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Calcium phosphate cements with strontium halides as radiopacifiers
Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences. (Materials in Medicine)
Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences. (Materials in Medicine)
Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences. (Materials in Medicine)
Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences. (Materials in Medicine)
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2014 (English)In: Journal of Biomedical Materials Research. Part B - Applied biomaterials, ISSN 1552-4973, E-ISSN 1552-4981, Vol. 102, no 2, 250-259 p.Article in journal (Refereed) Published
Abstract [en]

High radiopacity is required to monitor the delivery and positioning of injectable implants. Inorganic nonsoluble radiopacifiers are typically used in nondegradable bone cements; however, their usefulness in resorbable cements is limited due to their low solubility. Strontium halides, except strontium fluoride, are ionic water-soluble compounds that possess potential as radiopacifiers. In this study, we compare the radiopacity, mechanical properties, composition, and cytotoxicity of radiopaque brushite cements prepared with strontium fluoride (SrF2), strontium chloride (SrCl2·6H2O), strontium bromide (SrBr2), or strontium iodide (SrI2). Brushite cements containing 10 wt % SrCl2·6H2O, SrBr2, or SrI2 exhibited equal to or higher radiopacity than commercial radiopaque cements. Furthermore, the brushite crystal lattice in cements that contained the ionic radiopacifiers was larger than in unmodified cements and in cements that contained SrF2, indicating strontium substitution. Despite the fact that the strontium halides increased the solubility of the cements and affected their mechanical properties, calcium phosphate cements containing SrCl2·6H2O, SrBr2, and SrI2 showed no significant differences in Saos-2 cell viability and proliferation with respect to the control. Strontium halides: SrCl2·6H2O, SrBr2, and SrI2 may be potential candidates as radiopacifiers in resorbable biomaterials although their in vivo biocompatibility, when incorporated into injectable implants, is yet to be assessed.

Place, publisher, year, edition, pages
2014. Vol. 102, no 2, 250-259 p.
Keyword [en]
water-soluble radiopacifier, strontium halide, brushite, radiopaque bone cement, calcium phosphate
National Category
Biomaterials Science Engineering and Technology
Research subject
Engineering Science with specialization in Materials Science
Identifiers
URN: urn:nbn:se:uu:diva-211052DOI: 10.1002/jbm.b.33002ISI: 000330639400007OAI: oai:DiVA.org:uu-211052DiVA: diva2:665171
Funder
VinnovaSwedish Research CouncilCarl Tryggers foundation
Available from: 2013-11-19 Created: 2013-11-19 Last updated: 2017-12-06
In thesis
1. Injectable Biomaterials for Spinal Applications
Open this publication in new window or tab >>Injectable Biomaterials for Spinal Applications
2014 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

The use of injectable biomaterials is growing as the demands for minimally invasive procedures, and more easily applicable implants become higher, but their availability is still limited due to the difficulties associated to their design.

Each year, more than 700,000 vertebral compression fractures (VCF’s) are reported in the US and 500,000 VCF’s in Europe due to primary osteoporosis only. VCF’s can compromise the delicacy of the spinal canal and also cause back pain, which affects the patient’s quality of life. Vertebroplasty was developed in the 80’s, and has proven to be a safe minimally invasive procedure that can, quickly and sustainably, relieve the pain in patients experiencing VCF’s. However, biomaterials for vertebroplasty still have limitations. For instance, ceramic bone cements are difficult to distinguish from the bone using X-ray techniques. On the other hand, acrylic bone cements may cause adjacent vertebral fractures (AVF’s). Large clinical studies have indicated that 12 to 20% vertebroplasty recipients developed subsequent vertebral fractures, and that 41 to 67% of these, were AVF’s. This may be attributed to the load shifting and increased pressure on the adjacent endplates reached after vertebroplasty with stiff cements.

The primary aim of this thesis was to develop better injectable biomaterials for spinal applications, particularly, bone cements for vertebroplasty. Water-soluble radiopacifiers were first investigated to enhance the radiopacity of resorbable ceramic cements. Additionally, different strategies to produce materials that mechanically comply with the surrounding tissues (low-modulus bone cements) were investigated. When a suitable low-modulus cement was produced, its performance was evaluated in both bovine bone, and human vertebra ex vivo models.

