Analysis of the Release Characteristics of Cu-Treated Antimicrobial Implant Surfaces Using Atomic Absorption Spectrometry

New developments of antimicrobial implant surfaces doped with copper (Cu) ions may minimize the risk of implant-associated infections. However, experimental evaluation of the Cu release is influenced by various test parameters. The aim of our study was to evaluate the Cu release characteristics in vitro according to the storage fluid and surface roughness. Plasma immersion ion implantation of Cu (Cu-PIII) and pulsed magnetron sputtering process of a titanium copper film (Ti-Cu) were applied to titanium alloy (Ti6Al4V) samples with different surface finishing of the implant material (polished, hydroxyapatite and corundum blasted). The samples were submersed into either double-distilled water, human serum, or cell culture medium. Subsequently, the Cu concentration in the supernatant was measured using atomic absorption spectrometry. The test fluid as well as the surface roughness can alter the Cu release significantly, whereby the highest Cu release was determined for samples with corundum-blasted surfaces stored in cell medium

A model of implant-associated infection in the tibial metaphysis of rats

Objective. Implant-associated infections remain serious complications in orthopaedic and trauma surgery. A main scientific focus has thus been drawn to the development of anti-infective implant coatings. Animal models of implant-associated infections are considered helpful in the in vivo testing of new anti-infective implant coatings. The aim of the present study was to evaluate a novel animal model for generation of implant-associated infections in the tibial metaphysis of rats. Materials and Methods. A custom-made conical implant made of Ti6Al4V was inserted bilaterally at the medial proximal tibia of 26 female Sprague-Dawley rats. Staphylococcus aureus in amounts spanning four orders of magnitude and each suspended in 15 l phosphate buffered saline (PBS) was inoculated into the inner cavity of the implant after the implantation into the defined position. Controls were treated accordingly with PBS alone. Animals were then followed for six weeks until sacrifice. Implant-associated infection was evaluated by microbiological investigation using swabs and determination of viable bacteria in the bone around the implant and the biofilm on the implants after sonification. Results. Irrespective of the initial inoculum, all animals in the various groups harbored viable bacteria in the intraoperative swabs as well as the sonication fluid of the implant and the bone samples. No correlation could be established between initially inoculated CFU and population sizes on implant surfaces at sacrifice. However, a significantly higher viable count was observed from peri-implant bone samples for animals inoculated with 10 6 CFU. Macroscopic signs of animal infection (pus and abscess formation) were only observed for implants inoculated with at least 10 5 CFU S. aureus. Discussion/Conclusion. The results demonstrate the feasibility of this novel animal model to induce an implant-associated infection in the metaphysis of rats, even with comparatively low bacterial inocula. The specific design of the implant allows an application of bacteria in reproducible numbers at well-defined contact sites to the animal bone

Impact of Cerebral Microbleeds in Stroke Patients with Atrial Fibrillation

OBJECTIVES: Cerebral microbleeds are associated with the risks of ischemic stroke and intracranial hemorrhage, causing clinical dilemmas for antithrombotic treatment decisions. We aimed to evaluate the risks of intracranial hemorrhage and ischemic stroke associated with microbleeds in patients with atrial fibrillation treated with Vitamin K antagonists, direct oral anticoagulants, antiplatelets, and combination therapy (i.e. concurrent oral anticoagulant and antiplatelet) METHODS: We included patients with documented atrial fibrillation from the pooled individual patient data analysis by the Microbleeds International Collaborative Network. Risks of subsequent intracranial hemorrhage and ischemic stroke were compared between patients with and without microbleeds, stratified by antithrombotic use. RESULTS: A total of 7,839 patients were included. The presence of microbleeds was associated with an increased relative risk of intracranial hemorrhage (aHR 2.74, 95% confidence interval 1.76 - 4.26) and ischemic stroke (aHR 1.29, 95% confidence interval 1.04 - 1.59). For the entire cohort, the absolute incidence of ischemic stroke was higher than intracranial hemorrhage regardless of microbleeds burden. However, for the subgroup of patients taking combination of anticoagulant and antiplatelet therapy, the absolute risk of intracranial hemorrhage exceeded that of ischemic stroke in those with 2-4 microbleeds (25 vs 12 per 1,000 patient-years) and ≥11 microbleeds (94 vs 48 per 1,000 patient-years). INTERPRETATION: Patients with atrial fibrillation and high burden of microbleeds receiving combination therapy have a tendency of higher rate of intracranial hemorrhage than ischemic stroke, with potential for net harm. Further studies are needed to help optimize stroke preventive strategies in this high-risk group. This article is protected by copyright. All rights reserved

