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In vivo response to a low-modulus PMMA bone cement in an ovine model
Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences. (Materials in Medicine)ORCID iD: 0000-0003-4139-6913
Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences. (Materials in Medicine)
Inossia AB, Stockholm, Sweden.
Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences. (Materials in Medicine)ORCID iD: 0000-0001-6663-6536
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. Vol. 72, p. 362-370
Keywords [en]
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: urn:nbn:se:uu:diva-349033DOI: 10.1016/j.actbio.2018.03.014ISI: 000432766900031PubMedID: 29559365OAI: oai:DiVA.org:uu-349033DiVA, id: diva2:1199274
Funder
VINNOVA, 2010-02073Available from: 2018-04-20 Created: 2018-04-20 Last updated: 2018-12-05
In thesis
1. Bone-compliant cements for vertebral augmentation
Open this publication in new window or tab >>Bone-compliant cements for vertebral augmentation
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
bone cement, low modulus, vertebroplasty
National Category
Materials Engineering
Research subject
Engineering Science with specialization in Materials Science
Identifiers
urn:nbn:se:uu:diva-349028 (URN)978-91-513-0351-2 (ISBN)
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

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Robo, CélineHulsart Billström, GryPersson, Cecilia

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