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  • 1.
    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.

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  • 2.
    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)
  • 3.
    Ajaxon, Ingrid
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    Holmberg, Anders
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    Öhman, Caroline
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    Persson, Cecilia
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    Fatigue performance of a high-strength, degradable calcium phosphate bone cement2018In: Journal of The Mechanical Behavior of Biomedical Materials, ISSN 1751-6161, E-ISSN 1878-0180, Vol. 79, p. 46-52Article in journal (Refereed)
    Abstract [en]

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

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  • 4.
    Ajaxon, Ingrid
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    Holmberg, Anders
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    Öhman Mägi, Caroline
    Persson, Cecilia
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    Fatigue life of a brushite cement under cyclic compressive loading2017Conference paper (Refereed)
  • 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
    Biomaterials, Biomechanics and Tissue Engineering Group, Dept. of Materials Science and Metallurgy, Technical University of Catalonia .
    Ginebra, Maria-Pau
    Biomaterials, Biomechanics and Tissue Engineering Group, Dept. of Materials Science and Metallurgy, Technical University of Catalonia .
    Öhman, Caroline
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    Persson, Cecilia
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    A non-drying porosity evaluation method for calcium phosphate cements2014In: 26th Symposium and Annual Meeting of the International Society for Ceramics in Medicine, 2014, p. 68-68Conference paper (Refereed)
  • 8.
    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. 

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  • 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.
    Compressive Fatigue Properties of Acidic Calcium Phosphate Cement2014In: Proceedings of 7th World Congress of Biomechanics, 2014Conference paper (Refereed)
  • 10.
    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. 

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    Long-term in vitro degradation of a high-strength brushite cement in water, PBS, and serum solution
  • 11.
    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. 

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  • 12.
    Altundal, Sahin
    et al.
    nstitute of Biomaterials and Biomechanics, Riga Technical University, Latvia.
    Gross, Karlis Agris
    nstitute of Biomaterials and Biomechanics, Riga Technical University, Latvia.
    Öhman Mägi, Caroline
    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.
    Improving the Flexural Strength Test of Brushite Cement2015In: Key Engineering Materials, ISSN 1013-9826, E-ISSN 1662-9795, Vol. 631, p. 67-72Article in journal (Refereed)
  • 13.
    Baleani, Massimiliano
    et al.
    Laboratorio di Tecnologia Medica, Istituto Ortopedico Rizzoli, Bologna, Italy.
    Fognani, Roberta
    Laboratorio di Tecnologia Medica, Istituto Ortopedico Rizzoli, Bologna, Italy.
    Feresini, Chiara
    Centro Ceramico Bologna, Bologna, Italy.
    Öhman, Caroline
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    Spagnolo, Claudia
    Laboratorio di Tecnologia Medica, Istituto Ortopedico Rizzoli, Bologna, Italy.
    Baruffaldi, Fabio
    Laboratorio di Tecnologia Medica, Istituto Ortopedico Rizzoli, Bologna, Italy.
    Real wet density of bone tissue: Does it depend on tissue type and subject?2014In: Proceedings of 7th World Congress of Biomechanics, 2014, 2014Conference paper (Refereed)
  • 14.
    Barba, Albert
    et al.
    Univ Politecn Cataluna, Dept Mat Sci & Met Engn, Biomat Biomech & Tissue Engn Grp, Ave Eduard Maristany 10-14, Barcelona 08019, Spain;Univ Politecn Cataluna, Barcelona Res Ctr Multiscale Sci & Engn, Ave Eduard Maristany 10-14, Barcelona 08019, Spain.
    Diez-Escudero, Anna
    Univ Politecn Cataluna, Dept Mat Sci & Met Engn, Biomat Biomech & Tissue Engn Grp, Ave Eduard Maristany 10-14, Barcelona 08019, Spain;Univ Politecn Cataluna, Barcelona Res Ctr Multiscale Sci & Engn, Ave Eduard Maristany 10-14, Barcelona 08019, Spain.
    Espanol, Montserrat
    Univ Politecn Cataluna, Dept Mat Sci & Met Engn, Biomat Biomech & Tissue Engn Grp, Ave Eduard Maristany 10-14, Barcelona 08019, Spain;Univ Politecn Cataluna, Barcelona Res Ctr Multiscale Sci & Engn, Ave Eduard Maristany 10-14, Barcelona 08019, Spain.
    Bonany, Mar
    Univ Politecn Cataluna, Dept Mat Sci & Met Engn, Biomat Biomech & Tissue Engn Grp, Ave Eduard Maristany 10-14, Barcelona 08019, Spain;Univ Politecn Cataluna, Barcelona Res Ctr Multiscale Sci & Engn, Ave Eduard Maristany 10-14, Barcelona 08019, Spain.
    Maria Sadowska, Joanna
    Univ Politecn Cataluna, Dept Mat Sci & Met Engn, Biomat Biomech & Tissue Engn Grp, Ave Eduard Maristany 10-14, Barcelona 08019, Spain;Univ Politecn Cataluna, Barcelona Res Ctr Multiscale Sci & Engn, Ave Eduard Maristany 10-14, Barcelona 08019, Spain.
    Guillem-Marti, Jordi
    Univ Politecn Cataluna, Dept Mat Sci & Met Engn, Biomat Biomech & Tissue Engn Grp, Ave Eduard Maristany 10-14, Barcelona 08019, Spain;Univ Politecn Cataluna, Barcelona Res Ctr Multiscale Sci & Engn, Ave Eduard Maristany 10-14, Barcelona 08019, Spain.
    Öhman-Mägi, Caroline
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    Persson, Cecilia
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    Manzanares, Maria-Cristina
    Univ Barcelona, Dept Pathol & Expt Therapeut, Human Anat & Embryol Unit, Barcelona 08907, Spain.
    Franch, Jordi
    Univ Autonoma Barcelona, Sch Vet, Small Anim Surg Dept, Bone Healing Grp, E-08193 Barcelona, Spain.
    Ginebra, Maria-Pau
    Univ Politecn Cataluna, Dept Mat Sci & Met Engn, Biomat Biomech & Tissue Engn Grp, Ave Eduard Maristany 10-14, Barcelona 08019, Spain;Univ Politecn Cataluna, Barcelona Res Ctr Multiscale Sci & Engn, Ave Eduard Maristany 10-14, Barcelona 08019, Spain;Barcelona Inst Technol BIST, Inst Bioengn Catalonia IBEC, Barcelona 08028, Spain.
    Impact of Biomimicry in the Design of Osteoinductive Bone Substitutes: Nanoscale Matters2019In: ACS Applied Materials and Interfaces, ISSN 1944-8244, E-ISSN 1944-8252, Vol. 11, no 9, p. 8818-8830Article in journal (Refereed)
    Abstract [en]

