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Mellgren, T., Qin, T., Öhman Mägi, C., Zhang, Y., Wu, B., Xia, W. & Engqvist, H. (2018). Calcium Phosphate Microspheres as a Delivery Vehicle for Tooth-Bleaching Agents. Journal of Dental Research, 97(3), 283-288
Open this publication in new window or tab >>Calcium Phosphate Microspheres as a Delivery Vehicle for Tooth-Bleaching Agents
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2018 (English)In: Journal of Dental Research, ISSN 0022-0345, E-ISSN 1544-0591, Vol. 97, no 3, p. 283-288Article in journal (Refereed) Published
Abstract [en]

Bleaching of vital teeth has become common practice in cosmetic dentistry today. Tooth sensitivity and demineralization of the enamel are, however, common side effects associated with hydrogen and carbamide peroxide bleaching. This study investigated if calcium phosphate microspheres, which have remineralizing properties, could be used as an additive without hindering the diffusion of the bleaching agent and if the spheres could be used as a carrier for carbamide peroxide. A remineralizing agent could increase the safety of bleaching and decrease the severity of its side effects. Comparisons between current hydrogen peroxide diffusion studies and previously published work are difficult since many studies include challenging-to-replicate conditions or lack reporting of important parameters. Hence, a diffusion model was designed by Wu Lab (School of Dentistry, University of California, Los Angeles) to measure the diffusion flux and determine the diffusivity of hydrogen peroxide. Physical parameters (e.g., diffusivity) could then be used for direct comparison to the results obtained by future studies. Three whitening gels with increasing amounts of spheres were formulated and tested with 2 commercially available whitening gels. The flux of hydrogen peroxide through 1-mm discs of bovine enamel was measured at steady-state conditions, and the diffusivity was calculated. The results showed that the spheres could be used as a carrier for carbamide peroxide and that the amount of spheres did not affect the diffusivity of peroxide through the enamel discs. Hence, the microspheres are considered promising as an additive to minimize side effects in bleaching gel formulation.

Place, publisher, year, edition, pages
SAGE PUBLICATIONS INC, 2018
Keywords
dental enamel, diffusion, peroxide, tooth whitening, tooth sensitivity, tooth remineralization
National Category
Dentistry Engineering and Technology
Identifiers
urn:nbn:se:uu:diva-352988 (URN)10.1177/0022034517741295 (DOI)000429319800006 ()29125909 (PubMedID)
Funder
Swedish Research Council, 20135419
Available from: 2018-07-17 Created: 2018-07-17 Last updated: 2018-07-25Bibliographically approved
Robo, C., Öhman, C. & Persson, C. (2018). Compressive fatigue properties of commercially available standard and low-modulus acrylic bone cements intended for vertebroplasty. Journal of The Mechanical Behavior of Biomedical Materials, 82, 70-76
Open this publication in new window or tab >>Compressive fatigue properties of commercially available standard and low-modulus acrylic bone cements intended for vertebroplasty
2018 (English)In: Journal of The Mechanical Behavior of Biomedical Materials, ISSN 1751-6161, E-ISSN 1878-0180, Vol. 82, p. 70-76Article in journal (Refereed) Published
Abstract [en]

Vertebroplasty (VP) is a minimally invasive surgical procedure commonly used to relieve severe back pain associated with vertebral compression fractures. The poly(methyl methacrylate) bone cement used during this procedure is however presumed to facilitate the occurrence of additional fractures next to the treated vertebrae. A reason for this is believed to be the difference in stiffness between the bone cement and the surrounding trabecular bone. The use of bone cements with lower mechanical properties could therefore reduce the risk of complications post-surgery. While intensive research has been performed on the quasi-static mechanical properties of these cements, there is no data on their long-term mechanical properties. In the present study, the in vitrocompressive fatigue performance as well as quasi-static mechanical properties of two commercially available acrylic bone cements - a low-modulus cement (Resilience®) and a standard cement (F20) from the same manufacturer - were determined. The quasi-static mechanical properties of the low-modulus and standard cements after 24h of setting were in the range of other vertebroplastic cements (σ=70-75 MPa; E=1600-1900 MPa). F20 displayed similar mechanical properties over time in 37˚C phosphate buffered saline solution, while the mechanical properties of the Resilience®cement decreased gradually due to an increased porosity in the polymeric matrix. The standard cement exhibited a fatigue limit of approx. 47 MPa, whereas the low-modulus cement showed a fatigue limit of approx. 31 MPa. 

