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.
The anticoagulation treatment of cardiovascular patients, which is mandatory after implantation of heart valves or stents, has significantly adverse effects on life quality. This treatment can be reduced or even circumvented by developing novel antithrombogenic surfaces of blood-contacting implants. Thus, we aim to discover materials exhibiting outstanding hemocompatibility compared to other available synthetic materials. We present promising surficial characteristics of single crystalline alumina in terms of platelet activation inhibition. In order to elucidate the relation between its crystallographic properties including the plane orientation and blood cell behavior, we examined endothelialization, cytocompatibility, and platelet activation at the blood-alumina interfaces in a controlled experimental setup. We observed that the cell response is highly sensitive to the plane orientation and differs significantly for (0001) and (11–20) planes of Al2O3. Our results reveal for the first time the dependence of platelet activation on crystallographic orientation, which is assumed to be a critical condition controlling the thrombogenicity. Additionally, we used an endothelial cell monolayer as an internal control since endothelial cells have an impact on vessel integrity and implant acceptance. We successfully demonstrate that Al2O3(11–20) exhibits enhanced hemocompatibility in contrast to Al2O3(0001) and is comparable to the physiological endothelial monolayer in vitro.
Hemocompatibility is the most significant criterion for blood-contacting materials in successful in vivo applications. Prior to the clinical tests, in vitro analyses must be performed on the biomaterial surfaces in accordance with the ISO 10993-4 standards.Designing a bio-functional material requires engineering the surface structure and chemistry, which significantly influence the blood cell activity according to earlier studies. In this study, we elucidate the role of surface terminations and polymorphs of SiC single crystals in the initial stage of the contact coagulation. We present a detailed analysis of phase, roughness, surface potential, wettability, consequently, reveal their effect on cytotoxicity and hemocompatibility by employing live/dead stainings, live cell imaging, ELISA and Micro BCA protein assay. Our results showed that the surface potential and the wettability strongly depend on the crystallographic polymorph as well as the surface termination. We show, for the first time, the key role of SiC surface termination on platelet activation. This dependency is in good agreement with the results of our in vitro analysis and points out the prominence of cellular anisotropy. We anticipate that our experimental findings bridge the surface properties to the cellular activities, and therefore, pave the way for tailoring advanced hemocompatible surfaces.
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