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

  • 15.
    Barba, Albert
    et al.
    Biomaterials, Biomechanics and Tissue Engineering Group, Department of Materials Science and Metallurgical Engineering, Universitat Politecnica de Catalunya.
    Diez-Escudero, Anna
    Biomaterials, Biomechanics and Tissue Engineering Group, Department of Materials Science and Metallurgical Engineering, Universitat Politecnica de Catalunya.
    Maazouz, Yassine
    Biomaterials, Biomechanics and Tissue Engineering Group, Department of Materials Science and Metallurgical Engineering, Universitat Politecnica de Catalunya.
    Rappe, Katrin
    Bone Healing Group, Small Animal Surgery Department, Veterinary School, Universitat Autonoma de Barcelona.
    Espanol, Montserrat
    Barcelona Research Center in Multiscale Science and Engineering, Universitat Politecnica de Catalunya.
    Montufar, Edgar B
    Barcelona Research Center in Multiscale Science and Engineering, Universitat Politecnica de Catalunya.
    Bonany, Mar
    Barcelona Research Center in Multiscale Science and Engineering, Universitat Politecnica de Catalunya.
    Sadowska, Joanna M
    Barcelona Research Center in Multiscale Science and Engineering, Universitat Politecnica de Catalunya.
    Guillem-Marti, Jordi
    Barcelona Research Center in Multiscale Science and Engineering, Universitat Politecnica de Catalunya.
    Öhman, Caroline
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    Persson, Cecilia
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    Manzanares, Maria-Cristina
    Human Anatomy and Embryology Unit, Department of Pathology and Experimental Therapeutics, Universitat de Barcelona.
    Franch, Jordi
    Bone Healing Group, Small Animal Surgery Department, Veterinary School, Universitat Autonoma de Barcelona.
    Ginebra, Maria-Pau
    Biomaterials, Biomechanics and Tissue Engineering Group, Department of Materials Science and Metallurgical Engineering, Universitat Politecnica de Catalunya.
    Osteoinduction by Foamed and 3D-Printed Calcium Phosphate Scaffolds: Effect of Nanostructure and Pore Architecture2017In: ACS Applied Materials and Interfaces, ISSN 1944-8244, E-ISSN 1944-8252, Vol. 9, no 48, p. 41722-41736Article in journal (Refereed)
    Abstract [en]

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

  • 16.
    Barba, Albert
    et al.
    Biomaterials, Biomechanics and Tissue Engineering Group, Department of Materials Science and Metallurgical Engineering, Universitat Politècnica de Catalunya.
    Maazouz, Yassine
    Biomaterials, Biomechanics and Tissue Engineering Group, Department of Materials Science and Metallurgical Engineering, Universitat Politècnica de Catalunya.
    Diez-Escudero, Anna
    Biomaterials, Biomechanics and Tissue Engineering Group, Department of Materials Science and Metallurgical Engineering, Universitat Politècnica de Catalunya.
    Rappe, Katrin
    Bone Healing Group, Small Animal Surgery Department, Veterinary School, Universitat Autònoma de Barcelona.
    Espanol, Montserrat
    Biomaterials, Biomechanics and Tissue Engineering Group, Department of Materials Science and Metallurgical Engineering, Universitat Politècnica de Catalunya.
    Montufar, Edgar
    Biomaterials, Biomechanics and Tissue Engineering Group, Department of Materials Science and Metallurgical Engineering, Universitat Politècnica de Catalunya.
    Öhman, Caroline
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    Persson, Cecilia
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    Fontecha, Pedro
    Bone Healing Group, Small Animal Surgery Department, Veterinary School, Universitat Autònoma de Barcelona.
    Manzanares, Maria-Cristina
    Human Anatomy and Embryology Unit, Department of Pathology and Experimental Therapeutics, Universitat de Barcelona.
    Franch, Jordi
    Bone Healing Group, Small Animal Surgery Department, Veterinary School, Universitat Autònoma de Barcelona.
    Ginebra, Maria-Pau
    Biomaterials, Biomechanics and Tissue Engineering Group, Department of Materials Science and Metallurgical Engineering, Universitat Politècnica de Catalunya.
    Osteogenesis by foamed and 3D-printed nanostructured calcium phosphate scaffolds: Effect of pore architecture2018In: Acta Biomaterialia, ISSN 1742-7061, E-ISSN 1878-7568, Vol. 79, p. 135-147Article in journal (Refereed)
    Abstract [en]

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

  • 17.
    Chen, Song
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    Öhman, Caroline
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    Jefferies, Steven R.
    Temple Univ, Dept Restorat Dent, Kornberg Sch Dent, Philadelphia, PA 19122 USA.
    Gray, Holly
    Temple Univ, Dept Restorat Dent, Kornberg Sch Dent, Philadelphia, PA 19122 USA.
    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.
    Compressive fatigue limit of four types of dental restorative materials2016In: Journal of The Mechanical Behavior of Biomedical Materials, ISSN 1751-6161, E-ISSN 1878-0180, Vol. 61, p. 283-289Article in journal (Refereed)
    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.

  • 18.
    Chen, Song
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    Öhman, Caroline
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    Jefferies, Steven R.
    Gray, Holly
    Xia, Wei
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    Engqvist, Håkan
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    Quasi-static compressive strength and compressive fatigue limit of dental cements2016Conference paper (Refereed)
  • 19.
    Dyal Ukabhai, K.
    et al.
    Univ Witwatersrand, Sch Chem & Met Engn, Johannesburg, South Africa.;Ctr Excellence Strong Mat, DSI NRF, Johannesburg, South Africa..
    Curle, U. A.
    CSIR, Adv Mat Engn, Mfg Cluster, Pretoria, South Africa..
    Masia, N. D. E.
    Univ Witwatersrand, Sch Chem & Met Engn, Johannesburg, South Africa.;Ctr Excellence Strong Mat, DSI NRF, Johannesburg, South Africa.;MINTEK, Randburg, South Africa..
    Smit, M.
    MINTEK, Randburg, South Africa..
    Mwamba, I. A.
    MINTEK, Randburg, South Africa..
    Norgren, S.
    Lund Univ, Dept Mech Engn Sci, Lund, Sweden..
    Öhman, Caroline
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Materials Science and Engineering, Applied Material Science.
    Hashe, N. G.
    Nelson Mandela Univ NMU, Dept Phys, Gqeberha, South Africa..
    Cornish, L. A.
    Univ Witwatersrand, Sch Chem & Met Engn, Johannesburg, South Africa.;Ctr Excellence Strong Mat, DSI NRF, Johannesburg, South Africa..
    Formation of Ti2Cu in Ti-Cu Alloys2022In: JOURNAL OF PHASE EQUILIBRIA AND DIFFUSION, ISSN 1547-7037, Vol. 43, no 3, p. 332-344Article in journal (Refereed)
    Abstract [en]

    One of the major issues with dental implants is failure due to bacterial infection, and additions of copper are known to improve the antimicrobial properties of Ti alloys. There are inconsistencies in the Ti rich area of the Cu-Ti binary phase diagram, hence the need to find out if Ti2Cu or Ti3Cu is formed, and to identify the type of formation of Ti2Cu. Four alloys: 20, 33, 40 and 50 Cu (mass%) were produced by arc melting and studied using SEM, XRD and DSC. The reactions were derived, and the temperatures of the reactions were determined by DSC. The formation of Ti2Cu is congruent, and no Ti3Cu was found.

