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  • 1.
    Ajalloueian, Fatemeh
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - Ångström, Polymer Chemistry. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Zeiai, Said
    Fossum, Magdalena
    Hilborn, Jöns G.
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - Ångström, Polymer Chemistry. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Constructs of electrospun PLGA, compressed collagen and minced urothelium for minimally manipulated autologous bladder tissue expansion2014In: Biomaterials, ISSN 0142-9612, E-ISSN 1878-5905, Vol. 35, no 22, p. 5741-5748Article in journal (Refereed)
    Abstract [en]

    Bladder regeneration based on minced bladder mucosa in vivo expansion is an alternative to in vitro culturing of urothelial cells. Here, we present the design of a hybrid, electrospun poly(lactic-co-glycolide) (PLGA) - plastically compressed (PC) collagen scaffold that could allow in vivo bladder mucosa expansion. Optimisation of electrospinning was performed in order to obtain increased pore sizes and porosity to consolidate the construct and to support neovascularisation and tissue ingrowth. Tensile tests showed an increase in average tensile strength from 0.6 MPa for PC collagen to 3.57 MPa for the hybrid construct. The optimised PLGA support scaffold was placed between two collagen gels, and the minced tissue was distributed either on top or both on top and inside the construct prior to PC; this was then cultured for up to four weeks. Morphology, histology and SEM demonstrated that the construct maintained its integrity throughout cell culture. Cells from minced tissue migrated, expanded and re-organised to a confluent cell layer on the top of the construct after two weeks and formed a multilayered urothelium after four weeks. Cell morphology and phenotype was typical for urothelial mucosa during tissue culture. (C) 2014 Elsevier Ltd. All rights reserved.

  • 2.
    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
  • 3.
    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.

  • 4.
    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)
  • 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.
    The influence of porosity on the fatigue properties of brushite cement2016In: Biomaterials for tissue engineering models, 2016Conference 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.
    Compressive fatigue properties of a high-strength, degradable calcium phosphate bone cement – influence of porosity and environmentManuscript (preprint) (Other academic)
  • 7.
    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. 

  • 8.
    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)
  • 9.
    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. 

  • 10.
    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. 

  • 11.
    Allardyce, Benjamin J.
    et al.
    Deakin Univ, Inst Frontier Mat, Geelong, Vic, Australia..
    Rajkhowa, Rangam
    Deakin Univ, Inst Frontier Mat, Geelong, Vic, Australia..
    Dilley, Rodney J.
    Univ Western Australia, Sch Surg, Ear Sci Inst Australia, Nedlands, WA 6009, Australia.;Univ Western Australia, Sch Surg, Ear Sci Ctr, Nedlands, WA 6009, Australia..
    Xie, Zhigang
    Deakin Univ, Inst Frontier Mat, Geelong, Vic, Australia..
    Campbell, Luke
    Univ Melbourne, Dept Otolaryngol, Melbourne, Vic 3010, Australia..
    Keating, Adrian
    Univ Western Australia, Sch Mech & Chem Engn, Nedlands, WA 6009, Australia..
    Atlas, Marcus D.
    Univ Western Australia, Sch Surg, Ear Sci Inst Australia, Nedlands, WA 6009, Australia.;Univ Western Australia, Sch Surg, Ear Sci Ctr, Nedlands, WA 6009, Australia..
    von Unge, Magnus
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland. Akershus Univ Hosp, Dept ENT, Oslo, Norway.;Univ Oslo, Oslo, Norway..
    Wang, Xungai
    Deakin Univ, Inst Frontier Mat, Geelong, Vic, Australia..
    Comparative acoustic performance and mechanical properties of silk membranes for the repair of chronic tympanic membrane perforations2016In: Journal of The Mechanical Behavior of Biomedical Materials, ISSN 1751-6161, E-ISSN 1878-0180, Vol. 64, p. 65-74Article in journal (Refereed)
    Abstract [en]

    The acoustic and mechanical properties of silk membranes of different thicknesses were tested to determine their suitability as a repair material for tympanic membrane perforations. Membranes of different thickness (10-100 mu m) were tested to determine their frequency response and their resistance to pressure loads in a simulated ear canal model. Their mechanical rigidity to pressure loads was confirmed by tensile testing. These membranes were tested alongside animal cartilage, currently the strongest available myringoplasty graft as well as paper, which is commonly used for simpler procedures. Silk membranes showed resonant frequencies within the human hearing range and a higher vibrational amplitude than cartilage, suggesting that silk may offer good acoustic energy transfer characteristics. Silk membranes were also highly resistant to simulated pressure changes in the middle ear, suggesting they can resist retraction, a common cause of graft failure resulting from chronic negative pressures in the middle ear. Part of this strength can be explained by the substantially higher modulus of silk films compared with cartilage. This allows for the production of films that are much thinner than cartilage, with superior acoustic properties, but that still provide the same level of mechanical support as thicker cartilage. Together, these in vitro results suggest that silk membranes may provide good hearing outcomes while offering similar levels of mechanical support to the reconstructed middle ear.

  • 12.
    Andersson, Marlene
    et al.
    Department of Anatomy, Physiology and Biochemistry, Swedish University of Agricultural Sciences, Uppsala, Sweden..
    Jia, Qiupin
    Institute of Biological Sciences and Biotechnology, Donghua University, Shanghai, P.R. China..
    Abella, Ana
    ETSI de Caminos and Center for Biomedical Technology, Universidad Politécnica de Madrid, Madrid, Spain..
    Lee, Xiau-Yeen
    ETSI de Caminos and Center for Biomedical Technology, Universidad Politécnica de Madrid, Madrid, Spain..
    Landreh, Michael
    Department of Chemistry, Physical and Theoretical Chemistry Laboratory, University of Oxford, Oxford, UK..
    Purhonen, Pasi
    Department of Biosciences and Nutrition, Karolinska Institutet, Stockholm, Sweden.; School of Technology and Health, KTH Royal Institute of Technology, Stockholm, Sweden..
    Hebert, Hans
    Department of Biosciences and Nutrition, Karolinska Institutet, Stockholm, Sweden.; School of Technology and Health, KTH Royal Institute of Technology, Stockholm, Sweden..
    Tenje, Maria
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Microsystems Technology. Uppsala University, Science for Life Laboratory, SciLifeLab. Department of Biomedical Engineering, Lund University, Lund, Sweden..
    Robinson, Carol V.
    Department of Chemistry, Physical and Theoretical Chemistry Laboratory, University of Oxford, Oxford, UK..
    Meng, Qing
    Institute of Biological Sciences and Biotechnology, Donghua University, Shanghai, P.R. China..
    Plaza, Gustavo R.
    ETSI de Caminos and Center for Biomedical Technology, Universidad Politécnica de Madrid, Madrid, Spain..
    Johansson, Jan
    Department of Anatomy, Physiology and Biochemistry, Swedish University of Agricultural Sciences, Uppsala, Sweden.; Department of Neurobiology, Care Sciences and Society (NVS), Karolinska Institutet, Stockholm, Sweden.; Karolinska Institutet.
    Rising, Anna
    Department of Anatomy, Physiology and Biochemistry, Swedish University of Agricultural Sciences, Uppsala, Sweden.;Department of Neurobiology, Care Sciences and Society (NVS), Karolinska Institutet, Stockholm, Sweden.; Karolinska Institutet.
    Biomimetic spinning of artificial spider silk from a chimeric minispidroin2017In: Nature Chemical Biology, ISSN 1552-4450, E-ISSN 1552-4469, Vol. 13, no 3, p. 262-264Article in journal (Refereed)
    Abstract [en]

    Herein we present a chimeric recombinant spider silk protein (spidroin) whose aqueous solubility equals that of native spider silk dope and a spinning device that is based solely on aqueous buffers, shear forces and lowered pH. The process recapitulates the complex molecular mechanisms that dictate native spider silk spinning and is highly efficient; spidroin from one liter of bacterial shake-flask culture is enough to spin a kilometer of the hitherto toughest as-spun artificial spider silk fiber.

  • 13.
    Aulin, Cecilia
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Materials Chemistry.
    Extracellular Matrix Based Materials for Tissue Engineering2010Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    The extracellular matrix is (ECM) is a network of large, structural proteins and polysaccharides, important for cellular behavior, tissue development and maintenance. Present thesis describes work exploring ECM as scaffolds for tissue engineering by manipulating cells cultured in vitro or by influencing ECM expression in vivo. By culturing cells on polymer meshes under dynamic culture conditions, deposition of a complex ECM could be achieved, but with low yields. Since the major part of synthesized ECM diffused into the medium the rate limiting step of deposition was investigated. This quantitative analysis showed that the real rate limiting factor is the low proportion of new proteins which are deposited as functional ECM. It is suggested that cells are pre-embedded in for example collagen gels to increase the steric retention and hence functional deposition.