In summary, the low-modulus bone cement had a lower fatigue limit than the standard cement, as expected. However, this fatigue limit is still substantially higher than the stresses experienced by vertebral trabecular bone.  

Place, publisher, year, edition, pages
Elsevier, 2018
Keywords
Acrylic bone cement, low-modulus, elastic modulus, compression, fatigue, vertebroplasty
National Category
Other Materials Engineering
Research subject
Engineering Science with specialization in Materials Science
Identifiers
urn:nbn:se:uu:diva-349032 (URN)10.1016/j.jmbbm.2018.03.001 (DOI)000432508800009 ()
Funder
The Royal Swedish Academy of Sciences, FOA13H-141
Available from: 2018-04-20 Created: 2018-04-20 Last updated: 2018-08-02Bibliographically approved
Sladkova, M., Pujari-Palmer, M., Öhman, C., Cheng, J., Al-Ansari, S., Saad, M., . . . de Peppo, G. M. (2018). Engineering human bone grafts with new macroporous calcium phosphate cement scaffolds. Journal of Tissue Engineering and Regenerative Medicine, 12(3), 715-726
Open this publication in new window or tab >>Engineering human bone grafts with new macroporous calcium phosphate cement scaffolds
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2018 (English)In: Journal of Tissue Engineering and Regenerative Medicine, ISSN 1932-6254, E-ISSN 1932-7005, Vol. 12, no 3, p. 715-726Article in journal (Refereed) Published
Abstract [en]

Bone engineering opens the possibility to grow large amounts of tissue products by combining patient-specific cells with compliant biomaterials. Decellularized tissue matrices represent suitable biomaterials, but availability, long processing time, excessive cost, and concerns on pathogen transmission have led to the development of biomimetic synthetic alternatives. We recently fabricated calcium phosphate cement (CPC) scaffolds with variable macroporosity using a facile synthesis method with minimal manufacturing steps and demonstrated long-term biocompatibility in vitro. However, there is no knowledge on the potential use of these scaffolds for bone engineering and whether the porosity of the scaffolds affects osteogenic differentiation and tissue formation in vitro. In this study, we explored the bone engineering potential of CPC scaffolds with two different macroporosities using human mesenchymal progenitors derived from induced pluripotent stem cells (iPSC-MP) or isolated from bone marrow (BMSC). Biomimetic decellularized bone scaffolds were used as reference material in all experiments. The results demonstrate that, irrespective of their macroporosity, the CPC scaffolds tested in this study support attachment, viability, and growth of iPSC-MP and BMSC cells similarly to decellularized bone. Importantly, the tested materials sustained differentiation of the cells as evidenced by increased expression of osteogenic markers and formation of a mineralized tissue. In conclusion, the results of this study suggest that the CPC scaffolds fabricated using our method are suitable to engineer bone grafts from different cell sources and could lead to the development of safe and more affordable tissue grafts for reconstructive dentistry and orthopaedics and in vitro models for basic and applied research.

National Category
Other Medical Engineering
Research subject
Engineering Science with specialization in Materials Science
Identifiers
urn:nbn:se:uu:diva-335996 (URN)10.1002/term.2491 (DOI)000427137100061 ()28635177 (PubMedID)
Funder
EU, FP7, Seventh Framework Programme
Available from: 2017-12-11 Created: 2017-12-11 Last updated: 2018-06-04Bibliographically approved
Ajaxon, I., Holmberg, A., Öhman, C. & Persson, C. (2018). Fatigue performance of a high-strength, degradable calcium phosphate bone cement. Journal of The Mechanical Behavior of Biomedical Materials, 79, 46-52
Open this publication in new window or tab >>Fatigue performance of a high-strength, degradable calcium phosphate bone cement
2018 (English)In: Journal of The Mechanical Behavior of Biomedical Materials, ISSN 1751-6161, E-ISSN 1878-0180, Vol. 79, p. 46-52Article in journal (Refereed) Published
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.