  • 20.
    Fowler, Lee
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    Engqvist, Håkan
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    Öhman-Mägi, Caroline
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    Effect of copper ion concentration on bacteria and cells2019In: Materials, ISSN 1996-1944, E-ISSN 1996-1944, Vol. 12, no 22, article id 3798Article in journal (Refereed)
    Abstract [en]

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

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  • 21.
    Fowler, Lee
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    Janson, Oscar
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    Engqvist, Håkan
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    Norgren, Susanne
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    Öhman, Caroline
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    Antibacterial investigation of titanium-copper alloys using luminescent Staphylococcus epidermidis in a direct contact test2019In: Materials science & engineering. C, biomimetic materials, sensors and systems, ISSN 0928-4931, E-ISSN 1873-0191, Vol. 97, p. 707-714Article in journal (Refereed)
    Abstract [en]

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

  • 22.
    Fowler, Lee
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    Masia, Nomsombuluko
    Advanced Materials Division, Mintek, Randburg 2124, South Africa; School of Chemical and Metallurgical Engineering, and DST-NRF Centre of Excellence in Strong Materials, hosted by the University of the Witswatersrand, Johannesburg 2000, South Africa.
    Cornish, Lesley A.
    School of Chemical and Metallurgical Engineering, and DST-NRF Centre of Excellence in Strong Materials, hosted by the University of the Witswatersrand, Johannesburg 2000, South Africa.
    Chown, Lesley H.
    School of Chemical and Metallurgical Engineering, and DST-NRF Centre of Excellence in Strong Materials, hosted by the University of the Witswatersrand, Johannesburg 2000, South Africa.
    Engqvist, Håkan
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    Norgren, Susanne
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    Öhman-Mägi, Caroline
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    Development of Antibacterial Ti-Cu-x Alloys for Dental Applications: Effects of Ageing for Alloys with Up to 10 wt% Cu2019In: Materials, ISSN 1996-1944, E-ISSN 1996-1944, Vol. 12, no 23, article id 4017Article in journal (Refereed)
    Abstract [en]

    Peri-implantitis, a disease caused by bacteria, affects dental implants in patients. It is widely treated with antibiotics, however, with growing antibiotic resistance new strategies are required. Titanium-copper alloys are prospective antibacterial biomaterials, with the potential to be a remedy against peri-implantitis and antibiotic resistance. The aim of this study was to investigate Ti-Cux alloys, exploring how Cu content (up to 10 wt%) and ageing affect the material properties. Electron microscopy, X-ray diffraction, hardness testing, bacteriological culture, and electrochemical testing were employed to characterize the materials. It was found that alloys with above 3 wt% Cu had two phases and ageing increased the volume fraction of Ti2Cu. An un-aged alloy of 5 wt% Cu showed what could be Ti3Cu, in addition to the α-Ti phase. The hardness gradually increased with increased Cu additions, while ageing only affected the alloy with 10 wt% Cu (due to changes in microstructure). Ageing resulted in faster passivation of the alloys. After two hours the aged 10 wt% Cu alloy was the only material with an antibacterial effect, while after six hours, bacteria killing occurred in all alloys with above 5 wt% Cu. In conclusion, it was possible to tune the material and antibacterial properties of Ti-Cux alloys by changing the Cu concentration and ageing, which makes further optimization towards an antibacterial material promising.

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  • 23.
    Fowler, Lee
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    Van Vuuren, Arno Janse
    Centre for High Resolution Transmission Electron Microscopy, Department of Physics, Nelson Mandela University, 6031 Port Elizabeth, South Africa.
    Goosen, William
    Centre for High Resolution Transmission Electron Microscopy, Department of Physics, Nelson Mandela University, 6031 Port Elizabeth, South Africa.
    Engqvist, Håkan
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    Öhman-Mägi, Caroline
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    Norgren, Susanne
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    Investigation of copper alloying in a TNTZ-Cux alloy2019In: Materials, ISSN 1996-1944, E-ISSN 1996-1944, Vol. 12, no 22, article id 3691Article in journal (Refereed)
    Abstract [en]

    Alloying copper into pure titanium has recently allowed the development of antibacterial alloys. The alloying of biocompatible elements (Nb, Ta and Zr) into pure titanium has also achieved higher strengths for a new alloy of Ti-1.6 wt.% Nb-10 wt.% Ta-1.7 wt.% Zr (TNTZ), where strength was closer to Ti-6Al-4V and higher than grade 4 titanium. In the present study, as a first step towards development of a novel antibacterial material with higher strength, the existing TNTZ was alloyed with copper to investigate the resultant microstructural changes and properties. The initial design and modelling of the alloy system was performed using the calculation of phase diagrams (CALPHAD) methods, to predict the phase transformations in the alloy. Following predictions, the alloys were produced using arc melting with appropriate heat treatments. The alloys were characterized using energy dispersive X-ray spectroscopy in scanning transmission electron microscopy (STEM-EDS) with transmission Kikuchi diffraction (TKD). The manufactured alloys had a three-phased crystal structure that was found in the alloys with 3 wt.% Cu and higher, in line with the modelled alloy predictions. The phases included the α-Ti (HCP-Ti) with some Ta present in the crystal, Ti2Cu, and a bright phase with Ti, Cu and Ta in the crystal. The Ti2Cu crystals tended to precipitate in the grain boundaries of the α-Ti phase and bright phase. The hardness of the alloys increased with increased Cu addition, as did the presence of the Ti2Cu phase. Further studies to optimize the alloy could result in a suitable material for dental implants.

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  • 24.
    Franck, Marina Christina Mikaela
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology.
    Weman, Hannah M.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Genomics and Neurobiology.
    Ceder, Mikaela M.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Genomics and Neurobiology.
    Ahemaiti, Aikeremu
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Genomics and Neurobiology.
    Ma, Haisha
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Bengtsson, Erica
    Magnusson, Kajsa A.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Genomics and Neurobiology.
    Koning, Harmen Kornelis
    Öhman, Caroline
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Materials Science and Engineering, Applied Material Science.
    Lagerström, Malin C.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Genomics and Neurobiology.
    Urocortin3-expressing neurons in sensory transmissionManuscript (preprint) (Other academic)
    Abstract [en]

    Urocortin 3 (UCN3) is a neuropeptide involved in mechanosensation and stress regulation, and Ucn3-Cre neurons have been assigned a role in mechanical itch. Here, we show that Ucn3 marks a population of excitatory neurons in the mouse dorsal horn, divided into two non-overlapping subpopulations expressing protein kinase C g or calretinin/calbindin 2. Chemogenetic activation of spinal Ucn3-Cre neurons evoked a targeted biting/licking behavior towards the corresponding dermatome. Genetic deletion of vesicular glutamate transporter 2 (VGLUT2) in Ucn3-Cre neurons removed the phenotype, showing that the biting/licking behavior is VGLUT2-dependent. Conditional deletion of VGLUT2 did not affect acute thermal or mechanical withdrawal responses, nor thermal withdrawal responses after nerve growth factor-induced hypersensitivity or the prurifensive response to 48/80 or von Frey stimuli applied in nape. Instead, we found that a group of spinal Ucn3 neurons were activated in response to artificial scratching or 48/80-induced itch. Electrophysiological experiments showed that spinal Ucn3 neurons received both glycinergic and GABAergic tonic inhibition, and monosynaptic inputs from both Aβ and C fibers, which could be confirmed by rabies tracing. Spinal Ucn3/Ucn3-Cre neurons thus represent a mechanically sensitive population with several roles in the itch-scratch cycle. 

