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Pujari-Palmer, M., Robo, C., Persson, C., Procter, P. & Engqvist, H. (2018). Influence of cement compressive strength and porosity on augmentation performance in a model of orthopedic screw pull-out. Journal of The Mechanical Behavior of Biomedical Materials, 77, 624-633.
Open this publication in new window or tab >>Influence of cement compressive strength and porosity on augmentation performance in a model of orthopedic screw pull-out
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2018 (English)In: Journal of The Mechanical Behavior of Biomedical Materials, ISSN 1751-6161, E-ISSN 1878-0180, Vol. 77, p. 624-633Article in journal (Refereed) Published
Abstract [en]

Disease and injuries that affect the skeletal system may require surgical intervention and internal fixation, i.e. orthopedic plate and screw insertion, to stabilize the injury and facilitate tissue repair. If the surrounding bone quality is poor the screws may migrate, or the bone may fail, resulting in screw pull-out. Though numerous studies have shown that cement augmentation of the interface between bone and implant can increase screw holding strength in bone, the physical properties of cement that influence pull-out force have not been investigated. The present study sought to determine how the physical properties of calcium phosphate cements (CPCs), and the strength of the biological or synthetic material surrounding the augmented screw, affected the corresponding orthopedic screw pull-out force in urethane foam models of healthy and osteoporotic bone (Sawbones). In the simplest model, where only the bond strength between screw thread and cement (without Sawbone) was tested, the correlation between pull-out force and cement compressive strength (R2 = 0.79) was weaker than correlation with total cement porosity (R2 = 0.89). In open pore Sawbone that mimics “healthy” cancellous bone density the stronger cements produced higher pull-out force (50-60% increase). Higher strength, lower porosity, cements also produced higher pull-out forces (50-190% increase) in Sawbones with cortical fixation if the failure strength of the cortical material was similar to (bovine tibial bone), or greater than (metal shell), actual cortical bone. This result is of particular clinical relevance where fixation with a metal plate implant is indicated, as the nearby metal can simulate a thicker cortical shell and, thereby, increase the pull-out force of screws augmented with stronger cements. The improvement in pull-out force was apparent even at low augmentation volumes of 0.5 ml (50% increase), which suggest that in clinical situations where augmentation volume is limited the stronger, lower porosity CPCs may still produce a significant improvement in screw holding strength. When correlations of all the tested models were compared both cement porosity and compressive strength accurately predicted pull-out force (R2=1.00, R2=0.808), though prediction accuracy depended upon the strength of the material surrounding the Sawbone. The correlations strength was low for bone with no, or weak, cortical fixation. Higher strength and lower porosity CPCs also produced greater pull-out force (1-1.5 kN) than commercial CPC (0.2-0.5kN), but lower pull-out force than PMMA (2-3 kN). The results of this study suggest that the likelihood of screw fixation failure may be reduced by selecting calcium phosphate cements with lower porosity and higher bulk strength, in patients with healthy bone mineral density and/or sufficient cortical thickness. This is of particular clinical relevance when fixation with metal plates is indicated, or where the augmentation volume is limited.

Place, publisher, year, edition, pages
Elsevier, 2018
Keyword
Screw pull-out, Orthopedic screw augmentation, Calcium phosphate cement, Bioceramic, Bone biomechanics, Sawbones, Cortical fixation
National Category
Medical Materials Ceramics Applied Mechanics Biomaterials Science
Research subject
Engineering Science with specialization in Materials Science
Identifiers
urn:nbn:se:uu:diva-320157 (URN)10.1016/j.jmbbm.2017.10.016 (DOI)000418309500073 ()29100205 (PubMedID)
Funder
Swedish Research Council, 621–2011-3399EU, FP7, Seventh Framework Programme, 262948
Available from: 2017-04-16 Created: 2017-04-16 Last updated: 2018-02-16Bibliographically approved
Gallinetti, S., Mestres, G., Canal, C., Persson, C. & Ginebra, M.-P. (2017). A novel strategy to enhance interfacial adhesion in fiber-reinforced calcium phosphate cement. Journal of The Mechanical Behavior of Biomedical Materials, 75, 495-503.
Open this publication in new window or tab >>A novel strategy to enhance interfacial adhesion in fiber-reinforced calcium phosphate cement
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2017 (English)In: Journal of The Mechanical Behavior of Biomedical Materials, ISSN 1751-6161, E-ISSN 1878-0180, Vol. 75, p. 495-503Article in journal (Refereed) Published
Abstract [en]

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

Keyword
Calcium phosphate cement; Chitosan; Fiber reinforced; Interfacial adhesion; Toughness; Work of fracture
National Category
Biomaterials Science Engineering and Technology
Identifiers
urn:nbn:se:uu:diva-328681 (URN)10.1016/j.jmbbm.2017.08.017 (DOI)000412959000055 ()28841545 (PubMedID)
Funder
EU, FP7, Seventh Framework Programme, 241879; IG2011-2047VINNOVA, 2013-01260Lars Hierta Memorial Foundation, FO2014-0334
Available from: 2017-08-29 Created: 2017-08-29 Last updated: 2018-02-19Bibliographically 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. 