Place, publisher, year, edition, pages
ELSEVIER SCIENCE BV, 2018
Keywords
Bone cement, Calcium phosphate, Brushite, Fatigue, Compression, Porosity, Mechanical properties
National Category
Medical Materials
Identifiers
urn:nbn:se:uu:diva-347539 (URN)10.1016/j.jmbbm.2017.12.005 (DOI)000425072300006 ()29272812 (PubMedID)
Funder
Swedish Research Council, 621-2011-6258
Available from: 2018-04-04 Created: 2018-04-04 Last updated: 2018-04-09Bibliographically approved
Ajaxon, I., Öhman Mägi, C. & Persson, C. (2017). Compressive fatigue properties of an acidic calcium phosphate cement—effect of phase composition. Journal of materials science. Materials in medicine, 28(3), Article ID 41.
Open this publication in new window or tab >>Compressive fatigue properties of an acidic calcium phosphate cement—effect of phase composition
2017 (English)In: Journal of materials science. Materials in medicine, ISSN 0957-4530, E-ISSN 1573-4838, Vol. 28, no 3, article id 41Article in journal (Refereed) Published
Abstract [en]

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

Keywords
Bone cement, brushite, monetite, fatigue, mechanical properties
National Category
Ceramics Medical Materials Biomaterials Science
Research subject
Engineering Science with specialization in Materials Science
Identifiers
urn:nbn:se:uu:diva-314237 (URN)10.1007/s10856-017-5851-5 (DOI)000394242700006 ()28144853 (PubMedID)
Funder
Swedish Research Council, 621-2011-6258
Available from: 2017-02-03 Created: 2017-01-31 Last updated: 2017-11-29Bibliographically approved
Wu, D., Joffre, T., Gallinetti, S., Öhman Mägi, C., Ferguson, S. J., Isaksson, P. & Persson, C. (2017). Elastic Modulus Of Human Single Trabeculae Estimated by Synchrotron CT Experiments And Numerical Models. In: : . Paper presented at 23rd Congress of the European Society of Biomechanics, Seville, 2-5 July,2017.
Open this publication in new window or tab >>Elastic Modulus Of Human Single Trabeculae Estimated by Synchrotron CT Experiments And Numerical Models
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2017 (English)Conference paper, Oral presentation with published abstract (Refereed)
National Category
Other Biological Topics Materials Engineering
Research subject
Engineering Science with specialization in Materials Science
Identifiers
urn:nbn:se:uu:diva-333080 (URN)
Conference
23rd Congress of the European Society of Biomechanics, Seville, 2-5 July,2017
Available from: 2017-11-06 Created: 2017-11-06 Last updated: 2017-12-29Bibliographically approved
Ajaxon, I., Acciaioli, A., Lionello, G., Ginebra, M.-P., Öhman, C., Baleani, M. & Persson, C. (2017). Elastic properties and strain-to-crack-initation of calcium phosphate bone cements: Revelations of a high-resolution measurement technique. Journal of The Mechanical Behavior of Biomedical Materials, 74, 428-437
Open this publication in new window or tab >>Elastic properties and strain-to-crack-initation of calcium phosphate bone cements: Revelations of a high-resolution measurement technique
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2017 (English)In: Journal of The Mechanical Behavior of Biomedical Materials, ISSN 1751-6161, E-ISSN 1878-0180, Vol. 74, p. 428-437Article in journal (Refereed) Published
Abstract [en]

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

National Category
Ceramics Medical Materials Biomaterials Science
Identifiers
urn:nbn:se:uu:diva-316718 (URN)10.1016/j.jmbbm.2017.06.023 (DOI)000410253500046 ()28735216 (PubMedID)
Funder
The Swedish Foundation for International Cooperation in Research and Higher Education (STINT), IG2011-2047Swedish Research Council, 621-2011-6258
Available from: 2017-03-22 Created: 2017-03-22 Last updated: 2017-12-04Bibliographically approved
Lewin, S., Barba, A., Persson, C., Franch Serracanta, J., Pau Ginebra, M. & Öhman, C. (2017). Evaluation of bone formation in calcium phosphate scaffolds with μCT-method validation using SEM. Biomedical Materials, 12(6), Article ID 065005.
Open this publication in new window or tab >>Evaluation of bone formation in calcium phosphate scaffolds with μCT-method validation using SEM
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2017 (English)In: Biomedical Materials, ISSN 1748-6041, E-ISSN 1748-605X, Vol. 12, no 6, article id 065005Article in journal (Refereed) Published
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.