  • 25.
    Gallinetti, Sara
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    Lemoine, Delphine
    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.
    Novel multiphasic calcium phosphate cements with enhanced degradative properties2016Conference paper (Refereed)
  • 26.
    Gallinetti, Sara
    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.
    Long-term degradation of novel multiphasic calcium phosphate cements2017Conference paper (Refereed)
  • 27.
    Gallinetti, Sara.
    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.
    Micro-CT imaging as a tool to study the fracture behaviour of bone cements2015Conference paper (Refereed)
  • 28.
    Gallinetti, Sara
    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.
    Micro-computed tomography: a tool to study the fracture behaviour of calcium phosphate cements2016Conference paper (Refereed)
  • 29.
    Gallinetti, Sara
    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.
    Micro-CT as a tool to study crack initiation and propagation in ceramic bone cements2018Conference paper (Refereed)
  • 30.
    Ghandour, Salim
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Materials Science and Engineering.
    Christie, Iain
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Materials Science and Engineering.
    Öhman, Caroline
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Materials Science and Engineering, Applied Material Science.
    Persson, Cecilia
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Materials Science and Engineering.
    Quasi-static and dynamic mechanical properties of a low-modulus bone cement for spinal applications2023In: Open Research Europe, E-ISSN 2732-5121, Vol. 3, article id 203Article in journal (Refereed)
    Abstract [en]

    Background:

    Polymethylmethacrylate (PMMA) bone cement is extensively used in spinal procedures such as vertebroplasty and kyphoplasty, while its use in percutaneous cement discoplasty (PCD) is not yet widely spread. A main issue for both application sites, vertebra and disc, is the mismatch in stiffness between cement and bone, potentially resulting in adjacent vertebral fractures and adjacent segment disease. Tailoring the cement modulus using additives is hence an interesting strategy. However, there is a lack of data on the tensile and tension-compression fatigue properties of these cements, relevant to the newly researched indication of PCD. 

    Method:

    A commercial PMMA cement (VS) was modified with 12%vol of linoleic acid (VSLA) and tested for quasi-static tensile properties. Additionally, tension-compression fatigue testing with amplitudes ranging from +/-5MPa to +/-7MPa and +/-9MPa was performed, and a Weibull three-parameter curve fit was used to calculate the fatigue parameters. 

    Results:

    Quasi-static testing revealed a significant reduction in VSLA’s Young’s Modulus (E=581.1±126.4MPa) compared to the original cement (E=1478.1±202.9MPa). Similarly, the ultimate tensile stress decreased from 36.6±1.5MPa to 11.6±0.8MPa. Thus, VSLA offers improved compatibility with trabecular bone properties. Fatigue testing of VSLA revealed that as the stress amplitude increased the Weibull mean number decreased from 3591 to 272 and 91 cycles, respectively. In contrast, the base VS cement reached run-out at the highest stress amplitude. However, the lowest stress amplitude used exceeds the pressures recorded in the disc in vivo, and VSLA displayed a similar fatigue life range to that of the annulus fibrosis tissue.

    Conclusions:

    While the relevance of fully reversed tension-compression fatigue testing can be debated for predicting cement performance in certain spinal applications, the results of this study can serve as a benchmark for comparison of low-modulus cements for the spine. Further investigations are necessary to assess the clinical feasibility and effectiveness of these cements.

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  • 31.
    Habicher, Judith
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Organismal Biology, Evolution and Developmental Biology. Department of Cellular, Computational and Integrative Biology (CIBIO), University of Trento, Trento, Italy.
    Varshney, Gaurav K.
    Genes & Human Disease Research Program, Oklahoma Medical Research Foundation, Oklahoma City, Oklahoma, United States of America .
    Waldmann, Laura
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Organismal Biology, Evolution and Developmental Biology.
    Snitting, Daniel
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Organismal Biology, Evolution and Developmental Biology.
    Allalou, Amin
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Science and Technology, Mathematics and Computer Science, Department of Information Technology, Computerized Image Analysis and Human-Computer Interaction.
    Zhang, Hanqing
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Molecular Tools and Functional Genomics.
    Ghanem, Abdurrahman
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Öhman, Caroline
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Materials Science and Engineering, Applied Material Science.
    Dierker, Tabea
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Kjellén, Lena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Burgess, Shawn M.
    Translational and Functional Genomics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland, United States of America .
    Ledin, Johan
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Organismal Biology.
    Chondroitin/dermatan sulfate glycosyltransferase genes are essential for craniofacial development2022In: PLOS Genetics, ISSN 1553-7390, E-ISSN 1553-7404, Vol. 18, no 2, article id e1010067Article in journal (Refereed)
    Abstract [en]

    Chondroitin/dermatan sulfate (CS/DS) proteoglycans are indispensable for animal development and homeostasis but the large number of enzymes involved in their biosynthesis have made CS/DS function a challenging problem to study genetically. In our study, we generated loss-of-function alleles in zebrafish genes encoding CS/DS biosynthetic enzymes and characterized the effect on development in single and double mutants. Homozygous mutants in chsy1, csgalnact1a, csgalnat2, chpfa, ust and chst7, respectively, develop to adults. However, csgalnact1a-/- fish develop distinct craniofacial defects while the chsy1-/- skeletal phenotype is milder and the remaining mutants display no gross morphological abnormalities. These results suggest a high redundancy for the CS/DS biosynthetic enzymes and to further reduce CS/DS biosynthesis we combined mutant alleles. The craniofacial phenotype is further enhanced in csgalnact1a-/-;chsy1-/- adults and csgalnact1a-/-;csgalnact2-/- larvae. While csgalnact1a-/-;csgalnact2-/- was the most affected allele combination in our study, CS/DS is still not completely abolished. Transcriptome analysis of chsy1-/-, csgalnact1a-/- and csgalnact1a-/-;csgalnact2-/- larvae revealed that the expression had changed in a similar way in the three mutant lines but no differential expression was found in any of fifty GAG biosynthesis enzymes identified. Thus, zebrafish larvae do not increase transcription of GAG biosynthesis genes as a consequence of decreased CS/DS biosynthesis. The new zebrafish lines develop phenotypes similar to clinical characteristics of several human congenital disorders making the mutants potentially useful to study disease mechanisms and treatment.

