In vivo response to a low-modulus PMMA bone cement in an ovine model.

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 vivo biocompatibility 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. STATEMENT OF SIGNIFICANCE: The benefits of using linoleic acid to reduce the stiffness of poly(methyl methacrylate) bone cement has been demonstrated previously, with the in vitro and in vivo response of the modified cement in small animals reported as comparable to the base cement. However, biocompatibility evaluation of modified cement in large animal models for future clinical use has yet to be performed. In this study, modified and unmodified cements were injected into bone defects created in sheep. We showed that the inflammatory response of the modified cement was similar to the base cement, allowing remodelling of the bone surrounding the implant. This demonstrates the potential of low-modulus PMMA cement in the field of bone augmentation.