Place, publisher, year, edition, pages
Institute of Physics (IOP), 2017
Keywords
Calcium phosphate scaffolds, micro computed tomography, bone formation, image analysis, segmentation
National Category
Biomaterials Science Engineering and Technology
Research subject
Engineering Science with specialization in Materials Science
Identifiers
urn:nbn:se:uu:diva-330518 (URN)10.1088/1748-605X/aa801d (DOI)000412438700002 ()28714854 (PubMedID)
Funder
The Swedish Foundation for International Cooperation in Research and Higher Education (STINT), IG2011-2047
Available from: 2017-10-02 Created: 2017-10-02 Last updated: 2018-08-06Bibliographically approved
Kotrschal, A., Zeng, H.-L., van der Bijl, W., Öhman-Mägi, C., Kotrschal, K., Pelckmans, K. & Kolm, N. (2017). Evolution of brain region volumes during artificial selection for relative brain size. Evolution, 71(12), 2942-2951
Open this publication in new window or tab >>Evolution of brain region volumes during artificial selection for relative brain size
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2017 (English)In: Evolution, ISSN 0014-3820, E-ISSN 1558-5646, Vol. 71, no 12, p. 2942-2951Article in journal (Refereed) Published
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.

National Category
Evolutionary Biology Engineering and Technology
Identifiers
urn:nbn:se:uu:diva-335997 (URN)10.1111/evo.13373 (DOI)000417567000013 ()28986929 (PubMedID)
Funder
Knut and Alice Wallenberg Foundation, 102 2013.0072
Available from: 2017-12-11 Created: 2017-12-11 Last updated: 2018-03-08Bibliographically approved
Lind, T., Öhman, C., Calounova, G., Rasmusson, A., Andersson, G., Pejler, G. & Melhus, H. (2017). Excessive dietary intake of vitamin A reduces skull bone thickness in mice. PLoS ONE, 12(4), Article ID e0176217.
Open this publication in new window or tab >>Excessive dietary intake of vitamin A reduces skull bone thickness in mice
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2017 (English)In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 12, no 4, article id e0176217Article in journal (Refereed) Published
Abstract [en]

Calvarial thinning and skull bone defects have been reported in infants with hypervitaminosis A. These findings have also been described in humans, mice and zebrafish with loss-of-function mutations in the enzyme CYP26B1 that degrades retinoic acid (RA), the active metabolite of vitamin A, indicating that these effects are indeed caused by too high levels of vitamin A and that evolutionary conserved mechanisms are involved. To explore these mechanisms, we have fed young mice excessive doses of vitamin A for one week and then analyzed the skull bones using micro computed tomography, histomorphometry, histology and immunohistochemistry. In addition, we have examined the effect of RA on gene expression in osteoblasts in vitro. Compared to a standard diet, a high dietary intake of vitamin A resulted in a rapid and significant reduction in calvarial bone density and suture diastasis. The bone formation rate was almost halved. There was also increased staining of tartrate resistant acid phosphatase in osteocytes and an increased perilacunar matrix area, indicating osteocytic osteolysis. Consistent with this, RA induced genes associated with bone degradation in osteoblasts in vitro. Moreover, and in contrast to other known bone resorption stimulators, vitamin A induced osteoclastic bone resorption on the endocranial surfaces.

National Category
Clinical Medicine Engineering and Technology
Identifiers
urn:nbn:se:uu:diva-322801 (URN)10.1371/journal.pone.0176217 (DOI)000399875900119 ()28426756 (PubMedID)
Available from: 2017-09-12 Created: 2017-09-12 Last updated: 2017-11-29Bibliographically approved
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ORCID iD: ORCID iD iconorcid.org/0000-0003-2709-9541

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