Antibacterial copper-filled TiO2 coating of cardiovascular implants to prevent infective endocarditis-A pilot study.

BACKGROUND: Infective endocarditis (IE) poses a significant health risk, especially in patients with prosthetic heart valves. Despite advances in treatment, mortality rates remain high. This study aims to investigate the antibacterial properties of a copper titanium dioxide (4× Cu-TiO2) coating on cardiovascular implants against Staphylococcus aureus, a common causative agent of IE. METHODS: Titanium oxide carriers functionalized with copper ions were employed as an antibacterial coating for heart and vascular prostheses. The coating's antibacterial efficacy was assessed using S. aureus ATCC 29213. Microscopic evaluations were conducted on both biological and artificial materials. Antibacterial activity was qualitatively assessed via a modified disc diffusion method and quantitatively measured through colony counts in NaCl suspensions. RESULTS: The coating process was successfully applied to all tested cardiovascular prosthetic materials. Qualitative assessments of antibacterial effectiveness revealed an absence of bacterial growth in the area directly beneath the coated valve. Quantitative evaluations showed a significant reduction in bacterial colonization on coated mechanical valves, with 2.95 × 104 CFU per valve, compared to 1.91 × 105 CFU in control valves. CONCLUSIONS: The 4× Cu-TiO2 coating demonstrated promising antibacterial properties against S. aureus, suggesting its potential as an effective strategy for reducing the risk of bacterial colonization of cardiovascular implants. Further studies are needed to assess the longevity of the coating and its efficacy against other pathogens.

Correction to: Bone defect reconstruction with a novel biomaterial containing calcium phosphate and aluminum oxide reinforcement.

An amendment to this paper has been published and can be accessed via the original article.

Bone defect reconstruction with a novel biomaterial containing calcium phosphate and aluminum oxide reinforcement.

BACKGROUND: Reconstruction of metaphyseal fractures represents a clinical challenge for orthopedic surgeons. Especially in osteoporotic bone, these fractures are frequently accompanied by osseous substance defects. In order to ensure rapid mobilization of patients, high stability requirements must be met by osteosynthesis. Various bone graft materials have been introduced in the past, such as autologous bone or exogenous bone substitute materials. These are used as bone void fillers or as augmentation techniques to ensure safe fixation of osteosynthesis. New calcium phosphate-based bone void-filling materials could be a promising alternative to autologous bone or to the currently and widely used polymethylmethacrylate (PMMA)-based cement. The aim of this study was to evaluate a novel paste-like bone void filler in vivo and in vitro with regard to biocompatibility and osteoconductivity. METHODS: In addition to in vitro testing of cell compatibility using pre-osteoblasts (MC3T3-E1), 35 Wistar rats were treated in vivo with implantation of various material mixtures based on calcium phosphate and aluminum oxide reinforcement in a metaphyseal drill hole defect. After 4 weeks, an examination by micro-computed tomography (µCT) and histology was performed. RESULTS: The in vitro analysis showed good biocompatibility with a high cell survival of osteoblasts. In the in vivo experiments, a significantly higher bone ingrowth compared to the empty defect was shown by µCT and histological analysis. Here, the group receiving material reinforced with aluminum oxide (Al2O3) showed a bone volume/tissue volume (BV/TV) of 89.19% compared to a BV/TV of 83.14% for the empty defect (p = 0.0013). In the group treated with a polysaccharide matrix, no increase in BV/TV was observed given a mean ratio of 80.14%. Scoring of histological sections did not reveal a significant difference between CaP and CaP that was substituted with Al2O3. CONCLUSION: The results of this study show an encouraging first step towards the development of new pasty, bone void-filling materials. We demonstrated that a new paste-like bone-filling material, based on calcium phosphate granulates and aluminum oxide to provide strength, exhibits good biocompatibility and osteoconductivity. Further biomechanical test in an osteoporotic animal model will have to be performed, to prove feasibility in metaphyseal defects.

A biocompatible sol-gel derived titania coating for medical implants with antibacterial modification by copper integration.

Implant-associated infections are dangerous complications and may cause dramatic illness with hematogeneous spread of bacteria and secondary infections. Since treatment of these infections remains most challenging and commonly requires implant removal, prevention is of utmost importance. In the present work a titania-sol was equipped with a copper salt resulting after calcination in a titania coating (TiO2) with antibacterial properties combined with good cytocompatibility. In vitro tests with bacteria as well as tissue cells were carried out under corresponding conditions. Mouse fibroblasts and different staphylococcal strains were used for growth inhibition assays with serial dilutions of CuCl2. Cultivation on the surface of bare Ti6Al4V, TiO2-coated and copper-filled TiO2-coated Ti6Al4V samples was performed with both bacteria and tissue cells. Bacterial and cellular proliferation and mitochondrial activity were hereby determined. Coating of Ti6Al4V with pure TiO2 significantly improved cytocompatibility compared to the uncoated alloy. In the growth inhibition assays, fibroblasts tolerated higher concentrations of copper ions than did bacteria. Nevertheless, copper integration reduced fibroblast proliferation and mitochondrial activity on the surface coating. On the other hand, integration of copper into the TiO2-coating significantly reduced adhesion of viable bacteria resulting in a promising combination of cytocompatibility and antibacterial properties. Additionally, significant bacterial growth inhibition by antibacterial amounts of copper was also demonstrated in the supernatant. In conclusion, the copper-loaded TiO2-coatings for medical implants may be a promising approach to reduce the rate of implant-associated infections.

Antibacterial Effect of a 4x Cu-TiO2 Coating Simulating Acute Periprosthetic Infection-An Animal Model.

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.

Release of Cu2+ from a copper-filled TiO2 coating in a rabbit model for total knee arthroplasty.

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.

Could titanium oxide coating from a sol-gel process make stone baskets more resistant to laser radiation at 2.1 µm?

BACKGROUND: Stone baskets could be easily destroyed by Holmium:YAG-laser at an endourologic treatment, with respect to this, we try to improve the resistance by coating them with a titanium oxide layer. The layer was established by a sol-gel-process. MATERIALS AND METHODS: Six new baskets (Equadus, Opi Med, Ettlingen, Germany) were used: 1.8 Ch. with 4 wires (diameter 0.127 mm). Three baskets were coated with a layer of titanium oxide established by a sol-gel process at the BioCerEntwicklungs GmbH in Bayreuth (~100 nanometres thickness). The lithotripter was a Holmium:YAG laser (Auriga XL, Starmedtec, Starnberg, Germany). 10 uncoated and 10 coated wires were tested with 610 mJ (the minimal clinical setting) and 2 uncoated and 2 coated wires were tested with 110 mJ. The wires were locked in a special holding instrument under water and the laser incident angle was 90°. The endpoint was gross visible damage to the wire and loss of electric conduction. RESULTS: Only two coated wires resisted two pulses (one in the 610 mJ and one in the 110 mJ setting). All other wires were destroyed after one pulse. CONCLUSION: This was the first attempt at making stone baskets more resistant to a Holmium:YAG laser beam. Titanium oxide deposited by a sol-gel-process on a titanium-nickel alloy did not result in better resistance to laser injuries.

An extended spectrum bactericidal titanium dioxide (TiO2) coating for metallic implants: in vitro effectiveness against MRSA and mechanical properties.

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.