Postoperative implant-associated infection is still an unresolved and serious complication in modern surgery. Antibacterial and biocompatible surfaces could both reduce infection rates and promote tissue integration. In this respect, a comparative study of the antibacterial as well as the biocompatible potential of different metal ions in vitro is presented. The assays used were growth inhibition tests with different metal salts carried out with tissue cells and bacteria under corresponding culture conditions. Additionally, in vitro tests in direct surface contact with tissue cells and bacteria onto a novel copper containing sol-gel derived titanium dioxide coating (Cu-TiO2) and a fourfold Cu-TiO2 coating were performed. The values were compared to a non-filled titanium dioxide coating and standard Ti6Al4V alloy. SEM-investigations were performed to approve the results of the in vitro tests. Among Ag+, Zn2+, Co2+, Al3+ and Hg2+, the growth inhibition tests revealed an outstanding position of copper ions as antibacterial but nevertheless bio-tolerant additive. These results were affirmed by the cell tests in direct surface contact and SEM-investigations, where best cell growth was found on the Cu-TiO2 coatings. Highest antibacterial properties with a tolerable cytocompatibility could be observed on the fourfold Cu-TiO2 coatings. Consequently, surfaces with custom-tailored antibacterial properties may be established and could be of particular interest in revision and tumor arthroplasty.
Implant infections remain feared and severe complications after total joint arthroplasty. The incidence of multi-resistant pathogens, causing such infections, is rising continuously, and orthopaedic surgeons are confronted with an ever-changing resistance pattern. Anti-infectious surface coatings aim for a high local effective concentration and a low systemic toxicity at the same time. Antibacterial efficacy and biomechanical stability of a novel broad-spectrum anti-infectious coating is assessed in the present study. Antibacterial efficacy of a sol-gel derived titanium dioxide (TiO(2)) coating for metal implants with and without integrated copper ions as antibiotic agent was assessed against methicillin resistant Staphylococcus aureus (MRSA 27065). Both bacterial surface adhesion and growth of planktonic bacteria were assessed with bare and various TiO(2)-coated Ti6Al4V metal discs. Furthermore, bonding strength of the TiO(2) surface coating, using standard testing procedures, as well as surface roughness were determined. We found a significant reduction of the bacterial growth rate for the coatings with integrated copper ions, with highest reduction rates observed for a fourfold copper TiO(2)-coating. Pure TiO(2) without integrated copper ions did not reduce bacterial growth compared to uncoated Ti6Al4V. The coating was not detached from the substrate by standard adhesive failure testing, which indicated an excellent durability of the implant coating. The TiO(2) coating with integrated copper ions could offer a new strategy for preventing implant-associated infections, with antibacterial properties not only against the most common bacteria causing implant infections but also against multiresistant strains such as MRSA.
The purpose of our study was to investigate the antibacterial effect of a spacer (Ti6Al4V) coated with 4x Cu-TiO2 in an animal model simulating an acute periprosthetic infection by Staphylococcus aureus. Ti6Al4 bolts contaminated with Staphylococcus aureus were implanted into the femoral condyle of rabbits (n = 36) divided into 3 groups. After one week in group 1 (control) the bolts were removed without any replacement. In group2 Ti6Al4V bolts with a 4x Cu-TiO2 coating and in group 3 beads of a gentamicin-PMMA chain were imbedded into the borehole. Microbiological investigation was performed at the primary surgery, at the revision surgery and after scarification of the rabbits 3 weeks after the first surgery. Blood tests were conducted weekly. The initial overall infection rate was 88.9%. In group 2 and 3 a significant decrease of the infection rate was shown in contrast to the control group. The C-reactive protein (CRP) levels declined one week after the first surgery except in the control group where the CRP level even increased. This is the first in vivo study that demonstrated the antibacterial effects of a fourfold Cu-TiO2 coating. For the future, the coating investigated could be a promising option in the treatment of implant-associated infections.
The aim of this study was the investigation of a copper-filled TiO2 coating, that in vitro showed good antibacterial properties combined with good tissue tolerance in an animal model. To better understand the antibacterial mechanism of the bioactive coating the release of copper (Cu) ions over time was monitored to be able to detect possible threats as well as possible fields of application. 30 New Zealand White rabbits were divided into two groups with 15 animals per group. In group 1 (control group) Ti6Al4 V bolts were implanted into the distal femur, in group 2 the Ti6Al4 V bolts were coated with four TiO2-coatings with integrated Cu(2+)-ions (4 × Cu-TiO2). Blood tests were performed weekly until the animals were sacrificed 4 weeks postoperative. The maximum peak of Cu and ceruloplasmin concentration could be seen in both groups one week postoperative, whereas the Cu values in group II were significantly higher. The Cu concentration in both groups approximated the initial basic values 4 weeks postoperative. The 4 × Cu-TiO2 coating tested in our rabbit model for total knee arthroplasty is an active coating that releases potentially antibacterial Cu(2+) for 4 weeks with a peak 1 week postoperative. The bioactive coating could be a promising approach for a use in the field of implant related infection, orthopaedic revision and tumor surgery in the future.
Cobalt-based materials are widely used for coronary stents, as well as bone and joint implants. However, their use is associated with high corrosion incidence. Titanium alloys, by contrast, are more biocompatible owing to the formation of a relatively inactive titanium oxide (TiO 2 ) layer on their surface. This study was aimed at improving Co28Cr6Mo alloy cytocompatibility via sol-gel TiO 2 coating to reduce metal corrosion and metal ion release. Owing to their role in inflammation and tissue remodelling around an implant, endothelial cells present a suitable in vitro model for testing the biological response to metallic materials. Primary human endothelial cells seeded on Co28Cr6Mo showed a stress phenotype with numerous F-actin fibres absent on TiO 2 -coated material. To investigate this effect at the gene expression level, cDNA microarray analysis of in total 1301 genes was performed. Compared with control cells, 247 genes were expressed differentially in the cells grown on Co28Cr6Mo, among them genes involved in proliferation, oxidative stress response and inflammation. TiO 2 coating reduced the effects of Co28Cr6Mo on gene expression in endothelial cells, with only 34 genes being differentially expressed. Quantitative real-time polymerase chain reaction and protein analysis confirmed microarray data for selected genes. The effect of TiO 2 coating can be, in part, attributed to the reduced release of Co 2þ , because addition of CoCl 2 resulted in similar cellular responses. TiO 2 coating of cobalt-based materials, therefore, could be used in the production of cobalt-based devices for cardiovascular and skeletal applications to reduce the adverse effects of metal corrosion products and to improve the response of endothelial and other cell types.
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