A Comparison of Wear Patterns on Retrieved and Simulator-Tested Total Knee Replacements

Aseptic implant loosening is the most common reason for revision surgery after total knee replacement. This is associated with adverse biological reactions to wear debris from the articulating implant components. To predict the amount of wear debris generated in situ, standard wear testing of total knee replacement (TKR) is carried out before its clinical use. However, wear data reported on retrievals of total knee replacement (TKR) revealed significant discrepancies compared with standard wear simulator studies. Therefore, the aim of the present study was to compare the wear patterns on identical posterior-cruciate-retaining TKR designs by analyzing retrieved and experimentally tested implants. The identification and classification of wear patterns were performed using 21 retrieved ultra-high-molecular-weight-polyethylene (UHMW-PE) inserts and four sets of inserts of identical design and material tested in a knee wear simulator. These four sets had undergone different worst-case conditions and a standard test in a wear simulator according to ISO 14243-1. Macroscopic and microscopic examinations of the polyethylene inserts were performed, including the determination of seven modes of wear that correspond to specific wear patterns, the calculation of wear areas, and the classification of the damage over the whole articulating area. Retrieved and standard wear simulator-tested UHMW-PE inserts showed significant differences in wear area and patterns. The total wear areas and the damage score were significantly larger on the retrievals (52.3% versus 23.9%, 32.7 versus 22.7). Furthermore, the range of wear patterns found on the retrievals was not reproducible in the simulator-tested inserts. However, good correspondence was found with the simulator-tested polyethylene inserts under worst-case conditions (third body wear), i.e., deep wear areas could be replicated according to the in vivo situation compared with other wear test scenarios. Based on the findings presented here, standard simulator testing can be used to directly compare different TKR designs but is limited in the prediction of their in situ wear. Preclinical wear testing may be adjusted by worst-case conditions to improve the prediction of in situ performance of total knee implants in the future

Wear Performance of Sequentially Cross-Linked Polyethylene Inserts against Ion-Treated CoCr, TiNbN-Coated CoCr and Al2O3 Ceramic Femoral Heads for Total Hip Replacement

The aim of the present study was to evaluate the biotribology of current surface modifications on femoral heads in terms of wettability, polyethylene wear and ion-release behavior. Three 36 mm diameter ion-treated CoCr heads and three 36 mm diameter TiNbN-coated CoCr heads were articulated against sequentially cross-linked polyethylene inserts (X3) in a hip joint simulator, according to ISO 14242. Within the scope of the study, the cobalt ion release in the lubricant, as well as contact angles at the bearing surfaces, were investigated and compared to 36 mm alumina ceramic femoral heads over a period of 5 million cycles. The mean volumetric wear rates were 2.15 ± 0.18 mm3·million cycles−1 in articulation against the ion-treated CoCr head, 2.66 ± 0.40 mm3·million cycles−1 for the coupling with the TiNbN-coated heads and 2.17 ± 0.40 mm3·million cycles−1 for the ceramic heads. The TiNbN-coated femoral heads showed a better wettability and a lower ion level in comparison to the ion-treated CoCr heads. Consequently, the low volumes of wear debris, which is comparable to ceramics, and the low concentration of metal ions in the lubrication justifies the use of coated femoral heads

Experimental Investigation of Material Transfer on Bearings for Total Hip Arthroplasty—A Retrieval Study on Ceramic and Metallic Femoral Heads

Metallic deposition is a commonly observed phenomenon on the surface of revised femoral heads in total hip arthroplasty and can lead to increased wear due to third bodies. In order to find out the origin and composition of the transfer material, 98 retrieved femoral heads of different materials were examined with regard to the cause of revision, localization, pattern and composition of the transfer material by energy dispersive X-ray spectroscopy. We found that in 53.1%, the deposition was mostly in the region of the equator and the adjacent pole of the femoral heads. The most common cause for revision of heads with metallic deposition was polyethylene wear (43.9%). Random stripes (44.9%), random patches (41.8%) and solid patches (35.7%) were most prevalent on retrieved femoral heads. Random patches were a typical pattern in ceramic-on-ceramic bearing couples. The solid patch frequently occurred in association with dislocation of the femoral head (55%). The elemental analysis of the depositions showed a variety of different materials. In most cases, titanium was an element of the transferred material (76.5%). In addition to metallic components, several non-metallic components were also detected, such as carbon (49%) or sulfur (4.1%). Many of the determined elements could be assigned with regard to their origin with the help of the associated revision cause. Since the depositions lead to an introduction of third-body particles and thus to increased wear, the depositions on the bearing surfaces should be avoided in any case