    The possibility to induce endogenous ECM formation and tissue regeneration by implantation of growth factors in a carrier material was investigated. Bone morphogenetic protein-2 (BMP-2) is a growth factor known to be involved in growth and differentiation of bone and cartilage tissue. The BMP-2 processing and secretion was examined in two cell systems representing endochondral (chondrocytes) and intramembranous (mesenchymal stem cells) bone formation. It was discovered that chondrocytes are more efficient in producing BMP-2 compared to MSC. The role of the antagonist noggin was also investigated and was found to affect the stability of BMP-2 and modulate its effect. Finally, an injectable gel of the ECM component hyaluronan has been evaluated as delivery vehicle in cartilage regeneration. The hyaluronan hydrogel system showed promising results as a versatile biomaterial for cartilage regeneration, could easily be placed intraarticulary and can be used for both cell based and cell free therapies.

    List of papers
    1. Extracellular matrix-polymer hybrid materials produced in a pulsed-flow bioreactor system
    Open this publication in new window or tab >>Extracellular matrix-polymer hybrid materials produced in a pulsed-flow bioreactor system
    2009 (English)In: Journal of Tissue Engineering and Regenerative Medicine, ISSN 1932-6254, Vol. 3, no 3, p. 188-195Article in journal (Refereed) Published
    Abstract [en]

    Cell adhesion, interaction with material, cell proliferation and the production of an extracellular matrix (ECM) are all important factors determining the successful performance of an engineered scaffold. Scaffold design should aim at creating structures which can guide cells into forming new, functional tissue. In this study, the concept of in situ deposition of ECM by human dermal fibroblasts onto a compliant, knitted poly (ethyleneterephtalate) support is demonstrated, creating in vitro produced ECM polymer hybrid materials for tissue engineering. Comparison of cells cultured under static and dynamic conditions were examined, and the structure and morphology of the materials so formed were evaluated, along with the amount collagen deposited by the seeded cells. In vitro produced ECM polymer hybrid scaffolds could be created in this way, with the dynamic culture conditions increasing ECM deposition. Histological analysis indicated a homogenous distribution of cells in the 1 mm thick scaffold, surrounded by a matrix-like structure. ECM deposition was observed throughout the materials wigh 81.6 µg/cm2 of collagen deposited after 6 weeks. Cell produced bundles of ECM fibres bridged the polymer filaments and anchored cells to the support. These findings open hereto unknown possibilities of producing materials with structure designed by engineering together with biochemical composition given by cells.

    Place, publisher, year, edition, pages
    John Wiley & Sons, Ltd, 2009
    Keywords
    extracellular matrix, scaffold, polymer support, fibroblasts, bioreactor, dynamic culture conditions
    National Category
    Chemical Sciences
    Research subject
    Inorganic Chemistry
    Identifiers
    urn:nbn:se:uu:diva-106096 (URN)10.1002/term.152 (DOI)000265268400003 ()
    Available from: 2009-06-15 Created: 2009-06-15 Last updated: 2010-08-02Bibliographically approved
    2. Bulk collagen incorporation rates into knitted stiff fibre polymer in tissue-engineered scaffolds: the rate-limiting step
    Open this publication in new window or tab >>Bulk collagen incorporation rates into knitted stiff fibre polymer in tissue-engineered scaffolds: the rate-limiting step
    Show others...
    2008 (English)In: Journal of Tissue Engineering and Regenerative Medicine, ISSN 1932-6254, Vol. 2, no 8, p. 507-514Article in journal (Refereed) Published
    Abstract [en]

    Fabrication of tissue-engineered constructs in vitro relies on sufficient synthesis of extracellular matrix (ECM) by cells to form a material suitable for normal function in vivo. Collagen synthesis by human dermal fibroblasts grown in vitro on two polymers, polyethylene terephthalate (PET) and polyglycolic acid (PGA), was measured by high-performance liquid chromatography (HPLC). Cells were either cultured in a dynamic environment, where meshes were loaded onto a pulsing tube in a bioreactor, or in a static environment without pulsing. Collagen synthesis by cells cultured on a static mesh increased by six-fold compared to monolayer culture, and increased by up to a further 5.4-fold in a pulsed bioreactor. However, little of the collagen synthesized was deposited onto the meshes, almost all being lost to the medium. The amount of collagen deposited onto meshes was highest when cells were cultured dynamically on PET meshes (17.6 µg), but deposition still represented only 1.4% of the total synthesized. Although total collagen synthesis was increased by the use of 3D culture and the introduction of pulsing, the results suggest that the limiting factor for fabrication of a tissue-engineered construct within practical timescales is not the amount of collagen synthesized but the quantity retained (i.e. deposited) within the construct during culture. This may be enhanced by systems which promote or assemble true 3D multi-layers of cells.

    Place, publisher, year, edition, pages
    John Wiley & Sons, Ltd., 2008
    Keywords
    collagen synthesis, collagen deposition, tissue engineering, polyethylene terephthalate, 3D culture, bioreactors
    National Category
    Chemical Sciences
    Research subject
    Inorganic Chemistry
    Identifiers
    urn:nbn:se:uu:diva-99347 (URN)10.1002/term.126 (DOI)000262272900007 ()
    Available from: 2009-03-12 Created: 2009-03-12 Last updated: 2010-08-04Bibliographically approved
    3. Comparative studies on BMP-2 processing and secretion in chondrocytes and mesenchymal cells and the effect of noggin
    Open this publication in new window or tab >>Comparative studies on BMP-2 processing and secretion in chondrocytes and mesenchymal cells and the effect of noggin
    (English)Manuscript (preprint) (Other academic)
    Keywords
    bone formation, BMP-2, noggin, chondrocytes, mesenchymal stem cells
    Identifiers
    urn:nbn:se:uu:diva-110746 (URN)
    Available from: 2009-11-24 Created: 2009-11-24
    4. Evaluation of an injectable hyaluronan hydrogel for cartilage regeneration
    Open this publication in new window or tab >>Evaluation of an injectable hyaluronan hydrogel for cartilage regeneration
    Show others...
    (English)Manuscript (preprint) (Other academic)
    Keywords
    hyaluronan, chondrocytes, mesenchymal stem cells, cartilage, injectable, bone morphogenetic protein-2, rabbit model
    Identifiers
    urn:nbn:se:uu:diva-110750 (URN)
    Available from: 2009-11-24 Created: 2009-11-24
  • 14.
    Ballo, Ahmed
    et al.
    Gothenburg University.
    Omar, Omar
    Gothenburg Univerity.
    Xia, Wei
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    Palmquist, Anders
    Gothenburg University.
    Dental Implant Surfaces Implant Dentistry - A Rapidly Evolving Practic: Physicochemical Properties, Biological Performance, and Trends2011In: Implant Dentistry: A Rapidly Evolving Practice / [ed] Ilser Turkyilmaz, INTECH , 2011Chapter in book (Refereed)
  • 15.
    Berts, Ida
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - Ångström. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Ossipov, Dmitri
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - Ångström. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Fragneto, Giovanna
    Institut Laue-Langevin.
    Frisk, Andreas
    Uppsala University, Disciplinary Domain of Science and Technology, Physics, Department of Physics and Astronomy, Materials Physics.
    Rennie, Adrian. R
    Uppsala University, Disciplinary Domain of Science and Technology, Physics, Department of Physics and Astronomy, Materials Physics.
    Polymeric Smart Coating Strategy for Titanium Implants2014In: Advanced Engineering Materials, ISSN 1438-1656, E-ISSN 1527-2648, Vol. 16, no 11, p. 1340-1350Article in journal (Refereed)
    Abstract [en]

    Hyaluronan based hydrogel coatings can mimic extracellular matrix components and incorporate growth factors that can be released during a progressive degradation while new tissue regenerates. This paper describes a structural characterization of a hydrogel coating made of modified hyaluronan polymers and how these coatings interact with bone morphogenetic protein-2 (BMP-2). Quartz crystal microbalance and neutron reflectivity measurements were used for in-situ, real-time measurements of the adsorption properties of polymers and proteins on smooth titanium oxide surfaces that mimic implant products in orthopedics. The adsorption of BMP-2 on a bare titanium oxide surface is compared to that on titanium oxide coated with different chemically modified hyaluronan, the most important being hyaluronan with bisphosphonate groups (HA-BP). The subsequent release of the BMP-2 from these hydrogel coatings could be triggered by calcium ions. The amount of adsorbed protein on the surfaces as well as the amount of released protein both depend on the type of hyaluronan coating. We conclude that HA-BP coated titanium oxide surfaces provide an excellent material for growth factor delivery in-vivo.