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  • 32. Hedenqvist, Patricia
    et al.
    Trbakovic, Amela
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Plastic Surgery.
    Mellgren, Torbjörn
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - Ångström, Polymer Chemistry.
    Öhman Mägi, Caroline
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Materials Science and Engineering, Applied Material Science.
    Hammarström Johansson, Petra
    Manell, Elin
    Ekman, Stina
    Ley, Cecilia
    Jensen-Waern, Marianne
    Thor, Andreas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Plastic Surgery.
    The effect of housing environment on bone healing in a critical radius defect in New Zealand White rabbits.2020In: PLOS ONE, E-ISSN 1932-6203, Vol. 15, no 5, article id e0233530Article in journal (Refereed)
    Abstract [en]

    In animal studies on bone healing, the effect of housing space and physical activity are seldom taken into account. Bone formation was evaluated in New Zealand White rabbits (mean ± SEM BW: 3.9 ± 0.11 kg) with a critical bone defect after 12 weeks of rehabilitation in pair-housing in 3 m2 large floor pens (Floor, n = 10) or standard single housing in 0.43 m2 cages (Cage, n = 10). In the randomised full-factorial study, a bone replica of calcium phosphate cement (CPC, n = 10) or autologous bone (AB, n = 10) was implanted in the unilateral 20 mm radius defect. Post-mortem, the oxidative capacity was measured by citrate synthase (CS) activity in M. quadriceps and the defect filling volume and density evaluated by microcomputer tomography (μ-CT). Histology sections were evaluated by subjective scoring and histomorphometry. Fourteen rabbits remained until the end of the study. Group Floor (n = 7; 3 CPC + 4 AB) had a higher CS activity and a larger bone defect filling volume and lower density by μ-CT measurements than group Cage (n = 7; 3 CPC + 4 AB). Three out of four rabbits in AB-Floor presented fusion of the defect with reorganisation of trabecular bone, whereas three of four in AB-Cage showed areas of incomplete healing. Floor rabbits had a higher score of bony fusion between the radius and ulna than Cage rabbits. There were no differences between groups in histomorphometry. The study found that a larger housing space increased physical activity and promoted bone formation.

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  • 33. Hedenqvist, Patricia
    et al.
    Trbakovic, Amela
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Oral and Maxillofacial Surgery. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Plastic Surgery.
    Mellgren, Torbjörn
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - Ångström, Polymer Chemistry.
    Öhman Mägi, Caroline
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Materials Science and Engineering, Applied Material Science.
    Hammarström Johansson, Petra
    Manell, Elin
    Ekman, Stina
    Ley, Cecilia
    Jensen-Waern, Marianne
    Thor, Andreas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Oral and Maxillofacial Surgery. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Plastic Surgery.
    The effect of housing environment on bone healing in a critical radius defect in New Zealand White rabbits.2020In: PLOS ONE, E-ISSN 1932-6203, Vol. 15, no 5, article id e0233530Article in journal (Refereed)
    Abstract [en]

    In animal studies on bone healing, the effect of housing space and physical activity are seldom taken into account. Bone formation was evaluated in New Zealand White rabbits (mean ± SEM BW: 3.9 ± 0.11 kg) with a critical bone defect after 12 weeks of rehabilitation in pair-housing in 3 m2 large floor pens (Floor, n = 10) or standard single housing in 0.43 m2 cages (Cage, n = 10). In the randomised full-factorial study, a bone replica of calcium phosphate cement (CPC, n = 10) or autologous bone (AB, n = 10) was implanted in the unilateral 20 mm radius defect. Post-mortem, the oxidative capacity was measured by citrate synthase (CS) activity in M. quadriceps and the defect filling volume and density evaluated by microcomputer tomography (μ-CT). Histology sections were evaluated by subjective scoring and histomorphometry. Fourteen rabbits remained until the end of the study. Group Floor (n = 7; 3 CPC + 4 AB) had a higher CS activity and a larger bone defect filling volume and lower density by μ-CT measurements than group Cage (n = 7; 3 CPC + 4 AB). Three out of four rabbits in AB-Floor presented fusion of the defect with reorganisation of trabecular bone, whereas three of four in AB-Cage showed areas of incomplete healing. Floor rabbits had a higher score of bony fusion between the radius and ulna than Cage rabbits. There were no differences between groups in histomorphometry. The study found that a larger housing space increased physical activity and promoted bone formation.

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  • 34.
    Hulsart-Billstrom, Gry
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Nouhi, Shirin
    Uppsala University, Disciplinary Domain of Science and Technology, Physics, Department of Physics and Astronomy, Materials Physics.
    Larsson, Sune
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Öhman, Caroline
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    Iodine-enhanced contrast applicable for microcomputed tomography2014In: Journal of Tissue Engineering and Regenerative Medicine, ISSN 1932-6254, E-ISSN 1932-7005, Vol. 8, p. 245-246Article in journal (Refereed)
  • 35.
    Hulsart-Billström, Gry
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Öhman, Caroline
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    Österberg, Björn
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Ossipov, Dmitri
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - Ångström, Polymer Chemistry.
    Marsell, Richard
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Larsson, Sune
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    In vivo performance of a BP-linked hyaluronan-based hydrogel as carrier of bone morphogenetic protein-22013Conference paper (Refereed)
  • 36.
    Häggmark, Ilian
    et al.
    Dept. of Applied Physics, KTH Royal Institute of Technology, Stockholm, Sweden.
    Romell, Jenny
    Dept. of Applied Physics, KTH Royal Institute of Technology, Stockholm, Sweden.
    Lewin, Susanne
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    Öhman-Mägi, Caroline
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    Hertz, Hans
    Dept. of Applied Physics, KTH Royal Institute of Technology, Stockholm, Sweden.
    Cellular-Resolution Imaging of Microstructures in Rat Bone using Laboratory Propagation-Based Phase-Contrast X-ray Tomography2018In: Proceedings of the 14th International Conference on X-ray Microscopy (XRM2018), 2018Conference paper (Refereed)
  • 37.
    Jonsson, Henrik
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmacy.
    Öhman-Mägi, Caroline
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    Alderborn, Göran
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmacy.
    Isaksson, Per
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Mechanics.
    Frenning, Göran
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmacy.
    Crack nucleation and propagation in microcrystalline-cellulose based granules subject to uniaxial and triaxial load2019In: International Journal of Pharmaceutics, ISSN 0378-5173, E-ISSN 1873-3476, Vol. 559, p. 130-137Article in journal (Refereed)
    Abstract [en]

    Cracking patterns in four kinds of granules, based on the common pharmaceutical excipient microcrystalline cellulose (MCC) and subject to compressive load, were examined. The initial pore structure and the location of initial failure under uniaxial compression were assessed using X-ray micro-computed tomography, whereas contact force development and onset of cracking under more complex compressive load were examined using a triaxial testing apparatus. Smoothed particle hydrodynamics (SPH) simulations were employed for numerical analysis of the stress distributions prior to cracking. For granules subject to uniaxial compression, initial cracking always occurred along the meridian and the precise location of the crack depended on the pore structure. Likewise, for granules subject to triaxial compression, the fracture plane of the primary crack was generally parallel to the dominant loading direction. The occurrence of cracking was highly dependent on the triaxiality ratio, i.e. the ratio between the punch displacements in the secondary and dominant loading directions. Compressive stresses in the lateral directions, induced by triaxial compression, prevented crack opening and fragmentation of the granule, something that could be verified by simulations. These results provide corroboration as well as further insights into previously observed differences between confined and unconfined compression of granular media.

  • 38.
    Khosravi, Sara.
    et al.
    KTH Royal Institute of Technology.
    Nordqvist, Petra
    AkzoNobel.
    Khabbaz, Farideh
    AkzoNobel.
    Öhman, Caroline
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    Bjurhager, Ingela
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Mechanics.
    Johansson, Mats
    Wetting and film formation of wheat gluten dispersions applied to wood substrates as particle board adhesives2015In: European Polymer Journal, ISSN 0014-3057, E-ISSN 1873-1945, Vol. 67, p. 476-482Article in journal (Refereed)
    Abstract [en]

    The wetting, penetration, and film formation of wheat gluten dispersions on porous wood substrates have been studied using different microscopy techniques. The effect variation of wheat gluten concentration, processing temperatures, dispersion composition, and the application scheme has been studied. The results have been correlated to previously obtained results on the function of wheat gluten dispersions as adhesive binders for particle boards. The results show that the dispersions readily penetrate the porous wood substrate and that the key parameters for a successful gluing are the dispersion viscosity, concentration, and the application scheme. 

