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Simvastatin and zinc synergistically enhance osteoblasts activity and decrease the acute response of inflammatory cells

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Abstract

Several ceramic biomaterials have been suggested as promising alternatives to autologous bone to replace or restore bone after trauma or disease. The osteoinductive potential of most scaffolds is often rather low by themselves and for this reason growth factors or drugs have been supplemented to these synthetic materials. Although some growth factors show good osteoinductive potential their drawback is their high cost and potential severe side effects. In this work the combination of the well-known drug simvastatin (SVA) and the inorganic element Zinc (Zn) is suggested as a potential additive to bone grafts in order to increase their bone regeneration/formation. MC3T3-E1 cells were cultured with Zn (10 and 25 µM) and SVA (0.25 and 0.4 µM) for 10 days to evaluate proliferation and differentiation, and for 22 days to evaluate secretion of calcium deposits. The combination of Zn (10 µM) and SVA (0.25 µM) significantly enhanced cell differentiation and mineralization in a synergetic manner. In addition, the release of reactive oxygen species (ROS) from primary human monocytes in contact with the same concentrations of Zn and SVA was evaluated by chemiluminescence. The combination of the additives decreased the release of ROS, although Zn and SVA separately caused opposite effects. This work shows that a new combination of additives can be used to increase the osteoinductive capacity of porous bioceramics.

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Acknowledgments

This work was co-funded by Marie Curie Actions FP7-PEOPLE-2011-COFUND (GROWTH 291795) via the VINNOVA programme Mobility for Growth (project n. 2013-01260) and Lars Hiertas Minne Foundation (project n. FO2014-0334). Financial support from Uppsala University is acknowledged by MT, HE and MM.

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Authors and Affiliations

  1. Department Engineering Sciences, Uppsala University, Uppsala, Sweden

    Maryam Montazerolghaem, Yi Ning, Håkan Engqvist, Marjam Karlsson Ott, Maria Tenje & Gemma Mestres

  2. Science for Life Laboratory, Uppsala, Sweden

    Marjam Karlsson Ott & Maria Tenje

  3. Department Biomedical Engineering, Lund University, Lund, Sweden

    Maria Tenje

Authors
  1. Maryam Montazerolghaem
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  2. Yi Ning
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  3. Håkan Engqvist
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  6. Gemma Mestres
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Correspondence to Gemma Mestres.

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Montazerolghaem, M., Ning, Y., Engqvist, H. et al. Simvastatin and zinc synergistically enhance osteoblasts activity and decrease the acute response of inflammatory cells. J Mater Sci: Mater Med 27, 23 (2016). https://doi.org/10.1007/s10856-015-5639-4

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  • DOI: https://doi.org/10.1007/s10856-015-5639-4

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