  • 16.
    Bou-Francis, Antony
    et al.
    School of Mechanical Engineering, University of Leeds, UK.
    Lopez, Alejandro
    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.
    Hall, Richard M.
    School of Mechanical Engineering, University of Leeds, UK.
    Kapur, Nikil
    School of Mechanical Engineering, University of Leeds, UK.
    Assessing cement injection behaviour in cancellous bone: An in vitro study using flow models2014In: Journal of biomaterials applications, ISSN 0885-3282, E-ISSN 1530-8022, Vol. 29, no 4, p. 582-594Article in journal (Refereed)
    Abstract [en]

    Understanding the cement injection behaviour during vertebroplasty and accurately predicting the cement placement within the vertebral body is extremely challenging. As there is no standardized methodology, we propose a novel method using reproducible and pathologically representative flow models to study the influence of cement properties on injection behaviour. The models, confined between an upper glass window and a lower aluminium plate, were filled with bone marrow substitute and then injected (4, 6 and 8min after cement mixing) with commercially available bone cements (SimplexP, Opacity+, OsteopalV and Parallax) at a constant flow rate (3mL/min). A load cell was used to measure the force applied on the syringe plunger and calculate the peak pressure. A camera was used to monitor the cement flow during injection and calculate the following parameters when the cement had reached the boundary of the models: the time to reach the boundary, the filled area and the roundness. The peak pressure was comparable to that reported during clinical vertebroplasty and showed a similar increase with injection time. The study highlighted the influence of cement formulations and model structure on the injection behaviour and showed that cements with similar composition/particle size had similar flow behaviour, while the introduction of defects reduced the time to reach the boundary, the filled area and the roundness. The proposed method provides a novel tool for quick, robust differentiation between various cement formulations through the visualization and quantitative analysis of the cement spreading at various time intervals.

  • 17.
    Cai, Bing
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    Ceramic Materials for Administration of Potent Drugs2015Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    This thesis aimed to investigate and document the potential of applying ceramics in two specific drug delivery applications: tamper-resistant opioid formulations and transdermal enhancement protrusions.

    Geopolymers were developed into the matrix for a tamper-resistant formulation, aiming to protect drug substances from non-medical abuse. The synthesis conditions and excipients composition of the geopolymer-based formulation were modified in this work to facilitate a stable and extended drug delivery. Results showed that 37ºC 100% humidity for 48 hours were applicable conditions to obtain geopolymer with suitable mechanical strength and porosity. Moreover, it was found that the integration of poly(methyl acrylate) into the geopolymer-based formulation could reduce the drug release at low pH and, meanwhile, maintain the mechanical strength. Therefore, the geopolymer-based drug formulations concluded from these studies were applied in oral and transdermal delivery systems. Evidence of the tamper-resistance of geopolymer-based oral and transdermal formulations was documented and compared to the corresponding commercial opioid formulations. The results provided experimental support for the positive effects of geopolymers as drug carriers for the tamper-resistance of oral and transdermal delivery systems.

    Self-setting bioceramics, calcium phosphate and calcium sulfate were fabricated into transdermal enhancement protrusions in this work for the first time. Results showed that, under mild conditions, both bioceramics could form pyramid-shaped needles in the micron size. The drug release from these needles could be controlled by the bulk surface area, porosity and degradation of the bioceramics. An in vitro insertion test showed that the bioceramic microneedles had enough mechanical strength to insert into skin. Further optimization on the geometry of needles and the substrate material was also performed. The higher aspect-ratio needles with a flexible and self-swellable substrate could release most of the drug content within 4 hours and could penetrate through the stratum corneum by manual insertion. This study explored the potential application of bioceramics in transdermal enhancement protrusions and showed promising indication of their future developments.

    List of papers
    1. 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
    2. Polymer excipients enable sustained drug release in low pH from mechanically strong inorganic geopolymers
    Open this publication in new window or tab >>Polymer excipients enable sustained drug release in low pH from mechanically strong inorganic geopolymers
    Show others...
    2012 (English)In: Results in Pharma Sciences, ISSN 2211-2863, Vol. 2, p. 23-28Article in journal (Refereed) Published
    Place, publisher, year, edition, pages
    Elsevier, 2012
    National Category
    Pharmaceutical Sciences Engineering and Technology
    Identifiers
    urn:nbn:se:uu:diva-161811 (URN)10.1016/j.rinphs.2012.02.001 (DOI)
    Available from: 2011-11-17 Created: 2011-11-17 Last updated: 2018-11-05
    3. 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
    4. Development and evaluation of a tampering resistant transdermal fentanyl patch
    Open this publication in new window or tab >>Development and evaluation of a tampering resistant transdermal fentanyl patch
    2015 (English)In: International Journal of Pharmaceutics, ISSN 0378-5173, E-ISSN 1873-3476, Vol. 488, no 1-2, p. 102-107Article in journal (Refereed) Published
    Keywords
    Transdermal patch, Tamper-resistance, Geopolymer, Fentanyl, Abuse, Drug delivery
    National Category
    Ceramics Substance Abuse
    Identifiers
    urn:nbn:se:uu:diva-245029 (URN)10.1016/j.ijpharm.2015.04.061 (DOI)000355887100013 ()25913120 (PubMedID)
    Available from: 2015-02-24 Created: 2015-02-24 Last updated: 2018-02-08Bibliographically approved
    5. Self-setting bioceramic microscopic protrusions for transdermal drug delivery
    Open this publication in new window or tab >>Self-setting bioceramic microscopic protrusions for transdermal drug delivery
    2014 (English)In: Journal of materials chemistry. B, ISSN 2050-750X, E-ISSN 2050-7518, Vol. 2, no 36, p. 5992-5998Article in journal (Refereed) Published
    Abstract [en]

    Microneedle (MN) technology offers both an efficient and a minimally invasive transdermal drug delivery strategy. The current MNs, made of silicon and metal, have poor biocompatibility and low drug loading, while the polymer MNs have some constraints related to mechanical strength and storage conditions. In this study, self-setting bioceramics were explored as substitutes for the current MN materials for the first time. Self-setting bioceramic microneedles were fabricated using a master mold by a procedure under mild conditions, which could minimize the drug degradation during fabrication and also facilitates a higher drug loading capability than the other current ceramic microneedles. The drug release and mechanical strength were correlated with the microstructure and porosity of the needles. As observed by SEM and microCT, the ceramic paste could fully fill the geometry of the mould and was cured into an array of micro-sized needles. The drug release study showed that the release rate from this type of MN array could be controlled by the bulk surface area, porosity and resorption rate of the ceramic needles. Applying the MNs to porcine skin indicated that the needles were able to pierce the stratum corneum of the skin. We successfully prepared the bioceramic needles that have high mechanical strength and are resorbable, which can promote safe, efficient and successful transdermal drug delivery.

    National Category
    Bio Materials Engineering and Technology
    Research subject
    Engineering Science with specialization in Materials Science
    Identifiers
    urn:nbn:se:uu:diva-233125 (URN)10.1039/c4tb00764f (DOI)000341300300007 ()
    Conference
    microneedles 2014, Baltimore, May 19-21, 2014
    Available from: 2014-09-29 Created: 2014-09-29 Last updated: 2018-02-08
    6. Bioceramic microneedles with flexible and self-swelling substrate
    Open this publication in new window or tab >>Bioceramic microneedles with flexible and self-swelling substrate
    (English)Article in journal (Other academic) Submitted
    Keywords
    Microneedles; Bioceramics; Controlled-release; Skin penetration; Clonidine
    National Category
    Biomaterials Science Ceramics
    Identifiers
    urn:nbn:se:uu:diva-246404 (URN)
    Available from: 2015-03-06 Created: 2015-03-06 Last updated: 2018-02-08
  • 18.
    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.
    Aluminum release from geopolymer-based opioid formulation2014Conference paper (Refereed)
  • 19.
    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 effect of polymer content on drug release and mechanical strength of a geopolymer ER formulation for opioid drugs2014Conference paper (Refereed)
  • 20.
    Cai, Bing
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    Söderkvist, Karin
    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.
    A new screening in-vitro method to study drug release in early development of transdermal drug delivery systems2012In: European Cells and Materials, ISSN 1473-2262, E-ISSN 1473-2262, Vol. 23, no Suppl. 5, p. 22-Article in journal (Refereed)
  • 21.
    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.
    Engqvist, Håkan
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    Development and evaluation of self-setting bioceramic microneedles2014Conference paper (Refereed)
  • 22.
    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.

  • 23.
    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.
    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.
    Bioceramic microneedles with flexible and self-swelling substrateArticle in journal (Other academic)
  • 24.
    Cai, Yanling
    et al.
    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.
    Melhus, Åsa
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Microbiology and Infectious Medicine, Clinical Bacteriology.
    Engqvist, Håkan
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    Welch, Ken
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Nanotechnology and Functional Materials.
    Photocatalytic inactivation of biofilms on bioactive dental adhesives2014In: Journal of Biomedical Materials Research. Part B - Applied biomaterials, ISSN 1552-4973, E-ISSN 1552-4981, Vol. 102, no 1, p. 62-67Article in journal (Refereed)
    Abstract [en]

    Biofilms are the most prevalent mode of microbial life in nature and are 10-1000 times more resistant to antibiotics than planktonic bacteria. Persistent biofilm growth associated at the margin of a dental restoration often leads to secondary caries, which remains a challenge in restorative dentistry. In this work, we present the first in vitro evaluation of on-demand photocatalytic inactivation of biofilm on a novel dental adhesive containing TiO2 nanoparticles. Streptococcus mutans biofilm was cultured on this photocatalytic surface for 16 h before photocatalytic treatment with ultraviolet-A (UV-A) light. UV-A doses ranging from 3 to 43 J/cm(2) were applied to the surface and the resulting viability of biofilms was evaluated with a metabolic activity assay incorporating phenol red that provided a quantitative measure of the reduction in viability due to the photocatalytic treatments. We show that an UV-A irradiation dose of 8.4 J/cm(2) leads to one order of magnitude reduction in the number of biofilm bacteria on the surface of the dental adhesives while as much as 5-6 orders of magnitude reduction in the corresponding number can be achieved with a dose of 43 J/cm(2). This material maintains its functional properties as an adhesive in restorative dentistry while offering the possibility of a novel dental procedure in the treatment or prevention of bacterial infections via on-demand UV-A irradiation. Similar materials could be developed for the treatment of additional indications such as peri-implantits.