In summary, strontium halides showed potential as water-soluble radiocontrast agents and could be used in resorbable calcium phosphates and other types of resorbable biomaterials. Conversely, linoleic acid-modified (low-modulus) cements appeared to be a promising alternative to currently available high-modulus cements. It was also shown that the influence of the cement properties on the strength and stiffness of a single vertebra depend upon the initial bone volume fraction, and that at low bone volume fractions, the initial mechanical properties of the vertebroplasty cement become more relevant. Finally, it was shown that vertebroplasty with low-modulus cements is biomechanically safe, and could become a recommended minimally invasive therapy in selected cases, especially for patients suffering from vertebral compression fractures due to osteoporosis.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2014. 66 p.
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Science and Technology, ISSN 1651-6214 ; 1114
Keyword
injectable, biomaterials, bone cement, vertebral compression fractures, spine, radiopacity, minimally invasive treatment, low-modulus cement, oligomer, PMMA, calcium phosphate, vertebroplasty, bone
National Category
Biomaterials Science
Research subject
Engineering Science with specialization in Materials Science
Identifiers
urn:nbn:se:uu:diva-215606 (URN)978-91-554-8854-3 (ISBN)
Public defence
2014-02-28, Polhemssalen, Ångströmlaboratoriet, Lägerhyddsvägen 1, Uppsala, 13:00 (English)
Opponent
Supervisors
Available from: 2014-02-05 Created: 2014-01-15 Last updated: 2014-02-10
2. Additives Increasing the Bone-Forming Potential around Calcium Phosphate Cements: Statin, Strontium and Silicon
Open this publication in new window or tab >>Additives Increasing the Bone-Forming Potential around Calcium Phosphate Cements: Statin, Strontium and Silicon
2015 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

More than one million people worldwide receive some kind of bone graft each year. Grafts are often needed following bone tumour removal or traumatic fractures to fill voids in the bone and to aid in the healing process. The most common method involves bone transplantation, in which bone tissue is taken from one site to fill the defect in another site. The procedure thus involves two surgeries, which leads to an increased risk of complications. New, synthetic graft materials that can be used to fill defects and minimise the complications associated with bone tissue harvesting are therefore necessary. The synthetic materials available today lack the inherent biological factors of bone that stimulate the bone regeneration process. Much of today’s research concerning synthetic bone graft materials aims to solve this issue and researchers have suggested several different strategies.

The purpose of this thesis is to improve the performance of acidic calcium phosphate cements, which are materials used as synthetic bone grafts. By combining these cements with drugs or ion additives, local delivery could be achieved with the potential to stimulate bone formation. Two different combinations were attempted in this thesis: cement in combination with simvastatin, or cement in combination with strontium halide salts. Both simvastatin and strontium are known to positively affect bone formation. The efficacy of the cements with the additives was evaluated using different bone cell cultures. The results regarding simvastatin showed that the cement’s mechanical property was not affected upon drug loading, and that the drug was released by a diffusion-controlled mechanism. Moreover, results showed that simvastatin stimulated the bone-forming cells (osteoblasts) to produce more bone tissue, while it inhibited bone-degrading cells (osteoclasts) from degrading the cement. These findings suggest that simvastatin could aid in the bone regeneration process in the local area surrounding the cement.

The main purpose of the study using strontium halide salts was to increase the cement’s X-ray contrast, which is a property used to monitor cement during injection. In addition, strontium is believed to positively affect bone cells. The X-ray contrast did increase after the addition of 10 wt% strontium bromide or strontium iodide, while the cell study results did not indicate any significant effects on the bone-forming cells.

In the last section of this thesis, zebrafish were used as a model to evaluate bone formation upon treatment with degradation products from synthetic bone grafts. The zebrafish is a small organism with 70 % gene homology to humans; due to its transparency, fast development and ease of handling, it is an interesting model for high-throughput studies. Silicate, which is an ionic degradation product of many different bone substitute materials, was used as a proof-of-concept to visualise bone formation in these fish. The results showed an increased bone formation upon treatment with 0.625 μM silicate ions. The results suggest that this model could be used as a complement to bone cell culture studies in pre-clinical evaluations of the degradation products of bone substitute materials, thus helping researchers to design materials with degradation products that could stimulate bone formation.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2015. 69 p.
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Science and Technology, ISSN 1651-6214 ; 1232
Keyword
Calcium Phosphate Cements, Osteoblast, Osteoclast, Monetite, Zebrafish, Simvastatin, Strontium, Silicon
National Category
Medical Materials
Research subject
Engineering Science with specialization in Materials Science
Identifiers
urn:nbn:se:uu:diva-246289 (URN)978-91-554-9183-3 (ISBN)
Public defence
2015-04-22, Häggsalen, Ångströmlaboratoriet, Uppsala, 13:00 (English)
Opponent
Supervisors
Available from: 2015-03-31 Created: 2015-03-04 Last updated: 2015-04-17

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López, AlejandroMontazerolghaem, MaryamEngqvist, HåkanOtt, Marjam KarlssonPersson, Cecilia

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