Utilization of a highly adaptable murine air pouch model for minimally invasive testing of the inflammatory potential of biomaterials.

Introduction: The biocompatibility of an implanted material strongly determines the subsequent host immune response. After insertion into the body, each medical device causes tissue reactions. How intense and long-lasting these are is defined by the material properties. The so-called foreign body reaction is a reaction leading to the inflammation and wound healing process after implantation. The constantly expanding field of implant technology and the growing areas of application make optimization and adaptation of the materials used inevitable. Methods: In this study, modified liquid silicone rubber (LSR) and two of the most commonly used thermoplastic polyurethanes (TPU) were compared in terms of induced inflammatory response in the body. We evaluated the production of inflammatory cytokines, infiltration of inflammatory cells and encapsulation of foreign bodies in a subcutaneous air-pouch model in mice. In this model, the material is applied in a minimally invasive procedure via a cannula and in one piece, which allows material testing without destroying or crushing the material and thus studying an intact implant surface. The study design includes short-term (6 h) and long-term (10 days) analysis of the host response to the implanted materials. Air-pouch-infiltrating cells were determined by flow cytometry after 6 h and 10 days. Inflammation, fibrosis and angiogenesis markers were analyzed in the capsular tissue by qPCR after 10 days. Results: The foreign body reaction was investigated by macroscopic evaluation and scanning electron microscopy (SEM). Increased leukocyte infiltration was observed in the air-pouch after 6 h, but it markedly diminished after 10 days. After 10 days, capsule formations were observed around the materials without visible inflammatory cells. Discussion: For biocompatibility testing materials are often implanted in muscle tissue. These test methods are not sufficiently conclusive, especially for materials that are intended to come into contact with blood. Our study primarily shows that the presented model is a highly adaptable and minimally invasive test system to test the inflammatory potential of and foreign body reaction to candidate materials and offers more precise analysis options by means of flow cytometry.

Bacterial Adhesion and Biofilm Formation of Enterococcus faecalis on Zwitterionic Methylmethacrylat and Polysulfones.

Biofilm-associated implant infections represent a major challenge for healthcare systems around the world due to high patient burden and enormous costs incurred. Enterococcus faecalis (E. faecalis) is the most prevalent enterococcal species identified in biofilm-associated infections. The steadily growing areas of application of implants demand a solution for the control of bacterial infections. Therefore, the development of modified anti-microbial implant materials and the testing of the behavior of different relevant bacterial strains towards them display an indispensable task. Recently, we demonstrated an anti-microbial effect of zwitterionic modified silicone rubber (LSR) against Staphylococcus aureus. The aim of this study was to evaluate bacterial colonization and biofilm formation of another clinically relevant strain, E. faecalis, on this material in comparison to two of the most commonly used thermoplastic polyurethanes (TPUs) and other modified LSR surfaces. By generating growth curves, crystal violet, and fluorescence staining, as well as analyzing the expression of biofilm-associated genes, we demonstrated no anti-microbial activity of the investigated materials against E. faecalis. These results point to the fact that anti-microbial effects of novel implant materials do not always apply across the board to all bacterial strains.

In Vitro Study of the Interaction of Innate Immune Cells with Liquid Silicone Rubber Coated with Zwitterionic Methyl Methacrylate and Thermoplastic Polyurethanes.