  • 25.
    Cai, Yanling
    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.
    Welch, Ken
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Nanotechnology and Functional Materials.
    Bacteria viability assessment after photocatalytic treatment2014In: 3 Biotech, ISSN 2190-5738, E-ISSN 2190-5738, Vol. 4, no 2, p. 149-157Article in journal (Refereed)
    Abstract [en]

    The aim of the present work was to evaluate several methods for analyzing the viability of bacteria after antibacterial photocatalytic treatment. Colony-forming unit (CFU) counting, metabolic activity assays based on resazurin and phenol red and the Live/Dead® BacLight™ bacterial viability assay (Live/Dead staining) were employed to assess photocatalytically treated Staphylococcus epidermidis and Streptococcus mutans. The results showed conformity between CFU counting and the metabolic activity assays, while Live/Dead staining showed a significantly higher viability post-treatment. This indicates that the Live/Dead staining test may not be suitable for assessing bacterial viability after photocatalytic treatment and that, in general, care should be taken when selecting a method for determining the viability of bacteria subjected to photocatalysis. The present findings are expected to become valuable for the development and evaluation of photocatalytically based disinfection applications

  • 26.
    Cardemil, Carina
    et al.
    University of Gothenburg.
    Elgali, Ibrahim
    University of Gothenburg.
    Xia, Wei
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    Emanuelsson, Lena
    Gothenburg University.
    Norlindh, Birgitta
    University of Gothenburg.
    Omar, Omar
    University of Gothenburg.
    Thomsen, Peter
    Gothenburg University.
    Strontium-Doped Calcium Phosphate and Hydroxyapatite Granules Promote Different Inflammatory and Bone Remodelling Responses in Normal and Ovariectomised Rats2013In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 8, no 12, p. e84932-Article in journal (Refereed)
    Abstract [en]

    The healing of bone defects may be hindered by systemic conditions such as osteoporosis. Calcium phosphates, with or without ion substitutions, may provide advantages for bone augmentation. However, the mechanism of bone formation with these materials is unclear. The aim of this study was to evaluate the healing process in bone defects implanted with hydroxyapatite (HA) or strontium-doped calcium phosphate (SCP) granules, in non-ovariectomised (non-OVX) and ovariectomised (OVX) rats. After 0 (baseline), six and 28d, bone samples were harvested for gene expression analysis, histology and histomorphometry. Tumour necrosis factor-alpha (TNF-alpha), at six days, was higher in the HA, in non-OVX and OVX, whereas interleukin-6 (IL-6), at six and 28d, was higher in SCP, but only in non-OVX. Both materials produced a similar expression of the receptor activator of nuclear factor kappa-B ligand (RANKL). Higher expression of osteoclastic markers, calcitonin receptor (CR) and cathepsin K (CatK), were detected in the HA group, irrespective of non-OVX or OVX. The overall bone formation was comparable between HA and SCP, but with topological differences. The bone area was higher in the defect centre of the HA group, mainly in the OVX, and in the defect periphery of the SCP group, in both non-OVX and OVX. It is concluded that HA and SCP granules result in comparable bone formation in trabecular bone defects. As judged by gene expression and histological analyses, the two materials induced different inflammatory and bone remodelling responses. The modulatory effects are associated with differences in the spatial distribution of the newly formed bone.

  • 27.
    Chen, Song
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    Glass Ionomer Cements with Improved Bioactive and Antibacterial Properties2016Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Dental restorative cements are placed in a harsh oral environment where they are subjected to thermal shock, chemical degradation, and repeating masticatory force. The ideal restorative dental cements should have superior mechanical properties, chemical stability, aesthetic, good handling properties, biocompatibility, antibacterial properties, and preferably bioactivity. This thesis presents research on dental restorative cements with enhanced properties. The overall aim was to increase the bioactivity and antibacterial properties of dental restorative cements without affecting their other properties.

    The effect from adding calcium silicate to glass ionomer cement (GIC) was investigated. The results showed that calcium silicate could increase the bioactivity and reduce the cytotoxicity of conventional glass ionomer cement without compromising its setting and mechanical properties.

    Hydroxyapatite (HA) with a high aspect ratio and thin nacreous-layered monetite sheets were also synthesized. Nano HA particles with an aspect ratio of 50 can be synthesized by both precipitation and hydrothermal methods. The aspect ratio was controlled via the pH of reaction medium. Thin nacreous-layered monetite sheets were synthesized through a self-assembly process in the presence of an amine based cationic quaternary surfactant. Temperature, pH, and presence of surfactant played essential roles in forming the nacreous-layered monetite sheets. Then the effect from adding silver doped HA and monetite particles was investigated. The results showed that the antibacterial properties of GIC could be increased by incorporating silver doped HA and monetite particles. Further examination showed that the pH change, F- ion release, and concentration of released Ag+ ions were not responsible for the improved antibacterial properties.

    The quasi-static strengths and compressive fatigue limits of four types of the most commonly used dental restorations were evaluated. In our study, resin modified GIC and resin-based composite showed superior static compressive strength and fatigue limits compared to conventional GIC. The static compressive strength of dental cements increased with the aging time. However, aging had no effect on the compressive fatigue limit of resin modified GIC and resin-based composite. The compressive fatigue limit of conventional GIC even showed a drastic decrease after aging.

    List of papers
    1. Enhanced bioactivity of glass ionomer cement by incorporating calcium silicates
    Open this publication in new window or tab >>Enhanced bioactivity of glass ionomer cement by incorporating calcium silicates
    2016 (English)In: Biomatter, ISSN 2159-2527, E-ISSN 2159-2535, Vol. 6, no 1, p. e1123842-1-e1123842-13Article in journal (Refereed) Published
    National Category
    Materials Engineering
    Identifiers
    urn:nbn:se:uu:diva-281936 (URN)
    External cooperation:
    Available from: 2016-03-31 Created: 2016-03-31 Last updated: 2018-02-08
    2. Cytotoxicity of modified glass ionomer cement on odontoblast cells
    Open this publication in new window or tab >>Cytotoxicity of modified glass ionomer cement on odontoblast cells
    Show others...
    2016 (English)In: Journal of materials science. Materials in medicine, ISSN 0957-4530, E-ISSN 1573-4838, Vol. 27, no 7, article id 116Article in journal (Refereed) Published
    Abstract [en]

    Recently a modified glass ionomer cement (GIC) with enhanced bioactivity due to the incorporation of wollastonite or mineral trioxide aggregate (MTA) has been reported. The aim of this study was to evaluate the cytotoxic effect of the modified GIC on odontoblast-like cells. The cytotoxicity of a conventional GIC, wollastonite modified GIC (W-mGIC), MTA modified GIC (M-mGIC) and MTA cement has been evaluated using cement extracts, a culture media modified by the cement. Ion concentration and pH of each material in the culture media were measured and correlated to the results of the cytotoxicity study. Among the four groups, conventional GIC showed the most cytotoxicity effect, followed by W-mGIC and M-mGIC. MTA showed the least toxic effect. GIC showed the lowest pH (6.36) while MTA showed the highest (8.62). In terms of ion concentration, MTA showed the largest Ca2+ concentration (467.3 mg/L) while GIC showed the highest concentration of Si4+ (19.9 mg/L), Al3+ (7.2 mg/L) and Sr2+ (100.3 mg/L). Concentration of F- was under the detection limit (0.02 mg/L) for all samples. However the concentrations of these ions are considered too low to be toxic. Our study showed that the cytotoxicity of conventional GIC can be moderated by incorporating calcium silicate based ceramics. The modified GIC might be promising as novel dental restorative cements.