  • 39.
    Kotrschal, Alexander
    et al.
    Department of Zoology, Stockholm Univ.
    Zeng, Hong-Li
    Uppsala University, Disciplinary Domain of Science and Technology, Mathematics and Computer Science, Department of Mathematics.
    van der Bijl, Wouter
    Department of Zoology, Stockholm University.
    Öhman-Mägi, Caroline
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    Kotrschal, Kurt
    Department of Behavioural Biology, University of Vienna.
    Pelckmans, Kristiaan
    Uppsala University, Disciplinary Domain of Science and Technology, Mathematics and Computer Science, Department of Mathematics.
    Kolm, Niclas
    Department of Zoology, Stockholm University.
    Evolution of brain region volumes during artificial selection for relative brain size2017In: Evolution, ISSN 0014-3820, E-ISSN 1558-5646, Vol. 71, no 12, p. 2942-2951Article in journal (Refereed)
    Abstract [en]

    The vertebrate brain shows an extremely conserved layout across taxa. Still, the relative sizes of separate brain regions vary markedly between species. One interesting pattern is that larger brains seem associated with increased relative sizes only of certain brain regions, for instance telencephalon and cerebellum. Till now, the evolutionary association between separate brain regions and overall brain size is based on comparative evidence and remains experimentally untested. Here, we test the evolutionary response of brain regions to directional selection on brain size in guppies (Poecilia reticulata) selected for large and small relative brain size. In these animals, artificial selection led to a fast response in relative brain size, while body size remained unchanged. We use microcomputer tomography to investigate how the volumes of 11 main brain regions respond to selection for larger versus smaller brains. We found no differences in relative brain region volumes between large- and small-brained animals and only minor sex-specific variation. Also, selection did not change allometric scaling between brain and brain region sizes. Our results suggest that brain regions respond similarly to strong directional selection on relative brain size, which indicates that brain anatomy variation in contemporary species most likely stem from direct selection on key regions.

  • 40.
    Lewin, Susanne
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    Barba, Albert
    Persson, Cecilia
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    Franch, Jordi
    Ginebra, Maria Pau
    Öhman Mägi, Caroline
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    Assessment of bone formation in CaP scaffolds – µCT method development2017Conference paper (Refereed)
  • 41.
    Lewin, Susanne
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    Barba, Albert
    Autonomous University of Barcelona, Bellaterra, Spain; Technical University of Catalonia, Barcelona, Spain.
    Persson, Cecilia
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    Franch Serracanta, Jordi
    Autonomous University of Barcelona, Bellaterra, Spain.
    Pau Ginebra, Maria
    Technical University of Catalonia, Barcelona, Spain.
    Öhman, Caroline
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    Evaluation of bone formation in calcium phosphate scaffolds with μCT-method validation using SEM2017In: Biomedical Materials, ISSN 1748-6041, E-ISSN 1748-605X, Vol. 12, no 6, article id 065005Article in journal (Refereed)
    Abstract [en]

    There is a plethora of calcium phosphate (CaP) scaffolds used as synthetic substitutes to bone grafts. The scaffold performance is often evaluated from the quantity of bone formed within or in direct contact with the scaffold. Micro-computed tomography (mu CT) allows three-dimensional evaluation of bone formation inside scaffolds. However, the almost identical x-ray attenuation of CaP and bone obtrude the separation of these phases in mu CT images. Commonly, segmentation of bone in mu CT images is based on gray scale intensity, with manually determined global thresholds. However, image analysis methods, and methods for manual thresholding in particular, lack standardization and may consequently suffer from subjectivity. The aim of the present study was to provide a methodological framework for addressing these issues. Bone formation in two types of CaP scaffold architectures (foamed and robocast), obtained from a larger animal study (a 12 week canine animal model) was evaluated by mu CT. In addition, cross-sectional scanning electron microscopy (SEM) images were acquired as references to determine thresholds and to validate the result. mu CT datasets were registered to the corresponding SEM reference. Global thresholds were then determined by quantitatively correlating the different area fractions in the mu CT image, towards the area fractions in the corresponding SEM image. For comparison, area fractions were also quantified using global thresholds determined manually by two different approaches. In the validation the manually determined thresholds resulted in large average errors in area fraction (up to 17%), whereas for the evaluation using SEM references, the errors were estimated to be less than 3%. Furthermore, it was found that basing the thresholds on one single SEM reference gave lower errors than determining them manually. This study provides an objective, robust and less error prone method to determine global thresholds for the evaluation of bone formation in CaP scaffolds.

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  • 42.
    Lewin, Susanne
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Materials Science and Engineering, Applied Material Science.
    Fleps, Ingmar
    Swiss Fed Inst Technol, Inst Biomech, Zurich, Switzerland.
    Neuhaus, Dominique
    Swiss Fed Inst Technol, Inst Biomech, Zurich, Switzerland.
    Öhman, Caroline
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Materials Science and Engineering, Applied Material Science.
    Ferguson, Stephen J.
    Swiss Fed Inst Technol, Inst Biomech, Zurich, Switzerland.
    Persson, Cecilia
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Materials Science and Engineering, Applied Material Science.
    Helgason, Benedikt
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Materials Science and Engineering. Swiss Fed Inst Technol, Inst Biomech, Zurich, Switzerland.
    Implicit and explicit finite element models predict the mechanical response of calcium phosphate-titanium cranial implants2020In: Journal of The Mechanical Behavior of Biomedical Materials, ISSN 1751-6161, E-ISSN 1878-0180, Vol. 112, article id 104085Article in journal (Refereed)
    Abstract [en]

    The structural integrity of cranial implants is of great clinical importance, as they aim to provide cerebral protection after neurosurgery or trauma. With the increased use of patient-specific implants, the mechanical response of each implant cannot be characterized experimentally in a practical way. However, computational models provide an excellent possibility for efficiently predicting the mechanical response of patient-specific implants. This study developed finite element models (FEMs) of titanium-reinforced calcium phosphate (CaP-Ti) implants. The models were validated with previously obtained experimental data for two different CaP-Ti implant designs (D1 and D2), in which generically shaped implant specimens were loaded in compression at either quasi-static (1 mm/min) or impact (5 kg, 1.52 m/s) loading rates. The FEMs showed agreement with experimental data in the force-displacement response for both implant designs.The implicit FEMs predicted the peak load with an underestimation for D1 (9%) and an overestimation for D2 (11%). Furthermore, the shape of the force-displacement curves were well predicted. In the explicit FEMs, the first part of the force-displacement response showed 5% difference for D1 and 2% difference for D2, with respect to the experimentally derived peak loads. The explicit FEMs efficiently predicted the maximum dis-placements with 1% and 4% difference for D1 and D2, respectively. Compared to the CaP-Ti implant, an average parietal cranial bone FEM showed a stiffer response, greater energy absorption and less deformation under the same impact conditions.The framework developed for modelling the CaP-Ti implants has a potential for modelling CaP materials in other composite implants in future studies since it only used literature based input and matched boundary conditions. Furthermore, the developed FEMs make an important contribution to future evaluations of patient specific CaP-Ti cranial implant designs in various loading scenarios.

