A dual function of copper in designing regenerative implants

Burghardt, Ines; Lüthen, Frank; Prinz, Cornelia; Kreikemeyer, Bernd; Zietz, Carmen; Neumann, Hava; Rychly, Joachim

doi:10.1016/j.biomaterials.2014.12.022

Cited by 193 publications

(143 citation statements)

References 39 publications

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“…The greater release of copper ions directly available to the cells when brought into contact with brushite particles, theoretically more soluble and resorbable than TCP, would have a directly proliferative effect on cells. The osteogenic effect of copper ions delivered either individually [43] or using CP cement [40], bioactive glass [44] or a titanium implant [45] as a carrier has been noticed earlier, but the precise mechanism remains unknown. A dose-dependent analysis of the effect of the material on two fundamentally different types of human cells – U87 glioblastoma cells and primary lung fibroblasts – demonstrated a proliferative effect exerted on the healthy cells and a reduction in viability of the malign U87 cells (Fig.…”

Section: Resultsmentioning

confidence: 99%

The Bone Building Blues: Self-hardening copper-doped calcium phosphate cement and its in vitro assessment against mammalian cells and bacteria

Rau

Graziani

et al. 2017

Materials Science and Engineering: C

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A blue calcium phosphate cement with optimal self-hardening properties was synthesized by doping whitlockite (β-TCP) with copper ions. The mechanism and the kinetics of the cement solidification process were studied using energy dispersive X-ray diffraction and it was found out that hardening was accompanied by the phase transition from TCP to brushite. Reduced lattice parameters in all crystallographic directions resulting from the rather low (1:180) substitution rate of copper for calcium was consistent with the higher ionic radius of the latter. The lower cationic hydration resulting from the partial Ca→Cu substitution facilitated the release of constitutive hydroxyls and lowered the energy of formation of TCP from the apatite precursor at elevated temperatures. Addition of copper thus effectively inhibited the formation of apatite as the secondary phase. The copper-doped cement exhibited an antibacterial effect, though exclusively against gram-negative bacteria, including E. coli, P. aeruginosa and S. enteritidis. This antibacterial effect was due to copper ions, as demonstrated by an almost negligible antibacterial effect of the pure, copper-free cement. Also, the antibacterial activity of the copper-containing cement was significantly higher than that of its precursor powder. Since there was no significant difference between the kinetics of the release of copper from the precursor TCP powder and from the final, brushite phase of the hardened cement, this has suggested that the antibacterial effect was not solely due to copper ions, but due to the synergy between cationic copper and a particular phase and aggregation state of calcium phosphate. Though inhibitory to bacteria, the copper-doped cement increased the viability of human glial E297 cells, murine osteoblastic K7M2 cells and especially human primary lung fibroblasts. That this effect was also due to copper ions was evidenced by the null effect on viability increase exhibited by the copper-free cements. The difference in the mechanism of protection of dehydratases in prokaryotes and eukaryotes was used as a rationale for explaining the hereby evidenced selectivity in biological response. It presents the basis for the consideration of copper as a dually effective ion when synergized with calcium phosphates: toxic for bacteria and beneficial for the healthy cells.

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Section: Resultsmentioning

confidence: 99%

The Bone Building Blues: Self-hardening copper-doped calcium phosphate cement and its in vitro assessment against mammalian cells and bacteria

Rau

Graziani

et al. 2017

Materials Science and Engineering: C

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“…As the dose of Cu 2+ was increased, the number of adhering bacteria (Figure 11c) was obviously reduced due to the contact-killing and release-killing mechanism, and the bacterial morphologies and membrane integrities were subject to serious disruption (Figure 11d). Results of biological compatibility experiments showed that the appropriate dose of Cu (0.67 wt %, Cu1) can improve the adhesion and proliferation of fibroblasts and significantly support denser collagen deposition, while excess Cu 2+ was poisonous to the cells (Figure 11e), will disrupt fundamental cellular processes and trigger apoptosis, just as mesenchymal stem cells [97]. Cu1 prepared in 0.00125 M Cu(CH 3 COO) 2 electrolyte with a Cu mass fraction of 0.67 delivered the best compromise between antibacterial effectiveness and cytotoxicity.…”

Section: Introduction Of Metallic Compounds Into Mao Electrolytementioning

confidence: 99%

Review of Antibacterial Activity of Titanium-Based Implants’ Surfaces Fabricated by Micro-Arc Oxidation

Zhang

Wang

et al. 2017

Coatings

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Ti and its alloys are the most commonly-used materials for biomedical applications. However, bacterial infection after implant placement is still one of the significant rising complications. Therefore, the application of the antimicrobial agents into implant surfaces to prevent implant-associated infection has attracted much attention. Scientific papers have shown that inorganic antibacterial metal elements (e.g., Ag, Cu, Zn) can be introduced into implant surfaces with the addition of metal nanoparticles or metallic compounds into an electrolyte via micro-arc oxidation (MAO) technology. In this review, the effects of the composition and concentration of electrolyte and process parameters (e.g., voltage, current density, oxidation time) on the morphological characteristics (e.g., surface morphology, bonding strength), antibacterial ability and biocompatibility of MAO antimicrobial coatings are discussed in detail. Anti-infection and osseointegration can be simultaneously accomplished with the selection of the proper antibacterial elements and operating parameters. Besides, MAO assisted by magnetron sputtering (MS) to endow Ti-based implant materials with superior antibacterial ability and biocompatibility is also discussed. Finally, the development trend of MAO technology in the future is forecasted.

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“…The SEM observation results in the present study showed that highconcentration alkali treatment could produce TNS not only on the titanium disc surface but also on the titanium screw surface, indicating that TNS implants may be easily manufactured by alkali solution immersion alone. Many surface modification methods have been shown to be effective for altering the surface characteristics and biological performance of titanium implant materials [15][16][17][18][19][20] . Nevertheless, these methods may be very complicated or require heavy surfacemodification machines, which are expensive and restrictive.…”

Section: Discussionmentioning

confidence: 99%

Evaluation of the Osteointegration of a Novel Alkali-Treated Implant System <i>In Vivo</i>

Kusumoto

Yin

Zhang

et al. 2017

J. Hard Tissue Biology.

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A dual function of copper in designing regenerative implants

Cited by 193 publications

References 39 publications

The Bone Building Blues: Self-hardening copper-doped calcium phosphate cement and its in vitro assessment against mammalian cells and bacteria

The Bone Building Blues: Self-hardening copper-doped calcium phosphate cement and its in vitro assessment against mammalian cells and bacteria

Review of Antibacterial Activity of Titanium-Based Implants’ Surfaces Fabricated by Micro-Arc Oxidation

Evaluation of the Osteointegration of a Novel Alkali-Treated Implant System <i>In Vivo</i>

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