The limited hemocompatibility of currently used oxygenator membranes prevents long-term use of artificial lungs in patients with lung failure. To improve hemocompatibility, we developed a novel covalent C1-esterase inhibitor (C1-INH) coating. Besides complement inhibition, C1-INH also prevents FXII activation, a very early event of contact phase activation at the crossroads of coagulation and inflammation. Covalently coated heparin, as the current anticoagulation gold standard, served as control. Additionally, a combination of both coatings (C1-INH/heparin) was established. The coatings were tested for their hemocompatibility by dynamic incubation with freshly drawn human whole blood. The analysis of various blood and plasma parameters revealed that C1-INH-containing coatings were able to markedly reduce FXIIa activity compared to heparin coating. Combined C1-INH/heparin coatings yielded similarly low levels of thrombin-antithrombin III complex formation as heparin coating. In particular, adhesion of monocytes and platelets as well as the diminished formation of fibrin networks were observed for combined coatings. We could show for the first time that a covalent coating with complement inhibitor C1-INH was able to ameliorate hemocompatibility. Thus, the early inhibition of the coagulation cascade is likely to have far-reaching consequences for the other cross-reacting plasma protein pathways.

Factor XII (FXII) is a zymogen present in blood that tends to adsorb onto the surfaces of blood‐contacting medical devices. Once adsorbed, it becomes activated, initiating a cascade of enzymatic reactions that lead to surface‐induced coagulation. This process is characterized by multiple redundancies, making it extremely challenging to prevent clot formation and preserve the properties of the surface. In this study, a novel modulatory coating system based on C1‐esterase inhibitor (C1INH) functionalized polymer brushes, which effectively regulates the activation of FXII is proposed. Using surface plasmon resonance it is demonstrated that this coating system effectively repels blood plasma proteins, including FXII, while exhibiting high activity against activated FXII and plasma kallikrein under physiological conditions. This unique property enables the modulation of FXII activation without interfering with the overall hemostasis process. Furthermore, through dynamic Chandler loop studies, it is shown that this coating significantly improves the hemocompatibility of polymeric surfaces commonly used in medical devices. By addressing the root cause of contact activation, the synergistic interplay between the antifouling polymer brushes and the modulatory C1INH is expected to lay the foundation to enhance the hemocompatibility of medical device surfaces.

During open heart surgery, the haemostasis status of a patient has to be monitored permanently in order to quickly and reliably detect bleeding or coagulation-based disorders. Currently, no single medical device is available to provide a comprehensive solution for monitoring the coagulation status (coagulation, platelets and fibrinolysis). We intend to approach this problem with a rheological method. Here, we compared the performance of an oscillatory rheometer with a medical reference device, a ball coagulometer. Measuring the extrinsic coagulation (prothrombin time; PT), various heparin concentrations (0.5–2.0 IU/mL) could be differentiated and also discriminated from the intrinsic coagulation (activated partial thromboplastin time; aPTT) providing comparable clotting times between rheometer and ball coagulometer. In addition, the oscillatory rheometer was capable to detect the antagonising of heparin with the equimolar concentration of protamine and also the titration of various protamine concentrations (0.5–3.0 IU/mL) to a fixed heparin concentration (2 IU/mL). The addition of increasing concentrations of heparin to citrated blood prolonged the clotting time (CT), changed the slope calculated by linear regression of the elastic and viscous shear moduli (i.e., information of the coagulation process) and changed the value of the shear moduli at the end of the measurement (300 s). These results indicate that the oscillatory rheometer is capable to dynamically measure the haemostasis status with different activators and various inhibitor concentrations.

During surgical procedures, cotton abdominal swabs with their high absorptive capacity and malleability are used to retain organs and absorb blood or other body fluids. Such properties of the natural material cotton are advantageous for most operations, but in cardiopulmonary bypass (CPB) surgery, a high blood volume can accumulate in the thoracic cavity that is quickly retransfused via the heart–lung machine (HLM). This common practice is supposed to be safe due to the high anticoagulation. However, in vitro analyses showed that blood cells and plasma proteins were activated despite a high anticoagulation, which can propagate especially an inflammatory response in the patient. Thus, we investigated patients’ blood during CPB surgery for inflammatory and coagulation-associated activation after contact to the HLM and either cotton or synthetic abdominal swabs. Contact with cotton significantly increased thrombocyte and neutrophil activation measured as β-thromboglobulin and PMN-elastase secretion, respectively, compared to synthetic abdominal swabs. Both inflammatory cytokines, interleukin (IL) 1β and IL6, were also significantly increased in the cotton over the synthetic patient group, while SDF-1α was significantly lower in the synthetic group. Our data show for the first time that cotton materials can activate platelets and leukocytes despite a high anticoagulation and that this activation is lower with synthetic materials. This additional activation due to the material on top of the activation exerted by the tissue contact that blood is exposed to during CPB surgery can propagate further reactions in patients after surgery, which poses a risk for this already vulnerable patient group.