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  • 43.
    Lewin, Susanne
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Materials Science and Engineering, Applied Material Science.
    Fleps, Ingmar
    ETH Zurich.
    Åberg, Jonas
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Materials Science and Engineering, Applied Material Science.
    Ferguson, Stephen J.
    ETH Zurich.
    Engqvist, Håkan
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Materials Science and Engineering, Applied Material Science.
    Öhman-Mägi, Caroline
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Materials Science and Engineering, Applied Material Science.
    Helgason, Benedikt
    ETH Zurich.
    Persson, Cecilia
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Materials Science and Engineering, Applied Material Science.
    Additively manufactured mesh-type titanium structures for cranial implants: E-PBF vs. L-PBF2021In: Materials & design, ISSN 0264-1275, E-ISSN 1873-4197, Vol. 197, article id 109207Article in journal (Refereed)
    Abstract [en]

    A patient-specific titanium-reinforced calcium phosphate (CaP–Ti) cranial implant has recently shown promising clinical results. Currently, its mesh-type titanium structure is additively manufactured using laser beam powder bed fusion (L-PBF). Nevertheless, an electron-beam (E-PBF) process could potentially be more time efficient. This study aimed to compare the geometrical accuracy and mechanical response of thin titanium structures manufactured by L-PBF (HIPed) and E-PBF (as-printed). Tensile test (ø = 1.2 mm) and implant specimens were manufactured. Measurements by μCT revealed a deviation in cross-sectional area as compared to the designed geometry: 13–35% for E-PBF and below 2% for L-PBF. A superior mechanical strength was obtained for the L-PBF specimens, both in the tensile test and the implant compression tests. The global peak load in the implant test was 457 ± 9 N and 846 ± 40 N for E-PBF and L-PBF, respectively. Numerical simulations demonstrated that geometrical deviation was the main factor in implant performance and enabled quantification of this effect: 34–39% reduction in initial peak force based on geometry, and only 11–16% reduction based on the material input. In summary, the study reveals an uncertainty in accuracy when structures of sizes relevant to mesh-type cranial implants are printed by the E-PBF method.

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  • 44.
    Lewin, Susanne
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    Gallinetti, Sara
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    Kihlström, Lars
    Department of Clinical Neuroscience, Neurosurgical Section, Karolinska University Hospital and Karolinska Institutet, Solna, Sweden.
    Persson, Cecilia
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    Birgersson, Ulrik
    Division of Imaging and Technology, Department of Clinical Science, Intervention and Technology, Karolinska Institutet, Huddinge, Sweden.
    Öhman, Caroline
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    Evaluation of bioactive cranial implants: preliminary results from volumetric quantifications using computed tomography (CT)2018Conference paper (Refereed)
  • 45.
    Lewin, Susanne
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    Gallinetti, Sara
    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.
    Kihlström, Lars
    Department of Clinical Neuroscience, Neurosurgical Section, Karolinska University Hospital and Karolinska Institutet .
    Birgerson, Ulrik
    Div. of Imaging and Technology, Dept. of Clinical Science, Intervention and Technology, Karolinska Institutet.
    Öhman, Caroline
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    Longitudinal assessment of trends in calcium phosphate degradation for cranial implants: preliminary results from two patients2018Conference paper (Refereed)
  • 46.
    Lewin, Susanne
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Materials Science and Engineering, Applied Material Science.
    Linder, Lars Kihlstrom Burenstam
    Karolinska Univ Hosp, Dept Neurosurg, Clin Neurosci, Stockholm, Sweden.;Karolinska Inst, Stockholm, Sweden..
    Birgersson, Ulrik
    Karolinska Univ Hosp, Dept Neurosurg, Clin Neurosci, Stockholm, Sweden.;Karolinska Inst, Stockholm, Sweden.;Karolinska Inst, Div Imaging & Technol, Dept Clin Sci Intervent & Technol, Huddinge, Sweden.;OssDsign, Uppsala, Sweden..
    Gallinetti, Sara
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Materials Science and Engineering, Applied Material Science. OssDsign, Uppsala, Sweden..
    Åberg, Jonas
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Materials Science and Engineering, Applied Material Science. OssDsign, Uppsala, Sweden..
    Engqvist, Håkan
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Materials Science and Engineering, Applied Material Science.
    Persson, Cecilia
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Materials Science and Engineering, Applied Material Science.
    Öhman, Caroline
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Materials Science and Engineering, Applied Material Science.
    Monetite-based composite cranial implants demonstrate long-term clinical volumetric balance by concomitant bone formation and degradation2021In: Acta Biomaterialia, ISSN 1742-7061, E-ISSN 1878-7568, Vol. 128, p. 502-513Article in journal (Refereed)
    Abstract [en]

    The use of calcium phosphates (CaPs) as synthetic bone substitutes should ideally result in a volumetric balance with concomitant bone formation and degradation. Clinical data on such properties is nevertheless lacking, especially for monetite-based CaPs. However, a monetite-based composite implant has recently shown promising cranial reconstructions, with both CaP degradation and bone formation. In this study, the volumetric change at the implant site was quantified longitudinally by clinical computed tomography (CT). The retrospective CT datasets had been acquired postoperatively ( n = 10), in 1-year ( n = 9) and 3-year ( n = 5) follow-ups. In the 1-year follow-up, the total volumetric change at the implant site was-8 +/- 8%. A volumetric increase (bone formation) was found in the implant-bone interface, and a volumetric decrease was observed in the central region (CaP degradation). In the subjects with 2-or 3-year follow-ups, the rate of volumetric decrease slowed down or plateaued. The reported degradation rate is lower than previous clinical studies on monetite, likely due to the presence of pyrophosphate in the monetite-based CaP-formulation. A 31-months retrieval specimen analysis demonstrated that parts of the CaP had been remodeled into bone. The CaP phase composition remained stable, with 6% transformation into hydroxyapatite. In conclusion, this study demonstrates successful bone-bonding between the CaP-material and the recipient bone, as well as a long-term volumetric balance in cranial defects repaired with the monetitebased composite implant, which motivates further clinical use. The developed methods could be used in future studies for correlating spatiotemporal information regarding bone regeneration and CaP degradation to e.g. patient demographics. Statement of significance In bone defect reconstructions, the use of calcium phosphate (CaP) bioceramics ideally results in a volumetric balance between bone formation and CaP degradation. Clinical data on the volumetric balance is nevertheless lacking, especially for monetite-based CaPs. Here, this concept is investigated for a composite cranial implant. The implant volumes were quantified from clinical CT-data: postoperatively, one year and three years postoperatively. In total,-8 +/- 8% ( n = 9) volumetric change was observed after one year. But the change plateaued, with only 2% additional decrease at the 3-year follow-up ( n = 5), indicating a lower CaP degradation rate. Osseointegration was seen at the bone-implant interface, with a 9 +/- 7% volumetric change after one year. This study presented the first quantitative spatiotemporal CT analysis of monetite-based CaPs.