The biocompatibility of medical devices, such as implants and prostheses, is strongly determined by the host's immune response to the implanted material. Monocytes and macrophages are main actors of the so-called foreign body reaction. The innate immune system macrophages (M) can be broadly classified into the pro-inflammatory M1-type and the anti-inflammatory, pro-healing M2-type. While a transient inflammatory initial state can be helpful during an infection, persistent inflammation interferes with proper healing and subsequent regeneration. The functional orientation of the immune response, mirrored by monocyte polarization, during interaction with different biomaterials has not yet been sufficiently explored. In implant manufacturing, thermoplastic polyurethane (TPU) represents the state-of-the-art material. The constantly growing areas of application and the associated necessary adaptations make the optimization of these materials indispensable. In the present study, modified liquid silicone rubber (LSR) were compared with two of the most commonly used TPUs, in terms of monocyte adhesion and M1/M2 polarization in vitro. Human monocytes isolated from venous blood were evaluated for their ability to adhere to various biomaterials, their gene expression profile, and their cytokine release. Based on the results, the different polymers exhibit different potential to bias monocytes with respect to early pro-inflammatory cytokine production and gene transcription. Furthermore, none of our test materials showed a clear trend towards M1 or M2 polarization. However, we were able to evaluate the inflammatory potential of the materials, with the classic TPUs appearing to be the most unreactive compared to the silicone-based materials.

The Use of Zwitterionic Methylmethacrylat Coated Silicone Inhibits Bacterial Adhesion and Biofilm Formation of Staphylococcus aureus.

In recent decades, biofilm-associated infections have become a major problem in many medical fields, leading to a high burden on patients and enormous costs for the healthcare system. Microbial infestations are caused by opportunistic pathogens which often enter the incision already during implantation. In the subsequently formed biofilm bacteria are protected from the hosts immune system and antibiotic action. Therefore, the development of modified, anti-microbial implant materials displays an indispensable task. Thermoplastic polyurethane (TPU) represents the state-of-the-art material in implant manufacturing. Due to the constantly growing areas of application and the associated necessary adjustments, the optimization of these materials is essential. In the present study, modified liquid silicone rubber (LSR) surfaces were compared with two of the most commonly used TPUs in terms of bacterial colonization and biofilm formation. The tests were conducted with the clinically relevant bacterial strains Staphylococcus aureus and Staphylococcus epidermidis. Crystal violet staining and scanning electron microscopy showed reduced adhesion of bacteria and thus biofilm formation on these new materials, suggesting that the investigated materials are promising candidates for implant manufacturing.

Gold-tip electrodes--a new "deep lesion" technology for catheter ablation? In vitro comparison of a gold alloy versus platinum-iridium tip electrode ablation catheter.

Gold-tip electrodes. Radiofrequency (RF) catheter ablation is widely used to induce focal myocardial necrosis using the effect of resistive heating through high-frequency current delivery. It is current standard to limit the target tissue-electrode interface temperature to a maximum of 60-70 degrees C to avoid char formation. Gold (Au) exhibits a thermal conductivity of nearly four times greater than platinum (Pt-Ir) (3.17 W/cm Kelvin vs 0.716 W/cm Kelvin), it was therefore hypothesized that RF ablation using a gold electrode would create broader and deeper lesions as a result of a better heat conduction from the tissue-electrode interface and additional cooling of the gold electrode by "heat loss" to the intracardiac blood. Both mechanisms would allow applying more RF power to the tissue before the electrode-tissue interface temperature limit is reached. To test this hypothesis, we performed in vitro isolated liver and pig heart investigations comparing lesion depths of a new Au-alloy-tip electrode to standard Pt-Ir electrode material. Mean lesion depth in liver tissue for Pt-Ir was 4.33+/-0.45 mm (n=60) whereas Au electrode was able to achieve significantly deeper lesions (5.86+/-0.37 mm [n=60; P<0.001]). The mean power delivered using Pt-Ir was 6.95+/-2.41 W whereas Au tip electrode delivered 9.64+/-3.78 W indicating a statistically significant difference (P<0.05). In vitro pig heart tissue Au ablation (n=20) increased significantly the lesion depth (Au: 4.85+/-1.01 mm, Pt-Ir: 2.96+/-0.81 mm, n=20; P<0.001). Au tip electrode again applied significantly more power (P<0.001). Gold-tip electrode catheters were able to induce deeper lesions using RF ablation in vitro as compared to Pt-Ir tip electrode material. In liver and in pig heart tissue, the increase in lesion depth was associated with a significant increase in the average power applied with the gold electrode at the same level of electrode-tissue temperature as compared to platinum material.