Keyword
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
National Category
Biomaterials Science Engineering and Technology
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: 2018-02-02
Skjöldebrand, C., Schmidt, S., Vuong, V., Pettersson, M., Grandfield, K., Hogberg, H., . . . Persson, C. (2017). Influence of Substrate Heating and Nitrogen Flow on the Composition, Morphological and Mechanical Properties of SiNx Coatings Aimed for Joint Replacements. Materials, 10(2).
Open this publication in new window or tab >>Influence of Substrate Heating and Nitrogen Flow on the Composition, Morphological and Mechanical Properties of SiNx Coatings Aimed for Joint Replacements
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2017 (English)In: Materials, ISSN 1996-1944, E-ISSN 1996-1944, Vol. 10, no 2Article in journal (Refereed) Published
Abstract [en]

Silicon nitride (SiNx) coatings are promising for joint replacement applications due to their high wear resistance and biocompatibility. For such coatings, a higher nitrogen content, obtained through an increased nitrogen gas supply, has been found to be beneficial in terms of a decreased dissolution rate of the coatings. The substrate temperature has also been found to affect the composition as well as the microstructure of similar coatings. The aim of this study was to investigate the effect of the substrate temperature and nitrogen flow on the coating composition, microstructure and mechanical properties. SiNx coatings were deposited onto CoCrMo discs using reactive high power impulse magnetron sputtering. During deposition, the substrate temperatures were set to 200 degrees C, 350 degrees C or 430 degrees C, with nitrogen-to-argon flow ratios of 0.06, 0.17 or 0.30. Scanning and transmission electron spectroscopy revealed that the coatings were homogenous and amorphous. The coatings displayed a nitrogen content of 23-48 at.% (X-ray photoelectron spectroscopy). The surface roughness was similar to uncoated CoCrMo (p = 0.25) (vertical scanning interferometry). The hardness and Young's modulus, as determined from nanoindentation, scaled with the nitrogen content of the coatings, with the hardness ranging from 12 +/- 1 GPa to 26 +/- 2 GPa and the Young's moduli ranging from 173 +/- 8 GPa to 293 +/- 18 GPa, when the nitrogen content increased from 23% to 48%. The low surface roughness and high nano-hardness are promising for applications exposed to wear, such as joint implants.

Place, publisher, year, edition, pages
MDPI AG, 2017
Keyword
silicon nitride, coating, hip joint replacement, X-ray photoelectron spectroscopy (XPS), nanoindentation, hardness, Young's modulus, transmission electron microscopy (TEM)
National Category
Materials Engineering
Identifiers
urn:nbn:se:uu:diva-320778 (URN)10.3390/ma10020173 (DOI)000395445800080 ()
Funder
EU, FP7, Seventh Framework Programme, GA-310477Carl Tryggers foundation , CTS 14:431
Available from: 2017-04-25 Created: 2017-04-25 Last updated: 2017-11-29Bibliographically approved
Luo, J., Martinez-Casado, F. J., Balmes, O., Yang, J., Persson, C., Engqvist, H. & Xia, W. (2017). In-situ Synchrotron X-ray Diffraction Analysis of the Setting Process of Brushite Cement: Reaction and Crystal Growth. ACS Applied Materials and Interfaces, 9(41), 36392-36399.
Open this publication in new window or tab >>In-situ Synchrotron X-ray Diffraction Analysis of the Setting Process of Brushite Cement: Reaction and Crystal Growth
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2017 (English)In: ACS Applied Materials and Interfaces, ISSN 1944-8244, E-ISSN 1944-8252, Vol. 9, no 41, p. 36392-36399Article in journal (Refereed) Published
Abstract [en]

Brushite cements are fast self-setting materials that can be used as bone substitute materials. Although tracing their fast setting process is a challenge, it is important for the understanding of the same, which in turn is important for the material’s further development and use in the clinics. In this study, the setting rate, phase formation, and crystal growth of brushite cements were quantitatively studied by in situ synchrotron powder X-ray diffraction (SXRD) on a time scale of seconds. The influence of reactant ratios and a retardant (citric acid) on the setting reaction were analyzed. To complement the in situ investigations, scanning electron microscopy was carried out for ex situ morphological evolution of crystals. The initial reaction followed a four-step process, including a fast nucleation induction period, nucleation, crystal growth, and completion of the setting. The brushite crystal size grew up to the micro scale within 1 min, and the brushite content increased linearly after the nucleation until all monocalcium phosphate monohydrate (MCPM; Ca(H2PO4)2·H2O) had dissolved within minutes, followed by a slow increase until the end of the monitoring. By adjusting the MCPM to the β-tricalcium phosphate (β-TCP, β-Ca3(PO4)2) ratio in the starting powders, the brushite/monetite ratio in the cements could be modified. In the presence of citric acid, the formation of brushite nuclei was not significantly retarded, whereas the increase in brushite content and the growth of crystal size were effectively hindered. The amount of monetite also increased by adding citric acid. This is the first time that the brushite setting process has been characterized in the first seconds and minutes of the reaction by SXRD.

