilicity of the surface. Furthermore, shorter irradiation times at 355 nm caused a surface structuring that gave rise to an unexpected and unstable hydrophobic state at the surface. Irradiation with 266 nm light (10 Hz, 40 mJ/shot) did not introduce any ion conversion in the surface oxide, nor did it give rise to any hydrophobicity of the surface.

  • 45.
    Fowler, Lee
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    Development of titanium-copper alloys for dental applications2019Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Titanium alloys find wide application in the medical implants industry, which includes areas of orthopaedic and dental implants. The reason for the popularity of the material is high mechanical strength, low density, and reported growth of bone onto the material, as well as corrosion resistance. Despite the general success of titanium materials, a drawback is that it is vulnerable to bacterial colonization, which can cause implant failure through inflammatory diseases. Peri-implantitis is one such disease, which can lead to irreversible bone loss and subsequently implant instability.

    This thesis focuses on the use of copper (Cu) as an antibacterial element in titanium alloys, where the purpose is designing inherently antibacterial materials.

    With an understanding that copper can reduce bacterial populations by ion release of Cu into solutions, as well as by direct contact of bacteria with Cu surfaces: studies on the effect of Cu ions on bacteria and cells were conducted, in addition to studies on Ti-Cux alloys.

    Varying Cu concentrations in solution were introduced to bacteria (Staphylococcus epidermidis) and cells (MC3T3 murine calvarial osteoblasts), and it was found that the lethal dosage for Cu ions was in the range from 9x10-5 to 9x10-6 g/ml, for bacteria and cells. The Cu ions were also found to cause a stress response for this bacteria at concentrations between 9x10-6 to 9x10-7 g/ml, and recommended to be avoided for implant materials.

    For Ti-Cux binary alloys, studies established that a 10wt%Cu alloy, which released 9x10-8 g/ml, reduced the bacterial population by 27 % in 6 hours in a direct contact test. This alloy was found to be composed of intermetallic (Ti2Cu) and hexagonal closed packed titanium (HCP-Ti) crystals. A separate study on aged heat treated Ti-Cux alloys, showed that an additional phase of Ti3Cu was present in lower volume fraction. The aged alloys of Ti-Cux showed higher volume fraction of Ti2Cu but only a slightly higher antibacterial ability, compared to those without ageing. The hardness of the Ti-Cux alloys was however detrimentally affected by ageing, especially for the 10wt%Cu alloy.

    Investigations on the alloying of Cu with an existing implant alloy, Ti-10wt%Ta-1.6wt%Nb-1.7wt%Zr (TNTZ), was also performed and at higher wt%Cu alloys with three-phased microstructures were present. Alloying of Cu in the TNTZ material increased hardness and with further development of this novel alloy, a potential biomaterial for clinical applications could be designed.

    In conclusion, the results of this thesis demonstrate that the use of Cu in proximity to cells and bacteria requires dose dependent consideration for material design, so that antibacterial materials can be developed that do not harm tissue. The appropriate design of alloys can also be performed so as to allow antibacterial ability to be achieved, along with ensuring appropriate mechanical and corrosion properties. Furthermore, Cu as an antibacterial element can be alloyed into various titanium alloy systems and with further development in this area; antibacterial alloys could benefit the implant industry and patients alike.

    List of papers
    1. Effect of copper ion concentration on bacteria and cells
    Open this publication in new window or tab >>Effect of copper ion concentration on bacteria and cells
    2019 (English)In: MDPI Materials Biomaterial, ISSN 1996-1944Article in journal (Refereed) Submitted
    Abstract [en]

