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Effect of copper ion concentration on bacteria and cells
Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences. (Materials in Medicine)ORCID iD: 0000-0001-6057-7571
Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences. (Materials in Medicine)ORCID iD: 0000-0001-9529-650X
Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences. (Materials in Medicine)ORCID iD: 0000-0003-2709-9541
2019 (English)In: Materials, ISSN 1996-1944, E-ISSN 1996-1944, Vol. 12, no 22, article id 3798Article in journal (Refereed) Published
Abstract [en]

In the oral cavity, dental implants—most often made of commercially pure titanium—come in contact with bacteria, and antibacterial management has been researched extensively to improve patient care. With antibiotic resistance becoming increasingly prevalent, this has resulted in copper being investigated as an antibacterial element in alloys. In this study, the objective was to investigate the copper ion concentrations at which cyto-toxicity is avoided while bacterial inhibition is ensured, by comparing Cu ion effects on selected eukaryotes and prokaryotes. To determine relevant copper ion concentrations, ion release rates from copper and a 10 wt. % Cu Ti-alloy were investigated. Survival studies were performed on MC3T3 cells and Staphylococcus epidermidis bacteria, after exposure to Cu ions concentrations ranging from 9 × 10−3 to 9 × 10−12 g/mL. Cell survival increased from <10% to >90% after 24 h of exposure, by reducing Cu concentrations from 9 × 10−5 to 9 × 10−6 g/mL. Survival of bacteria also increased in the same range of Cu concentrations. The maximum bacteria growth was found at 9 × 10−7 g/mL, probably due to stress response. In conclusion, the minimum inhibitory concentrations of Cu ions for these prokaryotes and eukaryotes were found in the range from 9 × 10−5 to 9 × 10−6 g/mL. Interestingly, the Cu ion concentration correlating to the release rate of the 10 wt. % Cu alloy (9 × 10−8 g/mL) did not kill the bacteria, although this alloy has previously been found to be antibacterial. Further studies should investigate in depth the bacteria-killing mechanism of copper.

Place, publisher, year, edition, pages
Switzerland: MDPI, 2019. Vol. 12, no 22, article id 3798
Keywords [en]
Copper ion, Ion release, Antibacterial, S. Epidermidis, MC3T3
National Category
Other Materials Engineering
Identifiers
URN: urn:nbn:se:uu:diva-395279DOI: 10.3390/ma12223798ISI: 000502284400155PubMedID: 31752323OAI: oai:DiVA.org:uu-395279DiVA, id: diva2:1361672
Available from: 2019-10-16 Created: 2019-10-16 Last updated: 2020-01-14Bibliographically approved
In thesis
1. Development of titanium-copper alloys for dental applications
Open this publication in new window or tab >>Development of titanium-copper alloys for dental applications
2019 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Titanium alloys find wide application in the medical implants industry, which includes areas of orthopaedic and dental implants. The reason for the popularity of the material is high mechanical strength, low density, and reported growth of bone onto the material, as well as corrosion resistance. Despite the general success of titanium materials, a drawback is that it is vulnerable to bacterial colonization, which can cause implant failure through inflammatory diseases. Peri-implantitis is one such disease, which can lead to irreversible bone loss and subsequently implant instability.

This thesis focuses on the use of copper (Cu) as an antibacterial element in titanium alloys, where the purpose is designing inherently antibacterial materials.

With an understanding that copper can reduce bacterial populations by ion release of Cu into solutions, as well as by direct contact of bacteria with Cu surfaces: studies on the effect of Cu ions on bacteria and cells were conducted, in addition to studies on Ti-Cux alloys.

Varying Cu concentrations in solution were introduced to bacteria (Staphylococcus epidermidis) and cells (MC3T3 murine calvarial osteoblasts), and it was found that the lethal dosage for Cu ions was in the range from 9x10-5 to 9x10-6 g/ml, for bacteria and cells. The Cu ions were also found to cause a stress response for this bacteria at concentrations between 9x10-6 to 9x10-7 g/ml, and recommended to be avoided for implant materials.

For Ti-Cux binary alloys, studies established that a 10wt%Cu alloy, which released 9x10-8 g/ml, reduced the bacterial population by 27 % in 6 hours in a direct contact test. This alloy was found to be composed of intermetallic (Ti2Cu) and hexagonal closed packed titanium (HCP-Ti) crystals. A separate study on aged heat treated Ti-Cux alloys, showed that an additional phase of Ti3Cu was present in lower volume fraction. The aged alloys of Ti-Cux showed higher volume fraction of Ti2Cu but only a slightly higher antibacterial ability, compared to those without ageing. The hardness of the Ti-Cux alloys was however detrimentally affected by ageing, especially for the 10wt%Cu alloy.

Investigations on the alloying of Cu with an existing implant alloy, Ti-10wt%Ta-1.6wt%Nb-1.7wt%Zr (TNTZ), was also performed and at higher wt%Cu alloys with three-phased microstructures were present. Alloying of Cu in the TNTZ material increased hardness and with further development of this novel alloy, a potential biomaterial for clinical applications could be designed.

In conclusion, the results of this thesis demonstrate that the use of Cu in proximity to cells and bacteria requires dose dependent consideration for material design, so that antibacterial materials can be developed that do not harm tissue. The appropriate design of alloys can also be performed so as to allow antibacterial ability to be achieved, along with ensuring appropriate mechanical and corrosion properties. Furthermore, Cu as an antibacterial element can be alloyed into various titanium alloy systems and with further development in this area; antibacterial alloys could benefit the implant industry and patients alike.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2019. p. 65
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Science and Technology, ISSN 1651-6214 ; 1868
Keywords
Titanium, copper, antibacterial, Ti2Cu, biomaterials, Staphylococcus epidermidis, MC3T3 cells
National Category
Medical Materials
Identifiers
urn:nbn:se:uu:diva-395303 (URN)978-91-513-0782-4 (ISBN)
Public defence
2019-12-13, Häggsalen, Ångströmlaboratoriet, Lägerhyddsvägen 1, Uppsala, 13:15 (English)
Opponent
Supervisors
Available from: 2019-11-18 Created: 2019-10-17 Last updated: 2019-11-18

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