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In this study, we propose a new approach to generate bioactive PMMA surfaces directly at the site of implantation by adding the amphiphilic molecule phosphorylated 2\u2010hydroxyethylmethacrylate (HEMA\u2010P) to commercial PMMA bone cement, both with or without addition of 1\u20135% soluble calcium and carbonate salts. The setting behavior as well as the mechanical properties, the bonding quality at the metal\/cement interface, mineral deposition, and cellular response for different cement modifications were investigated <jats:italic>in vitro<\/jats:italic>. The addition of HEMA\u2010P resulted in entirely positive effects with respect to proliferation and differentiation of osteoblast\u2010like cells (SaOs\u20102) and a very tight contact at the metal\/cement interface. No detrimental changes of other properties were detected. The additional incorporation of salts provoked an increased deposition of calcium phosphate minerals but no further improvement in SaOs\u20102 cell differentiation. A significant decrease in polarization resistance for cements with high salt content (5%) was attributed to debonding between metal and cement. The results suggest an improved clinical performance of PMMA\/HEMA\u2010P composites, which might be further enhanced by small amounts of the soluble salts. \u00a9 2012 Wiley Periodicals, Inc. 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