    In the oral cavity dental implants - most often made of commercially pure titanium - come in contact with bacteria, and antibacterial management has been researched extensively to improve patient care. Antibiotic resistance becoming increasingly prevalent, have resulted in copper being investigated as an antibacterial element in alloys. In this study the objective was to investigate the copper ion concentrations at which cyto-toxicity is avoided while bacterial inhibition is ensured, by comparing Cu ion effects on selected eukaryotes and prokaryotes. To determine relevant copper ion concentrations, ion release rates from copper and a 10wt%Cu Ti-alloy were investigated. Survival studies were performed on MC3T3 cells and Staphylococcus epidermidis bacteria, after exposure to Cu ions concentrations ranging from 9x10-3 to 9x10-12 g/ml. Cell survival increased from <10% to >90% after 24 hours of exposure, by reducing Cu concentrations from 9x10-5 to 9x10-6 g/ml. Survival of bacteria also increased in the same range of Cu concentrations. The maximum bacteria growth was found at 9x10-7 g/ml, probably due to stress response. In conclusion, the minimum inhibitory concentrations of Cu ions for these prokaryotes and eukaryotes were found in the range from 9x10-5 to 9x10-6 g/ml. Interestingly the Cu ion concentration correlating to the release rate of the 10wt%Cu alloy (9x10-8 g/ml) did not kill the bacteria, although this alloy has previously been found to be antibacterial. Further studies should investigate in-depth the bacteria killing mechanism of copper.

    Keywords
    Copper ion, Ion release, Antibacterial, S. Epidermidis, MC3T3
    National Category
    Other Materials Engineering
    Identifiers
    urn:nbn:se:uu:diva-395279 (URN)
    Available from: 2019-10-16 Created: 2019-10-16 Last updated: 2019-10-17
    2. Antibacterial investigation of titanium-copper alloys using luminescent Staphylococcus epidermidis in a direct contact test
    Open this publication in new window or tab >>Antibacterial investigation of titanium-copper alloys using luminescent Staphylococcus epidermidis in a direct contact test
    Show others...
    2019 (English)In: Materials science & engineering. C, biomimetic materials, sensors and systems, ISSN 0928-4931, E-ISSN 1873-0191, Vol. 97, p. 707-714Article in journal (Refereed) Published
    Abstract [en]

    Commercially pure titanium (CP-Ti), used as oral implants, is often populated by various bacterial colonies in the oral cavity. These bacteria can cause Peri-implantitis, leading to loss of bone tissue and failure of implants. With the increased awareness of antibiotic resistance, research has been directed towards alternative solutions and recent findings have indicated titanium-copper (Ti-Cu) alloys as a promising antibacterial material. The aim of this study was to produce homogeneous Ti-Cu alloys, with various concentrations of copper, and to characterise their antibacterial properties through direct contact tests, using luminescent bacteria, in addition to traditional materials characterisation techniques. Samples of CP-Ti and four different Ti-Cu alloys (1, 2.5, 3 and 10 wt%Cu) were produced in an arc-furnace, heated treated and rapidly quenched. X-ray diffraction revealed that Ti2Cu, was present only in the 10 wt%Cu alloy, however, scanning electron microscopy (SEM) indicated precipitates at the grain boundaries of the 3 wt%Cu alloy, which were confirmed to be of a copper rich phase by energy dispersive x-ray spectroscopy (EDS) analysis. EDS line scans confirmed that the alloys were homogenous. After 6 h, a trend between copper content and antibacterial rate could be observed, with the 10 wt%Cu alloy having the highest rate. SEM confirmed fewer bacteria on the 3 wt%Cu and especially the 10 wt%Cu samples. Although the 10 wt%Cu alloy gave the best antibacterial results, it is desired that the Cu concentration is below similar to 3 wt%Cu to maintain similar mechanical and corrosive performance as CP-Ti. Therefore, it is proposed that future work focuses on the 3 wt%Cu alloy.

    Place, publisher, year, edition, pages
    ELSEVIER SCIENCE BV, 2019
    Keywords
    Copper, Titanium, Antibacterial, S. epidermidis, Ti2Cu
    National Category
    Metallurgy and Metallic Materials
    Identifiers
    urn:nbn:se:uu:diva-378615 (URN)10.1016/j.msec.2018.12.050 (DOI)000457952800069 ()30678959 (PubMedID)
    Available from: 2019-03-11 Created: 2019-03-11 Last updated: 2019-10-17Bibliographically approved
    3. Development of antibacterial Ti-Cux alloys for dental applications: effects of ageing for alloys with up to 10wt%Cu
    Open this publication in new window or tab >>Development of antibacterial Ti-Cux alloys for dental applications: effects of ageing for alloys with up to 10wt%Cu
    (English)Manuscript (preprint) (Other academic)
    Abstract [en]

    Peri-implantitis is a disease caused by bacteria, affecting dental implants in patients, who later require antibiotic treatments to avoid implant failure. This treatment has become more complicated recently due to growing antibiotic resistance. Titanium-copper alloys are a class of materials proposed to be appropriate as antibacterial biomaterials and have the potential to be a remedy against peri-implantitis and antibiotic resistance.

