A dual function of copper in designing regenerative implants

Abstract The supply of titanium implants which are widely used in orthopaedics with both regenerative and anti-microbial properties will achieve a great progress in bone regeneration. We asked, whether by appropriate concentrations of copper ions it will be possible both to inhibit growth of bacteri...

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Published in:	Biomaterials Vol. 44; pp. 36 - 44
Main Authors:	Burghardt, Ines, Lüthen, Frank, Prinz, Cornelia, Kreikemeyer, Bernd, Zietz, Carmen, Neumann, Hans-Georg, Rychly, Joachim
Format:	Journal Article
Language:	English
Published:	Netherlands Elsevier Ltd 01-03-2015
Subjects:	Advanced Basic Science Anti-Infective Agents - pharmacology Antimicrobial ANTISEPTICS Bacteria Biocompatibility Biological Biomarkers - metabolism Biomedical materials Bones Calcium - metabolism Cell Death - drug effects Cell Differentiation - drug effects Cell Movement - drug effects Cell Proliferation - drug effects Copper Copper - pharmacology COPPER IONS Dentistry Humans Mesenchymal stem cell Osteogenesis - drug effects Prostheses and Implants Prosthesis Design Regenerative Regenerative Medicine Staphylococcus aureus Staphylococcus aureus - drug effects Staphylococcus aureus - growth & development Surface Properties Surgical implants Titanium Titanium - pharmacology Antimicrobial Mesenchymal stem cell Titanium Bacteria Copper
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Summary:	Abstract The supply of titanium implants which are widely used in orthopaedics with both regenerative and anti-microbial properties will achieve a great progress in bone regeneration. We asked, whether by appropriate concentrations of copper ions it will be possible both to inhibit growth of bacteria and stimulate biological responses in mesenchymal stem cells (MSC). Using titanium material which released galvanically deposited copper at concentrations from 0.3 to 1.75 mM, growth of planktonic Staphylococcus aureus was blocked and more importantly adherent bacteria were cleared from the material surface within 24 h. To test biological responses of human bone marrow derived MSC due to copper ions, we found that copper stimulated the proliferation of MSC in a narrow concentration range around 0.1 mM. Similar copper concentrations enhanced osteogenic differentiation of MSC when cells were cultured in osteogenic differentiation medium. We observed increased activity of alkaline phosphatase (ALP), higher expression of collagen I, osteoprotegerin, osteopontin and finally mineralization of the cells. We conclude that titanium implants that release copper ions can be effective against bacterial infections at higher concentrations of copper near the implant surface and can promote bone regeneration when its concentration becomes lower due to diffusion.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	0142-9612 1878-5905
DOI:	10.1016/j.biomaterials.2014.12.022