    National Category
    Cell Biology Materials Chemistry Engineering and Technology
    Identifiers
    urn:nbn:se:uu:diva-297514 (URN)10.1007/s10856-016-5729-y (DOI)000379031200002 ()27221819 (PubMedID)
    Funder
    Swedish Research Council, 2013-5419 2011-3399EU, FP7, Seventh Framework ProgrammeVINNOVALars Hierta Memorial Foundation, FO2014-0334
    Available from: 2016-06-23 Created: 2016-06-23 Last updated: 2018-02-08Bibliographically approved
    3. Compressive fatigue limit of four types of dental restorative materials
    Open this publication in new window or tab >>Compressive fatigue limit of four types of dental restorative materials
    Show others...
    2016 (English)In: Journal of The Mechanical Behavior of Biomedical Materials, ISSN 1751-6161, E-ISSN 1878-0180, Vol. 61, p. 283-289Article in journal (Refereed) Published
    Abstract [en]

    The purpose of this study was to evaluate the quasi-static compressive strength and the compressive fatigue limit of four different dental restorative materials, before and after aging in distilled water for 30 days. A conventional glass ionomer cement (Fuji IX GP; IG), a zinc-reinforced glass ionomer cement (Chemfil rock; CF), a light curable resin-reinforced glass ionomer cement (Fuji II LC; LC) and a resin-based composite (Quixfil; QF) were investigated. Cylindrical specimens (4 mm in diameter and 6 mm in height) were prepared according to the manufacturer's instructions. The compressive fatigue limit was obtained using the staircase method. Samples were tested in distilled water at 37 degrees C, at a frequency of 10 Hz with 10(5) cycles set as run-out. 17 fatigue samples were tested for each group. Two-way ANOVA and one-way ANOVA followed by Tukey's post-hoc test were used to analyze the results. Among the four types of materials, the resin-based composite exhibited the highest compressive strength (244 +/- 13.0 MPa) and compressive fatigue limit (134 +/- 7.8 MPa), followed by the light-cured resin reinforced glass ionomer cement (168 +/- 8.5 MPa and 92 +/- 6.6 MPa, respectively) after one day of storage in distilled water. After being stored for 30 days, all specimens showed an increase in compressive strength. Aging showed no effect on the compressive fatigue limit of the resin-based composite and the light-cured resin reinforced glass ionomer cement, however, the conventional glass ionomer cements showed a drastic decrease (37% for IG, 31% for CF) in compressive fatigue limit. In conclusion, in the present study, resin modified GIC and resin-based composite were found to have superior mechanical properties to conventional GIC.

    Keywords
    Dental restorative materials; Fatigue; Aging; Compressive
    National Category
    Materials Engineering
    Identifiers
    urn:nbn:se:uu:diva-281942 (URN)10.1016/j.jmbbm.2016.03.031 (DOI)000380080400026 ()27085845 (PubMedID)
    Available from: 2016-03-31 Created: 2016-03-31 Last updated: 2018-02-08Bibliographically approved
    4. Highly repeatable synthesis of nHA with high aspect ratio
    Open this publication in new window or tab >>Highly repeatable synthesis of nHA with high aspect ratio
    Show others...
    2015 (English)In: Materials letters (General ed.), ISSN 0167-577X, E-ISSN 1873-4979, Vol. 159, p. 163-167Article in journal (Refereed) Published
    National Category
    Biomaterials Science Engineering and Technology
    Identifiers
    urn:nbn:se:uu:diva-265712 (URN)10.1016/j.matlet.2015.06.086 (DOI)000362603000043 ()
    Funder
    Swedish Research Council, 2013-5419VINNOVA, 2010-01907EU, FP7, Seventh Framework Programme, INFRA-2010-262163
    Available from: 2015-11-02 Created: 2015-11-02 Last updated: 2018-02-08
    5. Synthesis of calcium phosphate crystals with thin nacreous structure
    Open this publication in new window or tab >>Synthesis of calcium phosphate crystals with thin nacreous structure
    Show others...
    2016 (English)In: CrystEngComm, ISSN 1466-8033, E-ISSN 1466-8033, Vol. 18, no 6, p. 1064-1069Article in journal (Refereed) Published
    Abstract [en]

    Nacre-like structures have attracted great interest in recent years due to their outstanding toughness, stiffness and impact resistance. However, there is a challenge associated with engineering nacre-like calcium phosphate crystals. In this study, thin nacreous-like monetite sheets were synthesized in solutions guided by a surfactant. The influence of temperature, initial pH, Ca/P ratio, stirring time and the concentration of cetyltrimethylammonium bromide (CTAB) on the nacre-like structure has been studied. Findings showed that a nacre-like structure could only be formed at a high temperature (90 degrees C), high initial pH (11), sufficient stirring time (3 h), and under the presence of CTAB. A small-angle X-ray scattering experiment carried out at a synchrotron radiation facility showed that the distance between nanolayers was around 2.6 nm and TEM confirmed the fine sheet-like structure. The mechanism of the formation the nacre-like structure and its characterization were discussed.

    National Category
    Bio Materials
    Identifiers
    urn:nbn:se:uu:diva-274987 (URN)10.1039/c5ce02078f (DOI)000369609800025 ()
    Funder
    Swedish Research Council, 2013-5419Knut and Alice Wallenberg Foundation
    Available from: 2016-01-27 Created: 2016-01-27 Last updated: 2018-02-08Bibliographically approved
    6. Synthesis of Ag doped calcium phosphate particles and their antibacterial effect as additives in dental glass ionomer cements
    Open this publication in new window or tab >>Synthesis of Ag doped calcium phosphate particles and their antibacterial effect as additives in dental glass ionomer cements
    2016 (English)In: Journal of materials science. Materials in medicine, ISSN 0957-4530, E-ISSN 1573-4838, Vol. 27, no 11, article id 172Article in journal (Refereed) Published
    Abstract [en]

    Developing dental restorations with enhanced antibacterial properties has been a constant quest for materials scientists. The aim of this study was to synthesize silver doped calcium phosphate particles and use them to improve antibacterial properties of conventional glass ionomer cement. The Ag doped monetite (Ag-DCPA) and hydroxyapatite (Ag-HA) were synthesized by precipitation method and characterized using X-ray diffraction, scanning electron microscope and X-ray fluorescence spectroscopy. The antibacterial properties of the cements aged for 1 day and 7 days were evaluated by direct contact measurement using staphylococcus epidermis Xen 43. Ion concentrations (F- and Ag+) and pH were measured to correlate to the results of the antibacterial study. The compressive strength of the cements was evaluated with a crosshead speed of 1 mm/min. The glass ionomer cements containing silver doped hydroxyapatite or monetite showed improved antibacterial properties. Addition of silver doped hydroxyapatite or monetite did not change the pH and ion release of F-. Concentration of Ag+ was under the detection limit (0.001 mg/L) for all samples. Silver doped hydroxyapatite or monetite had no effect on the compressive strength of glass ionomer cement.

    National Category
    Ceramics
    Identifiers
    urn:nbn:se:uu:diva-301918 (URN)10.1007/s10856-016-5785-3 (DOI)000386564000001 ()27704376 (PubMedID)
    Available from: 2016-08-25 Created: 2016-08-25 Last updated: 2018-02-08Bibliographically approved
  • 28.
    Chen, Song
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    Pujari-Palmer, Shiuli
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    Rubino, Stefano
    Univ Oslo, Dept Phys, Oslo, Norway; Simon Fraser Univ, Dept Chem, Burnaby, BC V5A 1S6, Canada.
    Westlund, Viktoria
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    Ott, Marjam
    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.
    Highly repeatable synthesis of nHA with high aspect ratio2015In: Materials letters (General ed.), ISSN 0167-577X, E-ISSN 1873-4979, Vol. 159, p. 163-167Article in journal (Refereed)
  • 29.
    Dancila, Dragos
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Solid State Electronics.
    Augustine, Robin
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Solid State Electronics.
    Töpfer, Fritzi
    KTH Royal Inst Technol, Stockholm, Sweden.
    Dudorov, Sergey
    KTH Royal Inst Technol, Stockholm, Sweden.
    Hu, Xin
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Solid State Electronics.
    Emtestam, Lennart
    Karolinska Inst, Div Dermatol & Venereol, Stockholm, Sweden.
    Tenerz, Lars
    Optiga AB, Uppsala, Sweden.
    Oberhammer, Jachim
    KTH Royal Inst Technol, Stockholm, Sweden.
    Rydberg, Anders
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Solid State Electronics.
    Millimeter wave silicon micromachined waveguide probe as an aid for skin diagnosis - results of measurements on phantom material with varied water content2014In: Skin research and technology, ISSN 0909-752X, E-ISSN 1600-0846, Vol. 20, no 1, p. 116-123Article in journal (Refereed)
    Abstract [en]

    Background

    More than 2 million cases of skin cancer are diagnosed annually in the United States, which makes it the most common form of cancer in that country. Early detection of cancer usually results in less extensive treatment and better outcome for the patient. Millimeter wave silicon micromachined waveguide probe is foreseen as an aid for skin diagnosis, which is currently based on visual inspection followed by biopsy, in cases where the macroscopical picture raises suspicion of malignancy.

    Aims

    Demonstration of the discrimination potential of tissues of different water content using a novel micromachined silicon waveguide probe. Secondarily, the silicon probe miniaturization till an inspection area of 600 x 200 m2, representing a drastic reduction by 96.3% of the probing area, in comparison with a conventional WR-10 waveguide. The high planar resolution is required for histology and early-state skin-cancer detection.