     

    The aim of this study was to investigate materials in the Ti-Cux class, exploring how Cu content (up to 10%) and ageing affect the material and antibacterial properties. The use of electron microscopy, X-ray diffraction, hardness testing, bacteriological culture and electrochemical testing were employed to characterize the materials.

    It was found that the alloys had two phases with Cu additions above 3 wt% and ageing increased the volume fraction of the Ti2Cu intermetallic compound. The hardness gradually increased with increased Cu additions, while ageing only affected the alloy with 10 wt%Cu dramatically (due to changes in microstructure). Ageing significantly decreased the corrosion rates of the Ti-Cux alloys. The aged 10wt%Cu alloy was the only alloy with an antibacterial effect after two hours, while after six hours bacteria killing occurred in all alloys with Cu additions above 5wt%.

     

    In conclusion, it was possible to tune the material and antibacterial properties of Ti-Cux alloys by %Cu addition and ageing steps, which makes further optimisation towards an antibacterial material promising.

     

    Keywords
    titanium alloys, copper, Ti2Cu, biomaterial, antibacterial
    National Category
    Medical Materials
    Identifiers
    urn:nbn:se:uu:diva-395300 (URN)
    Available from: 2019-10-16 Created: 2019-10-16 Last updated: 2019-10-17
    4. Investigation of copper alloying in a TNTZ-Cux alloy
    Open this publication in new window or tab >>Investigation of copper alloying in a TNTZ-Cux alloy
    2019 (English)In: MDPI Materials Biomaterials, ISSN 1996-1944Article in journal (Refereed) Submitted
    Abstract [en]

    Alloying titanium with copper has recently been investigated with the aim to develop an antibacterial alloy. However, due to the low strength of pure titanium, alloys such as Ti-Nb-Ta-Zr have been developed. In the present study, an existing Ti-1.6wt.%Nb-10wt.%Ta-1.7wt.%Zr (TNTZ) material – that was initially designed to have higher strength than grade 4 titanium and closer to that of Ti-6Al-4V - was alloyed with copper to investigate its effect on the microstructure, as a first step towards the development of a novel antibacterial material. 

    The initial design and modelling of the alloy system was performed using CALPHAD methods, to predict the phase transformations in the alloy. Following predictions, the alloys were produced using arc melting with appropriate heat treatments. The alloys were characterized using energy dispersive X-ray spectroscopy in scanning transmission electron microscopy (STEM-EDS) with transmission Kikuchi diffraction (TKD).

    The manufactured alloys had a three-phased crystal structure that was found in the alloys with 3wt.%Cu and higher, in line with the modelled alloy predictions. The phases included the α-Ti (HCP-Ti) with some Ta present in the crystal, Ti2Cu, and a bright phase with Ti, Cu and Ta in the crystal. The Ti2Cu crystals tended to precipitate in the grain boundaries of the α-Ti phase and bright phase. The hardness of the alloys increased with increased Cu addition, as did the presence of the Ti2Cu phase. Further studies to optimize the alloy could result in a suitable material for dental implants.

    Keywords
    Titanium alloy; microstructures; biomaterial, TNTZ
    National Category
    Medical Materials
    Identifiers
    urn:nbn:se:uu:diva-395278 (URN)
    Funder
    The Swedish Foundation for International Cooperation in Research and Higher Education (STINT), GA SA2017-7127
    Available from: 2019-10-16 Created: 2019-10-16 Last updated: 2019-10-17
  • 46.
    Fowler, Lee
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    Engqvist, Håkan
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    Norgren, Susanne
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    Öhman-Mägi, Caroline
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    Development of antibacterial Ti-Cux alloys for dental applications: effects of ageing for alloys with up to 10wt%CuManuscript (preprint) (Other academic)
    Abstract [en]

    Peri-implantitis is a disease caused by bacteria, affecting dental implants in patients, who later require antibiotic treatments to avoid implant failure. This treatment has become more complicated recently due to growing antibiotic resistance. Titanium-copper alloys are a class of materials proposed to be appropriate as antibacterial biomaterials and have the potential to be a remedy against peri-implantitis and antibiotic resistance.

