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Bone-compliant cements for vertebral augmentation
Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.ORCID iD: 0000-0003-4139-6913
2018 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Acrylic bone cement based on poly(methyl methacrylate) (PMMA) is commonly used during vertebral augmentation procedures for the treatment of osteoporosis-induced vertebral compression fractures. However, the high stiffness of the cement compared to that of the surrounding trabecular bone is presumed to facilitate the formation of new fractures shortly after surgery. The aim of the thesis was to develop and evaluate a PMMA-based bone cement that better matches the mechanical properties of vertebral trabecular bone. To fulfill this objective, different compounds were added to the initial formulation of bone cement to modify its functional properties. Linoleic acid (LA) was found to give the best combination of strength and stiffness without negative effects on the handling properties and its use was therefore further investigated. In particular, different application-specific mechanical properties of LA-modified cement as well as itsin vivoperformance in an ovine model were assessed. 

In summary, LA-modified cement exhibited bone-compliant mechanical properties immediately after incorporation of the additive, as well as adequate handling properties, in particular a lower polymerization temperature and appropriate setting time. The screw pullout strength from low-modulus cement was substantially reduced compared to regular PMMA cement, but comparable to some calcium phosphate based cements. The fatigue limit of LA-modified cement was considerably lower compared to regular PMMA bone cement when tested in physiological solution, but still higher than stresses measured in the spine during daily activities. The modified cement displayed similar inflammatory response in vivoto conventional cement, with no evidence of additional cytotoxicity due to the presence of LA. Finally, it was possible to sterilize the additive without significantly compromising its function in the PMMA cement.

The results from this thesis support further evaluation of the material towards the intended clinical application. 

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2018. , p. 92
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Science and Technology, ISSN 1651-6214 ; 1676
Keywords [en]
bone cement, low modulus, vertebroplasty
National Category
Materials Engineering
Research subject
Engineering Science with specialization in Materials Science
Identifiers
URN: urn:nbn:se:uu:diva-349028ISBN: 978-91-513-0351-2 (print)OAI: oai:DiVA.org:uu-349028DiVA, id: diva2:1199312
Public defence
2018-06-07, Häggsalen, Ångströmlaboratoriet, Lägerhyddsvägen 1, Uppsala, 09:00 (English)
Opponent
Supervisors
Available from: 2018-05-16 Created: 2018-04-20 Last updated: 2018-10-08
List of papers
1. The effect of unsaturated fatty acid and triglyceride oil addition on the mechanical and antibacterial properties of acrylic bone cements
Open this publication in new window or tab >>The effect of unsaturated fatty acid and triglyceride oil addition on the mechanical and antibacterial properties of acrylic bone cements
Show others...
2015 (English)In: Journal of biomaterials applications, ISSN 0885-3282, E-ISSN 1530-8022, Vol. 30, no 3, p. 279-289Article in journal (Refereed) Published
National Category
Textile, Rubber and Polymeric Materials Other Materials Engineering
Research subject
Engineering Science with specialization in Materials Science
Identifiers
urn:nbn:se:uu:diva-251353 (URN)10.1177/0885328215581316 (DOI)000361767300003 ()
Funder
EU, FP7, Seventh Framework Programme, FP7-PEOPLE-2010-268134VINNOVA, 2010-02073The Swedish Foundation for International Cooperation in Research and Higher Education (STINT), IG2011-2047
Available from: 2015-04-16 Created: 2015-04-16 Last updated: 2018-04-20Bibliographically approved
2. In vivo response to a low-modulus PMMA bone cement in an ovine model
Open this publication in new window or tab >>In vivo response to a low-modulus PMMA bone cement in an ovine model
2018 (English)In: Acta Biomaterialia, ISSN 1742-7061, E-ISSN 1878-7568, Vol. 72, p. 362-370Article in journal (Refereed) Published
Abstract [en]

Poly(methyl methacrylate) (PMMA) is the most commonly used material for the treatment of osteoporosis-induced vertebral compression fractures. However, its high stiffness may introduce an increased risk of adjacent vertebral fractures post-surgery. One alternative in overcoming this concern is the use of additives. This presents its own challenge in maintaining an adequate biocompatibility when modifying the base cement. The aim of this study was to evaluate the in vivobiocompatibility of linoleic acid (LA)-modified acrylic bone cement using a large animal model for the first time, in order to further advance towards clinical use. A worst-case approach was used, choosing a slow-setting base cement. The in vitro monomer release from the cements was also assessed. Additional material characterization, including mechanical tests, are summarized in Appendix A. Unmodified and LA-modified cements were injected into a total of 56 bone defects created in the femur and humerus of sheep. Histopathologic and histomorphometric analysis indicated that LA-modified cement showed a harmless tissue response similar to that of the unmodified cement. Adjacent bone remodeling was observed microscopically 4 weeks after implantation, suggesting a normal healing process of the bone tissues surrounding the implant. LA-modified cement exhibited lower mechanical properties, with a reduction in the elastic modulus of up to 65%. The handling properties were slightly modified without negatively affecting the injectability of the base cement. LA-modified bone cement showed good biocompatibility as well as bone compliant mechanical properties and may therefore be a promising material for the treatment of osteoporotic vertebral fractures. 

