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SIMS21, Poland 2017 - Håkan Nygren abstract

Håkan Nygren oral presentation (OB4-Fri1-1-4)

Metal oxides, hydroxyapatite, bone healing and remodeling

Håkan Nygren1, Per Malmberg2

1 Dept of Medical Chemistry and Cell Biology - University of Gothenburg, POB 440, 405 30 Göteborg, Sweden
2 Dept of Chemistry and Chemical Engineering - Chalmers University of Technology, Kemigården, 412 96 Göteborg, Sweden


Magnesium has been suggested [1, 2] for application as biodegradable implants, but there is still a lack of understanding of the role of its corrosion products and their influence on the tissue response at the implantation site. The approach in this study is to implant MgO in rat tibia and follow the healing process during 1-3 weeks of healing comparing the results to those of sham-operated controls. In a second set of experiments, we used other metal oxides that have been reported to stimulate bone formation, MnO and ZnO. The MnO and ZnO where more efficient than MgO in catalyzing the formation of hydroxyapatite, and were also more efficient in promoting bone healing in vivo.

The healing bone was analysed by histology, imaging mass spectrometry (ToF-SIMS) and SEM equipped with an EDX-analyser, as described previously [3, 4]. Metal oxides incubated in vitro in cell culture medium were analyzed by XPS and ToF-SIMS.

The normal healing process, callus bone after 1 week of healing, remodeling and completed healing after 3 weeks was little affected by MgO implantation when examined by histology. However, the EDX-analysis showed a high content of mineral in the bone marrow after 1 week of healing with implanted MgO and a higher Ca content in the cortical bone.

In-vitro studies of MgO incubated in tissue culture medium confirmed that MgO catalyses the formation of calcium phosphates. The Ca/P ratio of the mineral formed was lower than expected for hydroxyapatite (HA) as shown by XPS, but ToF-SIMS analysis showed also a content of HA. Experiments, using MnO and ZnO implants showed that MnO and ZnO where more efficient than MgO in catalyzing the formation of hydroxyapatite, and were also more efficient in promoting bone healing in vivo.

The catalysis of HA-formation by metal oxides and the production of HA by cells has been shown previously [5, 6]. The generalization of the phenomenon to ZnO and MnO is a novel finding. The catalysis of HA by metal oxides is also seen with TiO2 in contact with tissue fluid [4]. The healing of TiO2 in vivo was analysed by depth profiling Tof-SIMS, showing the HA on TiO2 in situ.

REFERENCES: 1 F. Witte. (2010) Acta Biomater. 6:1680-92. 2 F. Witte, Hort N, Vogt C, Cohen S, Kainer KU, Willumeit R, Feyerabend F. (2008). Current Opinion in Solid State and Material Science. 12:63-72. 3H. Nygren, Chaudhry M, Gustafsson S, Kjeller G, Malmberg P, Johansson KE. (2014) Journal of functional biomaterials. 5:158-66. 4 H. Nygren, Ilver L, Malmberg P. (2016) Journal of functional biomaterials.7: 7-12. 5 V. Wagener, Virtanen S. (2016) Materials science & engineering C, Materials for biological applications. 63:341-51.

6 N.A. Agha, Feyerabend F, Mihailova B, Heidrich S, Bismayer U, Willumeit-Romer R. (2016) Materials science & engineering C, Materials for biological applications. 58:817-25.