Quantification of Osseointegration of Plasma-Polymer Coated Titanium Alloyed Implants by means of Microcomputed Tomography versus Histomorphometry

A common method to derive both qualitative and quantitative data to evaluate osseointegration of implants is histomorphometry. The present study describes a new image reconstruction algorithm comparing the results of bone-to-implant contact (BIC) evaluated by means of µCT with histomorphometry data. Custom-made conical titanium alloyed (Ti6Al4V) implants were inserted in the distal tibial bone of female Sprague-Dawley rats. Different surface configurations were examined: Ti6Al4V implants with plasma-polymerized allylamine (PPAAm) coating and plasma-polymerized ethylenediamine (PPEDA) coating as well as implants without surface coating. After six weeks postoperatively, tibiae were explanted and BIC was determined by µCT (3D) and afterwards by histomorphometry (2D). In comparison to uncoated Ti6Al4V implants demonstrating low BIC of 32.4% (histomorphometry) and 51.3% (µCT), PPAAm and PPEDA coated implants showed a nonsignificant increase in BIC (histomorphometry: 45.7% and 53.5% and µCT: 51.8% and 62.0%, resp.). Mean BIC calculated by µCT was higher for all surface configurations compared to BIC detected by histomorphometry. Overall, a high correlation coefficient of 0.70 (p<0.002) was found between 3D and 2D quantification of BIC. The μCT analysis seems to be suitable as a nondestructive and accurate 3D imaging method for the evaluation of the bone-implant interface

A Cell-Adhesive Plasma Polymerized Allylamine Coating Reduces the In Vivo Inflammatory Response Induced by Ti6Al4V Modified with Plasma Immersion Ion Implantation of Copper

Copper (Cu) could be suitable to create anti-infective implants based on Titanium (Ti), for example by incorporating Cu into the implant surface using plasma immersion ion implantation (Cu-PIII). The cytotoxicity of Cu might be circumvented by an additional cell-adhesive plasma polymerized allylamine film (PPAAm). Thus, this study aimed to examine in vivo local inflammatory reactions for Ti6Al4V implants treated with Cu-PIII (Ti-Cu), alone or with an additional PPAAm film (Ti-Cu-PPAAm), compared to untreated implants (Ti). Successful Cu-PIII and PPAAm treatment was confirmed with X-ray Photoelectron Spectroscopy. Storage of Ti-Cu and Ti-Cu-PPAAm samples in double-distilled water for five days revealed a reduction of Cu release by PPAAm. Subsequently, Ti, Ti-Cu and Ti-Cu-PPAAm samples were simultaneously implanted into the neck musculature of 24 rats. After 7, 14 and 56 days, peri-implant tissue was retrieved from 8 rats/day for morphometric immunohistochemistry of different inflammatory cells. On day 56, Ti-Cu induced significantly stronger reactions compared to Ti (tissue macrophages, antigen-presenting cells, T lymphocytes) and to Ti-Cu-PPAAm (tissue macrophages, T lymphocytes, mast cells). The response for Ti-Cu-PPAAm was comparable with Ti. In conclusion, PPAAm reduced the inflammatory reactions caused by Cu-PIII. Combining both plasma processes could be useful to create antibacterial and tissue compatible Ti-based implants

Evaluation of Osseointegration of Titanium Alloyed Implants Modified by Plasma Polymerization

By means of plasma polymerization, positively charged, nanometre-thin coatings can be applied to implant surfaces. The aim of the present study was to quantify the adhesion of human bone cells in vitro and to evaluate the bone ongrowth in vivo, on titanium surfaces modified by plasma polymer coatings. Different implant surface configurations were examined: titanium alloy (Ti6Al4V) coated with plasma-polymerized allylamine (PPAAm) and plasma-polymerized ethylenediamine (PPEDA) versus uncoated. Shear stress on human osteoblast-like MG-63 cells was investigated in vitro using a spinning disc device. Furthermore, bone-to-implant contact (BIC) was evaluated in vivo. Custom-made conical titanium implants were inserted at the medial tibia of female Sprague-Dawley rats. After a follow-up of six weeks, the BIC was determined by means of histomorphometry. The quantification of cell adhesion showed a significantly higher shear stress for MG-63 cells on PPAAm and PPEDA compared to uncoated Ti6Al4V. Uncoated titanium alloyed implants showed the lowest BIC (40.4%). Implants with PPAAm coating revealed a clear but not significant increase of the BIC (58.5%) and implants with PPEDA a significantly increased BIC (63.7%). In conclusion, plasma polymer coatings demonstrate enhanced cell adhesion and bone ongrowth compared to uncoated titanium surfaces