Biocompatibility testing of composite biomaterial designed for a new petal valve construction for pulsatile ventricular assist device.

This paper presents the results of biocompatibility testing performed on several biomaterial variants for manufacturing a newly designed petal valve intended for use in a pulsatile ventricular assist device or blood pump. Both physical vapor deposition (PVD) and plasma-enhanced chemical vapor deposition (PECVD) were used to coat titanium-based substrates with hydrogenated tetrahedral amorphous carbon (ta-C:H) or amorphous hydrogenated carbon (a-C:H and a-C:H, N). Experiments were carried out using whole human blood under arterial shear stress conditions in a cone-plate analyzer (ap. 1800 1/s). In most cases, tested coatings showed good or very good haemocompatibility. Type a-C:H, N coating proved to be superior in terms of activation, risk of aggregation, and the effects of generating microparticles of apoptotic origin, and also demonstrated excellent mechanical properties. Therefore, a-C:H, N coatings were selected for further in vivo studies. In vivo animal studies were carried out according to the ISO 10993 standard. Intradermal reactivity was assessed in three rabbits and sub-acute toxicity and local effects after implantation were examined in 12 rabbits. Based on postmortem examination, no organ failure or wound tissue damage occurred during the required period of observation. In summary, our investigations demonstrated high biocompatibility of the biomaterials in relation to thrombogenicity, toxicity, and wound healing. Prototypes of the petal valves were manufactured and mounted on the pulsatile ventricular assist device. Hydrodynamic features and impact on red blood cells (hemolysis) as well as coagulation (systemic thrombogenicity) were assessed in whole blood.

Biomimetics in thin film design: Niche-like wrinkles designed for i-cell progenitor cell differentiation.

The future and development of science are in interdisciplinary areas, such as biomedical engineering. Self-assembled structures, similar to stem cell niches, inhibit rapid cellular division processes and enable the capture of stem cells from blood flow. By modifying the surface topography and stiffness properties, progenitor cells were differentiated towards the formation of endothelial cell monolayers to effectively inhibit the coagulation cascade. Wrinkled material layers in the form of thin polymeric coatings were prepared. An optimized surface topography led to proper cell differentiation and influenced the appropriate formation of endothelial cell monolayers. Blood activation was decelerated by the formed endothelium.

Effects of the surface modification of polyurethane substrates on genotoxicity and blood activation processes.

The aim of this study was to determine the mutagenic and thrombogenic potential of a material composed of a thin coating deposited on a polymeric substrate. In this work, a surface was modified in a manner that would mimic the function of cellular niches. Finally, the surfaces should actively capture and differentiate progenitor cells from the blood stream. Thin films with 10 to 500nm thicknesses were deposited by unbalanced, pulsed DC magnetron sputtering on smooth polyurethane. Such high energy conditions led to a stiffening of the polymer surface layers by pseudodiffusion during the initial stages of film growth. Both the high intrinsic film stress due to high energy film growth and the huge difference in the elastic properties of the films and polymer substrates resulted in hierarchical and self-adapting nanowrinkling. Surface modifications of synthetic materials for future use in regeneration of the circulatory system must be tested in terms of their thrombogenicity and mutagenicity. Point mutations in many cases can lead to many serious haematologic complications. Genotoxicity was determined by testing for reverse histidine mutations in selected strains of Salmonella typhimurium. The analysis was performed in the presence and absence of metabolic activation system S9 containing liver microsomal fraction of rats. Based on these results, no mutagenicity of the tested material was observed. The interaction of blood and the material under dynamic conditions was described. Blood from above the analysed surface was collected after the test, and the quality of the blood was assessed along with the type of cellular response to the surface. In the obtained results of the coagulation processes, it was found that the tested material reduced the process of platelet activation under hydrodynamic conditions in comparison to the control material, polyurethane.

In vitro hemocompatibility on thin ceramic and hydrogel films deposited on polymer substrate performed in arterial flow conditions.

Hydrogel coatings were stabilized by titanium carbonitride a-C:H:Ti:N buffer layers deposited directly onto the polyurethane (PU) substrate beneath a final hydrogel coating. Coatings of a-C:H:Ti:N were deposited using a hybrid method of pulsed laser deposition (PLD) and magnetron sputtering (MS) under high vacuum conditions. The influence of the buffer a-C:H:Ti:N layer on the hydrogel coating was analysed by means of a multi-scale microstructure study. Mechanical tests were performed at an indentation load of 5 mN using Berkovich indenter geometry. Haemocompatible analyses were performed in vitro using a blood flow simulator. The blood-material interaction was analysed under dynamic conditions. The coating fabrication procedure improved the coating stability due to the deposition of the amorphous titanium carbonitride buffer layer.

Hemocompatible, pulsed laser deposited coatings on polymers.

State-of-the-art non-thrombogenic blood contacting surfaces are based on heparin and struggle with the problem of bleeding. However, appropriate blood flow characteristics are essential for clinical application. Thus, there is increasing demand to develop new coating materials for improved human body acceptance. Materials deposited by vacuum coating techniques would be an excellent alternative if the coating temperatures can be kept low because of the applied substrate materials of low temperature resistance (polymers). Most of the recently used plasma-based deposition techniques cannot fulfill this demand. However, adequate film structure and high adhesion can be reached by the pulsed laser deposition at room temperature, which was developed to an industrial-scaled process at Laser Center Leoben. Here, this process is described in detail and the resulting structural film properties are shown for titanium, titanium nitride, titanium carbonitride, and diamond-like carbon on polyurethane, titanium and silicon substrates. Additionally, we present the biological response of blood cells and the kinetic mechanism of eukaryote cell attachment. In conclusion, high biological acceptance and distinct differences for the critical delamination shear stress were found for the coatings, indicating higher adhesion at higher carbon contents.