     

    The aim of this study was to investigate materials in the Ti-Cux class, exploring how Cu content (up to 10%) and ageing affect the material and antibacterial properties. The use of electron microscopy, X-ray diffraction, hardness testing, bacteriological culture and electrochemical testing were employed to characterize the materials.

    It was found that the alloys had two phases with Cu additions above 3 wt% and ageing increased the volume fraction of the Ti2Cu intermetallic compound. The hardness gradually increased with increased Cu additions, while ageing only affected the alloy with 10 wt%Cu dramatically (due to changes in microstructure). Ageing significantly decreased the corrosion rates of the Ti-Cux alloys. The aged 10wt%Cu alloy was the only alloy with an antibacterial effect after two hours, while after six hours bacteria killing occurred in all alloys with Cu additions above 5wt%.

     

    In conclusion, it was possible to tune the material and antibacterial properties of Ti-Cux alloys by %Cu addition and ageing steps, which makes further optimisation towards an antibacterial material promising.

     

  • 47.
    Fowler, Lee
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    Engqvist, Håkan
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    Norgren, Susanne
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    Öhman-Mägi, Caroline
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    Investigation of copper alloying in a TNTZ-Cux alloy2019In: MDPI Materials Biomaterials, ISSN 1996-1944Article in journal (Refereed)
    Abstract [en]

    Alloying titanium with copper has recently been investigated with the aim to develop an antibacterial alloy. However, due to the low strength of pure titanium, alloys such as Ti-Nb-Ta-Zr have been developed. In the present study, an existing Ti-1.6wt.%Nb-10wt.%Ta-1.7wt.%Zr (TNTZ) material – that was initially designed to have higher strength than grade 4 titanium and closer to that of Ti-6Al-4V - was alloyed with copper to investigate its effect on the microstructure, as a first step towards the development of a novel antibacterial material. 

    The initial design and modelling of the alloy system was performed using CALPHAD methods, to predict the phase transformations in the alloy. Following predictions, the alloys were produced using arc melting with appropriate heat treatments. The alloys were characterized using energy dispersive X-ray spectroscopy in scanning transmission electron microscopy (STEM-EDS) with transmission Kikuchi diffraction (TKD).

    The manufactured alloys had a three-phased crystal structure that was found in the alloys with 3wt.%Cu and higher, in line with the modelled alloy predictions. The phases included the α-Ti (HCP-Ti) with some Ta present in the crystal, Ti2Cu, and a bright phase with Ti, Cu and Ta in the crystal. The Ti2Cu crystals tended to precipitate in the grain boundaries of the α-Ti phase and bright phase. The hardness of the alloys increased with increased Cu addition, as did the presence of the Ti2Cu phase. Further studies to optimize the alloy could result in a suitable material for dental implants.

  • 48.
    Fowler, Lee
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    Janson, Oscar
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    Norgren, Susanne
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    Engqvist, Håkan
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    Öhman-Mägi, Caroline
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    Titanium-Copper alloy as an antibacterial biomaterial2017In: Titanium-Copper alloy as an antibacterial biomaterial, 2017Conference paper (Refereed)
  • 49.
    Fu, Le
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    Andersson, Martin
    Unosson, Erik
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    Persson, Cecilia
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    Engqvist, Håkan
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    Xia, Wei
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    Influence of alkali metal additives on phase transition of translucent ZrO2/SiO2 glass ceramics prepared by a sol-gel method2015In: European Cells and Materials, ISSN 1473-2262, E-ISSN 1473-2262, Vol. 29, no S1, p. 10-Article in journal (Refereed)
  • 50.
    Fu, Le
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    Andersson, Martin
    Unosson, Erik
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    Persson, Cecilia
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    Engqvist, Håkan
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    Xia, Wei
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    Influences of alkali metals additives on phase transition of translucent ZrO2/SiO2 glass ceramic prepared by sol-gel method2015Conference paper (Refereed)
1234 1 - 50 of 186
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