Place, publisher, year, edition, pages
Elsevier, 2018
Keywords
Poly (methyl methacrylate), bone cement, low-modulus, In vivo, linoleic acid
National Category
Other Materials Engineering Medical Materials Biomaterials Science
Research subject
Engineering Science with specialization in Materials Science
Identifiers
urn:nbn:se:uu:diva-349033 (URN)10.1016/j.actbio.2018.03.014 (DOI)000432766900031 ()29559365 (PubMedID)
Funder
VINNOVA, 2010-02073
Available from: 2018-04-20 Created: 2018-04-20 Last updated: 2018-12-05
3. Functional properties of low-modulus PMMA bone cements containing linoleic acid
Open this publication in new window or tab >>Functional properties of low-modulus PMMA bone cements containing linoleic acid
(English)In: Article in journal (Other (popular science, discussion, etc.)) In press
Abstract [en]

Spinal augmentation using rigid acrylic bone cement may facilitate the formation of additional vertebral compression fractures (VCFs) in the vicinity of the collapsed vertebrae. It has been hypothesized that the use of less stiff bone cement could reduce the occurrence of adjacent VCFs. Acrylic bone cement modified with linoleic acid (LA) has been reported as a promising low-modulus alternative. However, several key properties remain unexplored. In this study, the flexural properties and screw augmentation capacity of the LA-modified cement were evaluated. The effect of sterilization through autoclaving was assessed in terms of LA composition and cement handling properties, glass transition temperature (Tg) and quasi-static compressive mechanical properties. 

The bending modulus, bending strength and pull-out force were, as with the compressive properties, significantly affected by the addition of LA, giving mechanical properties closer to those of vertebral trabecular bone. The maximum polymerization temperature was significantly lower for LA-modified cement (28.2 ± 0.4 °C for non-sterile and 31.1 ± 1.1 °C for sterile material) than the control cement (66.8 ± 3 °C). The setting time of the cements remained comparable, at between 20-25 minutes, but LA-modified cements could be injected over a longer period than the regular cement. Sterilized and non-sterilized LA-modified cements displayed similar injectability and mechanical properties over time. The Tgof sterilized LA-cement (78.0 ± 3.2 °C) was not statistically different from the Tgof non-sterilized LA-cement (74.7 ± 4.8 °C) but both were significantly lower than the Tgof the control cement (102.8 ± 1.3 °C). 

In summary, a sterilization process could be used without significantly affecting the functional properties of LA-modified cement. These cements displayed excellent handling and mechanical properties that more closely match those of osteoporotic vertebral bone. They exhibited a pullout strength comparable to some ceramic bone cements, demonstrating potential for use in applications where hardware needs to be applied. 

Keywords
Acrylic bone cement, low-modulus, mechanical properties, bending, vertebroplasty, screw, pullout, sterilization
National Category
Materials Engineering
Research subject
Engineering Science with specialization in Materials Science
Identifiers
urn:nbn:se:uu:diva-349057 (URN)
Available from: 2018-04-20 Created: 2018-04-20 Last updated: 2018-04-20
4. Compressive fatigue properties of commercially available standard and low-modulus acrylic bone cements intended for vertebroplasty
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 Biomaterials Science Medical Materials
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: 2018-12-05
5. Long-term mechanical properties of a low-modulus bone cement for the treatment of vertebral compression fractures
Open this publication in new window or tab >>Long-term mechanical properties of a low-modulus bone cement for the treatment of vertebral compression fractures
(English)In: Article in journal (Other (popular science, discussion, etc.)) In press
Keywords
Acrylic bone cement, low-modulus, elastic modulus, compression, fatigue, vertebroplasty
National Category
Materials Engineering
Research subject
Engineering Science with specialization in Materials Science
Identifiers
urn:nbn:se:uu:diva-349059 (URN)
Available from: 2018-04-20 Created: 2018-04-20 Last updated: 2018-04-20

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