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Cytocompatibility and hemocompatibility are essential features for tissue- and blood-contacting implants such as artificial heart valves, vascular grafts and stents. Platelet activation as the main trigger of thrombosis results in implant failures. The purpose of this study results from the demands on anti-coagulant and non-corrosive innovative biomaterials for cardiovascular implants. Therefore, hemocompatibility and cytocompatibility of various high-strength ceramics, such as alumina, zirconia, silicon nitride and silicon carbide, were examined to identify the most appropriate ceramic for cardiovascular implants. In addition to the material species, different crystallographic structures (single- and poly-crystalline) and surface terminations (Si and C faces) of silicon carbide were used in order to reveal the interactions between blood and material surface. Three cell types, i.e. human umbilical vein endothelial cells, mesenchymal stem cells and blood cells, were cultured on the substrates and their interactions with material surfaces were analyzed. Cytotoxicity of the materials was tested by live/dead staining. Hemocompatibility in terms of platelet and white blood cell activation was examined via scanning electron microscopy and indirect ELISA. To mimic physiological conditions in vitro, the hemocompatibility of the materials was additionally analyzed in a bioreactor under dynamic flow conditions in comparison to static incubation. All ceramics were found to be cytocompatible for mesenchymal stem cells, human umbilical vein endothelial cells and blood cells. The highest number of resting, non-activated platelets was observed on the monocrystalline silicon carbide demonstrating that this material triggers the platelet activation less compared to the other materials. It is found to be the most appropriate ceramic for blood-contacting implants in terms of cell adhesion, cell viability, and hemocompatibility. [ABSTRACT FROM AUTHOR]

[Display omitted] • GO can functionalize inert zirconia surfaces by covalent immobilization. • GO nanofilm provides wettability and osteogenic character to zirconia implants. • GO coating on bioinert ceramics improves osteogenic differentiation of MSC. • Novel GO-film is full-covering, homogeneous, hydrophilic, and hydrolytically stable. This study aimed to join the proven osteogenic properties of graphene oxide (GO) with bioinert zirconia implants. The dip-coating technique allows achieving this goal by forming a thin, homogenous, hydrolytically, and mechanically stable GO film onto silanized ceramic-substrates. SEM, AFM, XPS, and contact angle measurements confirmed the presence, transparency, integrity, and homogenous covering character of the GO film. The GO film is hydrolytically stable since it remained intact after a soaking period of 24 days in double-distilled water (ddH 2 O) and phosphate buffered saline and resisted a ten-minute sonication treatment for in ddH 2 O. This strong hydrolytic stability is due to the silanization with 3-amino-propyl-diisopropylethoxy-silane (APDS) enhancing the anchoring of GO flakes onto zirconia surfaces. Besides, the GO film disinfectable in 70% ethanol. Subsequently, we assessed our immobilized GO film as cytocompatible for L929 mouse fibroblast and human mesenchymal stem cells and propitious for the osteogenic differentiation demonstrated by a two times upregulation of the osteogenic transcription factor RunX2. The active hydroxyl and carboxyl groups of the GO film open new perspectives for the functionalization of ceramic implants by immobilization of biological agents, such as growth factors or antibiotics, and thus enhance the osseointegration. [ABSTRACT FROM AUTHOR]