    Material and methods

    To evaluate the probe three phantoms with different water contents, i.e. 50%, 75% and 95%, mimicking dielectric properties of human skin were characterized in the frequency range of 95-105GHz. The complex permittivity values of the skin are obtained from the variation in frequency and amplitude of the reflection coefficient (S11), measured with a Vector Network Analyzer (VNA), by comparison with finite elements simulations of the measurement set-up, using the commercially available software, HFSS. The expected frequency variation is calculated with HFSS and is based on extrapolated complex permittivities, using one relaxation Debye model from permittivity measurements obtained using the Agilent probe.

    Results

    Millimeter wave reflection measurements were performed using the probe in the frequency range of 95-105GHz with three phantoms materials and air. Intermediate measurement results are in good agreement with HFSS simulations, based on the extrapolated complex permittivity. The resonance frequency lowers, from the idle situation when it is probing air, respectively by 0.7, 1.2 and 4.26GHz when a phantom material of 50%, 75% and 95% water content is measured.

    Discussion

    The results of the measurements in our laboratory set-up with three different phantoms indicate that the probe may be able to discriminate between normal and pathological skin tissue, improving the spatial resolution in histology and on skin measurements, due to the highly reduced area of probing.

    Conclusion

    The probe has the potential to discriminate between normal and pathological skin tissue. Further, improved information, compared to the optical histological inspection can be obtained, i.e. the complex permittivity characterization is obtained with a high resolution, due to the highly reduced measurement area of the probe tip.

  • 30.
    Duehrkop, Claudia
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology.
    Leneweit, Gero
    Heyder, Christoph
    Fromell, Karin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology.
    Edwards, Katarina
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Analytical Chemistry.
    Ekdahl, Kristina N
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology.
    Nilsson, Bo
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology.
    Development and characterization of an innovtive heparin coating to stabilize and protect liposomes against adverse immune reactions2016In: Colloids and Surfaces B: Biointerfaces, ISSN 0927-7765, E-ISSN 1873-4367, Vol. 141, p. 576-583Article in journal (Refereed)
    Abstract [en]

    Liposomes have been recognized as excellent drug delivery systems, but when they come in direct contact with different blood components they may trigger an immediate activation of the innate immune system. The aim of the present study was to produce long-circulating, blood-compatible liposomes by developing a construct of liposomes covered by a novel unique heparin complex (CHC; 70 heparin molecules per complex) to avoid recognition by the innate immune system. Unilamellar, cationic liposomes were produced by hand extrusion through a 100-nm polycarbonate membrane. Coating of liposomes with the macromolecular CHC was accomplished by electrostatic interactions. Dynamic light scattering as well as QCM-D measurements were used to verify the electrostatic deposition of the negatively charged CHC to cationic liposomes. The CHC-coated liposomes did not aggregate when in contact with lepirudin anti coagulated plasma. Unlike previous attempts to coat liposomes with heparin, this technique produced freely moveable heparin strands sticking out from the liposome surface, which exposed AT binding sites reflecting the anticoagulant potentials of the liposomes. In experiments using lepirudin-anticoagulated plasma, CHC-coated liposomes, in contrast to non-coated control liposomes, did not activate the complement system, as evidenced by low C3a and sC5b-9 generation and reduced leakage from the liposomes. In conclusion, we show that liposomes can be successfully coated with the biopolymer CHC, resulting in biocompatible and stable liposomes that have significant application potential.

  • 31.
    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.

    The full text will be freely available from 2018-12-22 13:18
  • 32.
    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)
  • 33. Edin, Elle
    et al.
    Simpson, Fiona
    Ruel, Marc
    Hilborn, Jöns
    Griffith, May
    Conductive PEDOT based coatings on microfibrous scaffolds: a nerve guide component2018Manuscript (preprint) (Other (popular science, discussion, etc.))
  • 34. Ekstrand-Hammarstrom, Barbro
    et al.
    Hong, Jaan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology.
    Davoodpour, Padideh
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology.
    Sandholm, Kerstin
    Ekdahl, Kristina N.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology.
    Bucht, Anders
    Nilsson, Bo
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology.
    TiO2 nanoparticles tested in a novel screening whole human blood model of toxicity trigger adverse activation of the kallikrein system at low concentrations2015In: Biomaterials, ISSN 0142-9612, E-ISSN 1878-5905, Vol. 51, p. 58-68Article in journal (Refereed)
    Abstract [en]

    There is a compelling need to understand and assess the toxicity of industrially produced nanoparticles (NPs). In order to appreciate the long-term effects of NPs, sensitive human-based screening tests that comprehensively map the NP properties are needed to detect possible toxic mechanisms. Animal models can only be used in a limited number of test applications and are subject to ethical concerns, and the interpretation of experiments in animals is also distorted by the species differences. Here, we present a novel easy-to-perform highly sensitive whole-blood model using fresh non-anticoagulated human blood, which most justly reflects complex biological cross talks in a human system. As a demonstrator of the tests versatility, we evaluated the toxicity of TiO2 NPs that are widely used in various applications and otherwise considered to have relatively low toxic properties. We show that TiO2 NPs at very low concentrations (50 ng/mL) induce strong activation of the contact system, which in this model elicits thromboinflammation. These data are in line with the finding of components of the contact system in the protein corona of the TiO2 NPs after exposure to blood. The contact system activation may lead to both thrombotic reactions and generation of bradykinin, thereby representing fuel for chronic inflammation in vivo and potentially long-term risk of autoimmunity, arteriosclerosis and cancer. These results support the notion that this novel whole-blood model represents an important contribution to testing of NP toxicity.

  • 35.
    Elgali, Ibrahim
    et al.
    University of Gothenburg.
    Cardemil, Carina
    University of Gothenburg.
    Xia, Wei
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    Omar, Omar
    University of Gothenburg.
    Thomsen, Peter
    Gothenburg University.
    Biological Effects of Strontium-Doped Calcium Phosphate and Hydroxyapatite Granules during Bone Healing in Normal and Ovariectomised Rats2013Conference paper (Refereed)
  • 36. Elgali, Ibrahim
    et al.
    Igawa, Kazuyo
    Palmquist, Anders
    Lenneras, Maria
    Xia, Wei
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    Choi, Sungjin
    Chung, Ung-Il
    Omar, Omar
    Thomsen, Peter
    Molecular and structural patterns of bone regeneration in surgically created defects containing bone substitutes2014In: Biomaterials, ISSN 0142-9612, E-ISSN 1878-5905, Vol. 35, no 10, p. 3229-3242Article in journal (Refereed)
    Abstract [en]

    Several biomaterials have been introduced for bone augmentation. However, information is lacking about the mechanisms of bone regeneration and/or integration of these materials in the recipient bone. This study aimed to determine the molecular and structural events in bone defects after augmentation with synthetic tetrapod-shaped calcium phosphate (Tetrabone; TetraB) compared with natural deproteinized bovine bone (DBB). Defects were created in the epiphyses of rat femurs and filled with TetraB or DBB or left empty (Sham). After 3, 6, 14 and 28 d, samples were harvested for histology, histomorphometry, ultrastructure and gene expression analyses. At 3 d, higher expressions of bone formation (ALP and DC) and remodeling (CatK) genes were detected in TetraB compared with DBB and Sham. Downregulation of bone remodeling genes (TRAP and CatK) was detected in DBB as compared to Sham after 14 d. Histomorphometry at 6 and 14 d demonstrated greater bone contact with the granules in TetraB. At 28 d, a larger bone area per defect was found in TetraB. The present experiments show that a synthetic substitute, consisting of alpha-tricalcium and octacalcium phosphates, induces early osteogenic and osteoclastic activities and promotes bone formation in trabecular bone defects.

  • 37.
    Elgali, Ibrahim
    et al.
    BIOMATCELL VINN Excellence Ctr Biomat & Cell Ther, Gothenburg, Sweden.;Univ Gothenburg, Dept Biomat, Inst Clin Sci, Sahlgrenska Acad, SE-40530 Gothenburg, Sweden..
    Turri, Alberto
    BIOMATCELL VINN Excellence Ctr Biomat & Cell Ther, Gothenburg, Sweden.;Univ Gothenburg, Dept Biomat, Inst Clin Sci, Sahlgrenska Acad, SE-40530 Gothenburg, Sweden.;Publ Dent Hlth Care, Inst Odontol, Branemark Clin, Gothenburg, Sweden..
    Xia, Wei
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    Norlindh, Birgitta
    BIOMATCELL VINN Excellence Ctr Biomat & Cell Ther, Gothenburg, Sweden.;Univ Gothenburg, Dept Biomat, Inst Clin Sci, Sahlgrenska Acad, SE-40530 Gothenburg, Sweden..
    Johansson, Anna
    BIOMATCELL VINN Excellence Ctr Biomat & Cell Ther, Gothenburg, Sweden.;Univ Gothenburg, Dept Biomat, Inst Clin Sci, Sahlgrenska Acad, SE-40530 Gothenburg, Sweden..
    Dahlin, Christer
    BIOMATCELL VINN Excellence Ctr Biomat & Cell Ther, Gothenburg, Sweden.;Univ Gothenburg, Dept Biomat, Inst Clin Sci, Sahlgrenska Acad, SE-40530 Gothenburg, Sweden.;NU Hosp Org, Dept Oral Maxillofacial Surg & Res & Dev, Trollhattan, Sweden..
    Thomsen, Peter
    BIOMATCELL VINN Excellence Ctr Biomat & Cell Ther, Gothenburg, Sweden.;Univ Gothenburg, Dept Biomat, Inst Clin Sci, Sahlgrenska Acad, SE-40530 Gothenburg, Sweden..
    Omar, Omar
    BIOMATCELL VINN Excellence Ctr Biomat & Cell Ther, Gothenburg, Sweden.;Univ Gothenburg, Dept Biomat, Inst Clin Sci, Sahlgrenska Acad, SE-40530 Gothenburg, Sweden..
    Guided bone regeneration using resorbable membrane and different bone substitutes: Early histological and molecular events2016In: Acta Biomaterialia, ISSN 1742-7061, E-ISSN 1878-7568, Vol. 29, p. 409-423Article in journal (Refereed)
    Abstract [en]