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  • 47.
    Lewin, Susanne
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    Riben, Christopher
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Oral and Maxillofacial Surgery.
    Thor, Andreas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Oral and Maxillofacial Surgery.
    Öhman, Caroline
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    Bone Volume Assessment Around Dental Implants After Open Maxillary Sinus Elevation Surgery: A Quantitative Approach to CBCT Images2019In: International Journal of Oral & Maxillofacial Implants, ISSN 0882-2786, E-ISSN 1942-4434, Vol. 34, no 2, p. 489-498, article id 30716145Article in journal (Refereed)
    Abstract [en]

    Purpose: Cone beam computed tomography (CBCT) is an important imaging technique in maxillofacial evaluations. However, application-specific image analysis methods aimed at extracting quantitative information from these images need to be further developed. The aim of this study was to provide a robust and objective method that could assess radiologic changes around dental implants after sinus elevation surgery with simultaneous implant placement.

    Materials and Methods: The study was performed retrospectively on patients fulfilling the inclusion criteria. The included patients had been CBCT scanned preoperatively, at baseline (early after surgery), and 6 months postoperatively. In order to quantify the radiologic changes, an image analysis workflow was developed based on the postoperative baseline and 6-month scans. The workflow included metal artifact reduction, registration, and a standardized protocol for semiautomatic segmentation. Validation of different steps of the method was conducted by comparing scans from all time points. Comparison of constant volumes (eg, screws and bony parts not subjected to change) was used. Additionally, the Dice similarity coefficient (DSC) was used to measure the overlap of the segmentations.

    Results: The study included nine maxillary sinuses from six patients. The bone formation was quantified and visualized in 3D. In the validation, no significant differences were found for the constant volumes at the different scanning time points. The DSC showed accurate results with values > 0.92.

    Conclusion: The method presented in this study provides an objective and robust evaluation of bone formation around dental implants. The same methodologies can be applied in other studies of dental CBCT images, eg, for comparison of grafting materials or surgical strategies.

  • 48.
    Lewin, Susanne
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Materials Science and Engineering, Applied Material Science.
    Riben, Christopher
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Oral and Maxillofacial Surgery.
    Thor, Andreas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Oral and Maxillofacial Surgery.
    Öhman-Mägi, Caroline
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Materials Science and Engineering, Applied Material Science.
    Bone Volume Assessment Around Dental Implants After Open Maxillary Sinus Elevation Surgery: A Quantitative Approach to CBCT Images2019In: International Journal of Oral & Maxillofacial Implants, ISSN 0882-2786, E-ISSN 1942-4434, Vol. 34, no 2, p. 489-498Article in journal (Refereed)
    Abstract [en]

    Purpose: Cone beam computed tomography (CBCT) is an important imaging technique in maxillofacialevaluations. However, application-specific image analysis methods aimed at extracting quantitativeinformation from these images need to be further developed. The aim of this study was to provide a robust andobjective method that could assess radiologic changes around dental implants after sinus elevation surgerywith simultaneous implant placement. Materials and Methods: The study was performed retrospectivelyon patients fulfilling the inclusion criteria. The included patients had been CBCT scanned preoperatively,at baseline (early after surgery), and 6 months postoperatively. In order to quantify the radiologic changes,an image analysis workflow was developed based on the postoperative baseline and 6-month scans. Theworkflow included metal artifact reduction, registration, and a standardized protocol for semiautomaticsegmentation. Validation of different steps of the method was conducted by comparing scans from all timepoints. Comparison of constant volumes (eg, screws and bony parts not subjected to change) was used.Additionally, the Dice similarity coefficient (DSC) was used to measure the overlap of the segmentations.Results: The study included nine maxillary sinuses from six patients. The bone formation was quantifiedand visualized in 3D. In the validation, no significant differences were found for the constant volumes atthe different scanning time points. The DSC showed accurate results with values > 0.92. Conclusion:The method presented in this study provides an objective and robust evaluation of bone formation arounddental implants. The same methodologies can be applied in other studies of dental CBCT images, eg, forcomparison of grafting materials or surgical strategies.

  • 49.
    Lewin, Susanne
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    Riben, Christopher
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Oral and Maxillofacial Surgery.
    Thor, Andreas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Plastic Surgery.
    Öhman-Mägi, Caroline
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    Quantification of radiological changes around dental implants:: a CBCT image analysis2017Conference paper (Refereed)
  • 50.
    Lewin, Susanne
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Materials Science and Engineering, Applied Material Science.
    Åberg, Jonas
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Materials Science and Engineering, Applied Material Science.
    Neuhaus, Dominique
    Institute for Biomechanics, ETH Zurich, Zurich, Switzerland.
    Engqvist, Håkan
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Materials Science and Engineering, Applied Material Science.
    Ferguson, Stephen J.
    Institute for Biomechanics, ETH Zurich, Zurich, Switzerland.
    Öhman, Caroline
    Helgason, Benedikt
    Institute for Biomechanics, ETH Zurich, Zurich, Switzerland.
    Persson, Cecilia
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Materials Science and Engineering, Applied Material Science.
    Mechanical behaviour of composite calcium phosphate-titanium cranial implants: Effects of loading rate and design2020In: Journal of The Mechanical Behavior of Biomedical Materials, ISSN 1751-6161, E-ISSN 1878-0180, Vol. 104, article id 103701Article in journal (Refereed)
    Abstract [en]

    Cranial implants are used to repair bone defects following neurosurgery or trauma. At present, there is a lack of data on their mechanical response, particularly in impact loading. The aim of the present study was to assess the mechanical response of a recently developed composite calcium phosphate-titanium (CaP-Ti) implant at quasi-static and impact loading rates. Two different designs were tested, referred to as Design 1 (D1) and Design 2 (D2). The titanium structures in the implant specimens were additively manufactured by a powder-bed fusion process and subsequently embedded in a self-setting CaP material. D1 was conceptually representative of the clinically used implants. In D2, the titanium structure was simplified in terms of geometry in order to facilitate the manufacturing. The mechanical response of the implants was evaluated in quasi-static compression, and in impact using a drop-tower. Similar peak loads were obtained for the two designs, at the two loading rates: 808 ± 29 N and 852 ± 34 for D1, and 840 ± 40 N and 814 ± 13 for D2. A strain rate dependency was demonstrated for both designs, with a higher stiffness in the impact test. Furthermore, the titanium in the implant fractured in the quasi-static test (to failure) but not in the impact test (to 5.75 J) for D1. For D2, the displacement at peak load was significantly lower in the impact test than in the quasi-static test. The main difference between the designs was seen in the quasi-static test results where the deformation zones, i.e. notches in the titanium structure between the CaP tiles, in D1 likely resulted in a localization of the deformation, compared to in D2 (which did not have deformation zones). In the impact test, the only significant difference between the designs was a higher maximum displacement of D2 than of D1. In comparison with other reported mechanical tests on osteoconductive ceramic-based cranial implants, the CaP-Ti implant demonstrates the highest reported strength in quasi-static compression. In conclusion, the titanium structure seems to make the CaP-Ti implant capable of cerebral protection in impact situations like the one tested in this study.

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