title: 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 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.
authors.affiliation: Laboratory of Cell Biology, Rostock University Medical Center, Schillingallee 69, 18057 Rostock, Germany.
authors.forename: Ines
authors.initials: I
authors.lastname: Burghardt
authors.affiliation: Laboratory of Cell Biology, Rostock University Medical Center, Schillingallee 69, 18057 Rostock, Germany.
authors.forename: Frank
authors.initials: F
authors.lastname: Lüthen
authors.affiliation: DOT GmbH, 18059 Rostock, Germany.
authors.forename: Cornelia
authors.initials: C
authors.lastname: Prinz
authors.affiliation: Institute of Medical Microbiology, Virology and Hygiene, Rostock University Medical Center, 18057 Rostock, Germany.
authors.forename: Bernd
authors.initials: B
authors.lastname: Kreikemeyer
authors.affiliation: Department of Orthopaedics, Biomechanics and Implant Technology Research Laboratory, Rostock University Medical Center, 18057 Rostock, Germany.
authors.forename: Carmen
authors.initials: C
authors.lastname: Zietz
authors.affiliation: DOT GmbH, 18059 Rostock, Germany.
authors.forename: Hans-Georg
authors.initials: HG
authors.lastname: Neumann
authors.affiliation: Laboratory of Cell Biology, Rostock University Medical Center, Schillingallee 69, 18057 Rostock, Germany. Electronic address: joachim.rychly@med.uni-rostock.de.
authors.forename: Joachim
authors.initials: J
authors.lastname: Rychly
mesh_terms: D000890:Anti-Infective Agents / Q000494:pharmacology; D015415:Biomarkers / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D016923:Cell Death / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D003300:Copper / Q000494:pharmacology*; D006801:Humans; D010012:Osteogenesis / Q000187:drug effects; D019736:Prostheses and Implants; D011474:Prosthesis Design; D044968:Regenerative Medicine; D013211:Staphylococcus aureus / Q000187:drug effects / Q000254:growth & development; D013499:Surface Properties; D014025:Titanium / Q000494:pharmacology
chemical_list: D000890:Anti-Infective Agents; D015415:Biomarkers; D003300:Copper; D014025:Titanium; D002118:Calcium
keywords: Antimicrobial; Bacteria; Copper; Mesenchymal stem cell; Titanium