    Bone insufficiency remains a major challenge for bone-anchored implants. The combination of guided bone regeneration (GBR) and bone augmentation is an established procedure to restore the bone. However, a proper understanding of the interactions between the bone substitute and GBR membrane materials and the bone-healing environment is lacking. This study aimed to investigate the early events of bone healing and the cellular activities in response to a combination of GBR membrane and different calcium phosphate (CaP) materials. Defects were created in the trabecular region of rat femurs, and filled with deproteinized bovine bone (DBB), hydroxyapatite (HA) or strontium-doped HA (SrHA) or left empty (sham). All the defects were covered with an extracellular matrix membrane. Defects were harvested after 12 h, 3 d and 6 d for histology/histomorphometry, immunohistochemistry and gene expression analyses. Histology revealed new bone, at 6 d, in all the defects. Larger amount of bone was observed in the SrHA-filled defect. This was in parallel with the reduced expression of osteoclastic genes (CR and CatK) and the osteoblast-osteoclast coupling gene (RANKL) in the SrHA defects. Immunohistochemistry indicated fewer osteoclasts in the SrHA defects. The observations of CD68 and periostin-expressing cells in the membrane per se indicated that the membrane may contribute to the healing process in the defect. It is concluded that the bone-promoting effects of Sr in vivo are mediated by a reduction in catabolic and osteoblast-osteoclast coupling processes. The combination of a bioactive membrane and CaP bone substitute material doped with Sr may produce early synergistic effects during GBR. Statement of significance The study provides novel molecular, cellular and structural evidence on the promotion of early bone regeneration in response to synthetic strontium-containing hydroxyapatite (SrHA) substitute, in combination with a resorbable, guided bone regeneration (GBR) membrane. The prevailing view, based mainly upon in vitro data, is that the beneficial effects of Sr are exerted by the stimulation of bone-forming cells (osteoblasts) and the inhibition of bone-resorbing cells (osteoclasts). In contrast, the present study demonstrates that the local effect of Sr in vivo is predominantly via the inhibition of osteoclast number and activity and the reduction of osteoblast-osteoclast coupling. This experimental data will form the basis for clinical studies, using this material as an interesting bone substitute for guided bone regeneration.

  • 38. Engberg, Anna E.
    et al.
    Nilsson, Per H.
    Huang, Shan
    Fromell, Karin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology.
    Hamad, Osama A.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology.
    Mollnes, Tom Eirik
    Rosengren-Holmberg, Jenny P.
    Sandholm, Kerstin
    Teramura, Yuji
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology.
    Nicholls, Ian A.
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC.
    Nilsson, Bo
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology.
    Ekdahl, Kristina N.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology.
    Prediction of inflammatory responses induced by biomaterials in contact with human blood using protein fingerprint from plasma2015In: Biomaterials, ISSN 0142-9612, E-ISSN 1878-5905, Vol. 36, p. 55-65Article in journal (Refereed)
    Abstract [en]

    Inappropriate complement activation is often responsible for incompatibility reactions that occur when biomaterials are used. Complement activation is therefore a criterion included in legislation regarding biomaterials testing. However, no consensus is yet available regarding appropriate complement-activation-related test parameters. We examined protein adsorption in plasma and complement activation/cytokine release in whole blood incubated with well-characterized polymers. Strong correlations were found between the ratio of C4 to its inhibitor C4BP and generation of 10 (mainly pro-inflammatory) cytokines, including IL-17, IFN-gamma, and IL-6. The levels of complement activation products correlated weakly (C3a) or not at all (C5a, sC5b-9), confirming their poor predictive values. We have demonstrated a direct correlation between downstream biological effects and the proteins initially adhering to an artificial surface after contact with blood. Consequently, we propose the C4/C4BP ratio as a robust, predictor of biocompatibility with superior specificity and sensitivity over the current gold standard.

  • 39.
    Engstrand, 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.
    The effect of composition on mechanical properties of brushite cements2014In: Journal of The Mechanical Behavior of Biomedical Materials, ISSN 1751-6161, E-ISSN 1878-0180, Vol. 29, p. 81-90Article in journal (Refereed)
    Abstract [en]

    Due to a fast setting reaction, good biological properties, and easily available starting materials, there has been extensive research within the field of brushite cements as bone replacing material. However, the fast setting of brushite cement gives them intrinsically low mechanical properties due to the poor crystal compaction during setting. To improve this, many additives such as citric acid, pyrophosphates, and glycolic acid have been added to the cement paste to retard the crystal growth. Furthermore, the incorporation of a filler material could improve the mechanical properties when used in the correct amounts. In this study, the effect of the addition of the two retardants, disodium dihydrogen pyrophosphate and citric acid, together with the addition of β-TCP filler particles, on the mechanical properties of a brushite cement was investigated. The results showed that the addition of low amounts of a filler (up to 10%) can have large effects on the mechanical properties. Furthermore, the addition of citric acid to the liquid phase makes it possible to use lower liquid-to-powder ratios (L/P), which strongly affects the strength of the cements. The maximal compressive strength (41.8 MPa) was found for a composition with a molar ratio of 45:55 between monocalcium phosphate monohydrate and beta-tricalcium phosphate, an L/P of 0.25 ml/g and a citric acid concentration of 0.5 M in the liquid phase.

  • 40.
    Engstrand, Johanna
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    Unosson, Erik
    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.
    A dental cement capable of calcium phosphate formation on its surface during water storage2011Conference paper (Refereed)
  • 41.
    Engstrand, Johanna
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    Åberg, Jonas
    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.
    Influence of water content on hardening and handling of a premixed calcium phosphate cement2013In: Materials science & engineering. C, biomimetic materials, sensors and systems, ISSN 0928-4931, E-ISSN 1873-0191, Vol. 33, no 1, p. 527-531Article in journal (Refereed)
    Abstract [en]

    Handling of calcium phosphate cements is difficult, where problems often arise during mixing, transferring tosyringes, and subsequent injection. Via the use of premixed cements the risk of handling complications is reduced. However, for premixed cements to work in a clinical situation the setting time needs to be improved. The objective of this study is to investigate the influence of the addition of water on the properties of premixed cement. Monetite-forming premixed cements with small amounts of added water (less than 6.8 wt.%) were prepared and the influence on injectability, working time, setting time and mechanical strength was evaluated. The results showed that the addition of small amounts of water had significant influence on the properties of the premixed cement. With the addition of just 1.7 wt.% water, the force needed to extrude the cement from a syringe was reduced from 107 (±15)N to 39 (±9)N, the compression strength was almost doubled, and the setting time decreased from 29 (±4)min to 19 (±2)min, while the working time remained 5 to 6 h. This study demonstrates the importance of controlling the water content in premixed cement pastes and how water can be used to improve the properties of premixed cements.

  • 42.
    Gallinetti, Sara
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences. Universitat Politècnica de Cataluny; Barcelona Research Center in Multiscale Science and Engineering, UPC, Barcelona, Spain .
    Mestres, Gemma
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Microsystems Technology.
    Canal, Cristina
    Universitat Politècnica de Catalunya; Barcelona Research Center in Multiscale Science and Engineering.
    Persson, Cecilia
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    Ginebra, Maria-Pau
    Universitat Politècnica de Catalunya; Barcelona Research Center in Multiscale Science and Engineering.
    A novel strategy to enhance interfacial adhesion in fiber-reinforced calcium phosphate cement2017In: Journal of The Mechanical Behavior of Biomedical Materials, ISSN 1751-6161, E-ISSN 1878-0180, Vol. 75, p. 495-503Article in journal (Refereed)
    Abstract [en]

    Calcium phosphate cements (CPCs) are extensively used as synthetic bone grafts, but their poor toughness limits their use to non-load-bearing applications. Reinforcement through introduction of fibers and yarns has been evaluated in various studies but always resulted in a decrease in elastic modulus or bending strength when compared to the CPC matrix. The aim of the present work was to improve the interfacial adhesion between fibers and matrix to obtain tougher biocompatible fiber-reinforced calcium phosphate cements (FRCPCs). This was done by adding a polymer solution to the matrix, with chemical affinity to the reinforcing chitosan fibers, namely trimethyl chitosan (TMC). The improved wettability and chemical affinity of the chitosan fibers with the TMC in the liquid phase led to an enhancement of the interfacial adhesion. This resulted in an increase of the work of fracture (several hundred-fold increase), while the elastic modulus and bending strength were maintained similar to the materials without additives. Additionally the TMC-modified CPCs showed suitable biocompatibility with an osteoblastic cell line.