Keyword
synchrotron X-ray diffraction, setting reaction process, brushite cement, crystal size, citric acid, MCPM/β-TCP ratio
National Category
Engineering and Technology Medical Materials Biomaterials Science
Research subject
Engineering Science with specialization in Materials Science
Identifiers
urn:nbn:se:uu:diva-330146 (URN)10.1021/acsami.7b10159 (DOI)000413503700092 ()
Available from: 2017-09-26 Created: 2017-09-26 Last updated: 2018-02-08Bibliographically approved
Shah, F., Lee, B., Tedesco, J., Larsson Wexell, C., Persson, C., Thomsen, P., . . . Palmquist, A. (2017). Micrometre-sized magnesium whitlockite crystals in micropetrosis of bisphosphonate-exposed human alveolar bone. Nano letters (Print), 17(10), 6210-6216.
Open this publication in new window or tab >>Micrometre-sized magnesium whitlockite crystals in micropetrosis of bisphosphonate-exposed human alveolar bone
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2017 (English)In: Nano letters (Print), ISSN 1530-6984, E-ISSN 1530-6992, Vol. 17, no 10, p. 6210-6216Article in journal (Refereed) Published
Abstract [en]

Osteocytes are contained within spaces called lacunae and play a central role in bone remodelling. Administered frequently to prevent osteoporotic fractures, antiresorptive agents such as bisphosphonates suppress osteocyte apoptosis and may be localized within osteocyte lacunae. Bisphosphonates also reduce osteoclast viability and thereby hinder the repair of damaged tissue. Osteocyte lacunae contribute to toughening mechanisms. Following osteocyte apoptosis, the lacunar space undergoes mineralization, termed “micropetrosis”. Hypermineralized lacunae are believed to increase bone fragility. Using nanoanalytical electron microscopy with complementary spectroscopic and crystallographic experiments, postapoptotic mineralization of osteocyte lacunae in bisphosphonate-exposed human bone was investigated. We report an unprecedented presence of ∼80 nm to ∼3 μm wide, distinctly faceted, magnesium whitlockite [Ca18Mg2(HPO4)2(PO4)12] crystals and consequently altered local nanomechanical properties. These findings have broad implications on the role of therapeutic agents in driving biomineralization and shed new insights into a possible relationship between bisphosphonate exposure, availability of intracellular magnesium, and pathological calcification inside lacunae.

Keyword
Osteocyte lacuna, mineralization, micropetrosis, magnesium, whitlockite, bisphosphonates
National Category
Biomaterials Science Engineering and Technology
Research subject
Engineering Science with specialization in Materials Science
Identifiers
urn:nbn:se:uu:diva-330185 (URN)10.1021/acs.nanolett.7b02888 (DOI)000413057500048 ()28892393 (PubMedID)
Funder
Swedish Research Council, K2015-52X-09495-28-4)Region Västra Götaland
Available from: 2017-09-27 Created: 2017-09-27 Last updated: 2018-02-05Bibliographically approved
Barba, A., Diez-Escudero, A., Maazouz, Y., Rappe, K., Espanol, M., Montufar, E. B., . . . Ginebra, M.-P. (2017). Osteoinduction by Foamed and 3D-Printed Calcium Phosphate Scaffolds: Effect of Nanostructure and Pore Architecture. ACS Applied Materials and Interfaces, 9(48), 41722-41736.
Open this publication in new window or tab >>Osteoinduction by Foamed and 3D-Printed Calcium Phosphate Scaffolds: Effect of Nanostructure and Pore Architecture
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2017 (English)In: ACS Applied Materials and Interfaces, ISSN 1944-8244, E-ISSN 1944-8252, Vol. 9, no 48, p. 41722-41736Article in journal (Refereed) Published
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.

Keyword
osteoinduction, 3D-printing, foaming, nanostructure, calcium phosphate
National Category
Medical Materials
Research subject
Engineering Science with specialization in Materials Science
Identifiers
urn:nbn:se:uu:diva-335984 (URN)10.1021/acsami.7b14175 (DOI)000417669300011 ()
Funder
The Swedish Foundation for International Cooperation in Research and Higher Education (STINT), GA IG2011-2047
Available from: 2017-12-11 Created: 2017-12-11 Last updated: 2018-02-05Bibliographically approved
Organisations
Identifiers
ORCID iD: ORCID iD iconorcid.org/0000-0001-6663-6536

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