    The full text will be freely available from 2019-08-16 16:31
  • 43.
    Gou, Zhongru
    et al.
    Zhejiang University.
    Ballo, Ahmed
    Gothenburg University.
    Xia, Wei
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    Biomimetic preparation and biomineralization of bioceramics2012In: Advanced bioactive inorganic materials for bone regeneration and drug delivery, CRC Press and Taylor & Francis , 2012Chapter in book (Refereed)
  • 44.
    Grandfield, Kathryn
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    Pujari, Shiuli
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    Ott, Marjam
    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.
    Effect of Calcium and Strontium on Mesoporous Titania Coatings for Implant Applications2013In: Journal of Biomaterials and Nanobiotechnology, ISSN 2158-7027, E-ISSN 2158-7043, Vol. 4, no 2, p. 107-113Article in journal (Refereed)
    Abstract [en]

    ncreasing interest in the role of ions such as calcium and strontium in bone formation has called for the investigation of multifunctional ion-doped implant coatings. Mesoporous titania coatings incorporating calcium or strontium enabled a unique pore morphology and potential for drug delivery. Coatings were produced on titanium by an evaporation induced self-assembly method with the addition of calcium or strontium to the sol causing a shift in morphology from a hexagonally-packed to a worm-like porous network. Pore sizes ranged from 3.8 - 5 nm and coatings exhibited high surface areas between 181 - 215.5 m2/g, as measured by N2adsorption-desorption. Coatings were loaded with 1 mg/ml Cephalothin, and showed sustained release of the antibiotic over one week in vitro. Cell studies confirmed that the ion addition had no toxic effect on human-like osteoblastic SaOS-2 cells. The results of this study suggest the potential for mesoporous coatings with calcium or strontium incorporation for direct bone-interfacing and combined drug delivery implant applications.

  • 45.
    Grandfield, Kathryn
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    Pujari, Shiuli
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    Ott, Marjam
    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.
    Mesoporous titania implant coatings with and without calcium and strontium ion incorporation2012Conference paper (Refereed)
  • 46.
    Hoess, Andreas
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    Ferraz, Natalia
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Nanotechnology and Functional Materials.
    Thormann, Annika
    Fraunhofer Institute for Mechanics of Materials IWMH, Halle, Germany.
    Heilmann, Andreas
    Fraunhofer Institute for Mechanics of Materials IWMH, Halle, Germany.
    Shen, Jinhui
    Department of Bioengineering, The University of Texas at Arlington, Texas, USA.
    Tang, Liping
    Department of Bioengineering, The University of Texas at Arlington, Texas, USA.
    Karlsson Ott, Marjam
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    In Vivo Acute Inflammatory Response to Nanoporous Alumina2011In: 24th European Conference on Biomaterials, Dublin, September 04-08, 2011., 2011Conference paper (Refereed)
  • 47.
    Hoess, Andreas
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    López, Alejandro
    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.
    Persson, Cecilia
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    Effects of a natural oil on the mechanical properties and cytotoxicity of PMMA bone cement2011In: Annual Meeting of the Scandinavian Society for Biomaterials, 2011, Vol. 21, no S1, p. 23-Conference paper (Refereed)
  • 48.
    Holub, Ondrej
    et al.
    University of Leeds.
    López, Alejandro
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    Borse, Vishal
    University of Leeds.
    Engqvist, Håkan
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    Kapur, Nik
    University of Leeds.
    Hall, Richard M.
    University of Leeds.
    Persson, Cecilia
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    Biomechanics of low-modulus and standard acrylic bone cements in simulated vertebroplasty: A human ex vivo study2015In: Journal of Biomechanics, ISSN 0021-9290, E-ISSN 1873-2380, Vol. 48, no 12, p. 3258-3266Article in journal (Refereed)
    Abstract [en]

    The high stiffness of bone cements used in vertebroplasty has been hypothesised to contribute to the propensity of adjacent vertebral fractures after treatment. Therefore, new low-modulus cements have been developed; however, there are currently no studies assessing the biomechanical aspects of vertebroplasty with these cements in an ex vivo non-prophylactic model. In this study, we induced wedge fractures through eccentric uniaxial compression to single whole-vertebrae, before and after augmentation with either standard or low-modulus cement. Compressive strength and stiffness of individual vertebrae were measured, on 19 samples from metastatic spines and 20 samples from elderly, osteopenic spines. While both cement types increased the strength of both the metastatic (+34% and +63% for standard and low-modulus cement, respectively) and the elderly vertebrae (+303% and +113%, respectively), none of them restored the initial stiffness of metastatic specimens (−51% and −46%, respectively). Furthermore, low-modulus cement gave a lower total stiffness (−13%) of elderly specimens whereas standard cement increased it above initial levels (+17%). Results show that vertebroplasty with low-modulus cement could provide restoration of the initial stiffness while increasing the strength of fractured elderly vertebrae and hence represent a treatment modality which is closer to pre-augmented behaviour. Also, this study indicates that stiffness-modified cement needs to be optimised for patient/pathology specific treatment.

    The full text will be freely available from 2019-07-16 00:00
  • 49.
    Hong, Jaan
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology.
    Kurt, Seta
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Clinical Immunology.
    Thor, Andreas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Oral and Maxillofacial Surgery.
    A Hydrophilic Dental Implant Surface Exhibit Thrombogenic Properties In Vitro2013In: Clinical Implant Dentistry and Related Research, ISSN 1523-0899, E-ISSN 1708-8208, Vol. 15, no 1, p. 105-112Article in journal (Refereed)
    Abstract [en]

    Background:

    Surface modifications of dental implants have gained attention during several years and the thrombotic response from blood components with these materials has become more important during recent years.

    Purpose:

    The aims of this study were to evaluate the thrombogenic response of whole blood, in contact with clinically used dental surfaces, Sandblasted Large grit Acid etched titanium (SLA) and Sandblasted Large grit Acid etched, and chemically modified titanium with hydrophilic properties (SLActive).

    Methods:

    An in vitro slide chamber model, furnished with heparin, was used in which whole blood came in contact with slides of the test surfaces. After incubation (60-minute rotation at 22 rpm in a 37°C water bath), blood was mixed with ethylenediaminetetraacetic acid (EDTA) or citrate, further centrifuged at +4°C. Finally, plasma was collected pending analysis.

    Results:

    Whole blood in contact with surfaces resulted in significantly higher binding of platelets to the hydrophilic surface, accompanied by a significant increase of contact activation of the coagulation cascade. In addition, the platelet activation showed a similar pattern with a significant elevated release of β-TG from platelet granule.

    Conclusions:

    The conclusion that can be drawn from the results in our study is that the hydrophilic modification seems to augment the thrombogenic properties of titanium with implications for healing into bone of, that is titanium dental implants.

  • 50.
    Hong, Jaan
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Clinical Immunology and Transfusion Medicine. Klinisk immunologi.
    Nilsson Ekdahl, Kristina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Clinical Immunology and Transfusion Medicine.
    Reynolds, Helena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Clinical Immunology and Transfusion Medicine.
    Larsson, Rolf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Clinical Immunology and Transfusion Medicine.
    Nilsson, Bo
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Clinical Immunology and Transfusion Medicine.
    A new in vitro model to study interaction between whole blood and biomaterials. Studies of platelet and coagulation activation and the effect of aspirin1999In: Biomaterials, ISSN 0142-9612, E-ISSN 1878-5905, Vol. 20, no 7, p. 603-611Article in journal (Refereed)
    Abstract [en]

    We have developed a versatile in vitro chamber model with a double purpose: first, to be able to study mechanisms of bio- incompatibility, and, second, to test biomaterials at all levels of interactions, in whole blood. The use of biomaterials in the form of microscope slides as walls in the chamber makes it possible to analyse both the biomaterial surface with regard to protein and cell binding, as well as the molecular events taking place in the fluid. Incubation of blood in the chamber, for 60 min at 37°C resulted in the rapid binding of complement and coagulation proteins and of leukocytes and platelets to polyvinylchloride (PVC) slides. The cells formed a layer which more or less covered the underlying surface. Unlike complement activation, as reflected by soluble C3a and C5b-9, the thrombin—antithrombin formation was completely nullified in cell-depleted plasma. Despite the fact that throm- bin—antithrombin generation was also negligible in platelet-rich plasma, inhibition of platelet aggregation on the material surface with aspirin resulted in suppressed generation of thrombin—antithrombin complexes. Taken together, the coagulation activation in the chamber was dependent on the presence of blood cells which suggests that bound/aggregated platelets initiate a sequence of events involving leukocytes that results in coagulation activation. 

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