Fabian Obstals

Interfacing blood with any artificial surface instantly triggers the activation of coagulation at the interface, posing a risk of adverse thromboembolic complications. Immediately upon contact, blood proteins adsorb to the surface turning it into an active prothrombogenic and proinflammatory interface promoting the activation of platelets and the coagulation cascade. Here, an interactive hemocompatible nanocoating is designed that synergistically combines antifouling polymer brushes with the activity of an anti‐FXIIa antibody to tackle the two main causes of surface‐induced coagulation. The brushes provide a passive layer rendering the surface stealth and non‐thrombogenic against blood activation. Furthermore, as soon as traces of FXIIa arise, the coating immediately and specifically scavenges it, thus actively switching‐off contact activation right at the beginning. Moreover, a means is developed to translate this coating to a broad range of polymeric surfaces commonly used in medical devices. The coated surfaces prevent protein adsorption and provide a barrier to bacterial colonization while being capable of capturing biologically relevant concentrations of FXIIa. Notably, the coating completely prevents the formation of clots on the surface when exposed to blood. Thus, the interactive anti‐FXIIa nanocoating provides a new avenue to improve the hemocompatibility of medical devices in a safe and efficient manner.

The ability of proteins to adsorb irreversibly onto surfaces opens new possibilities to functionalize biological interfaces. Herein, the mechanism and kinetics of adsorption of protein‐polymer macromolecules with the ability to equip surfaces with antifouling properties are investigated. These macromolecules consist of the liquid chromatography peak I peptide from which antifouling polymer brushes are grafted using single electron transfer‐living radical polymerization. Surface plasmon resonance spectroscopy reveals an adsorption mechanism that follows a Langmuir‐type of binding with a strong binding affinity to gold. X‐ray reflectivity supports this by proving that the binding occurs exclusively by the peptide. However, the lateral organization at the surface is directed by the cylindrical eGFP. The antifouling functionality of the unimolecular coatings is confirmed by contact with blood plasma. All coatings reduce the fouling from blood plasma by 8894% with only minor effect of the degree of polymerization for the studied range (DP between 101 and 932). The excellent antifouling properties, combined with the ease of polymerization and the straightforward coating procedure make this a very promising antifouling concept for a multiplicity of applications.

Nature utilizes endothelium as a blood interface that perfectly controls hemostasis, preventing the uncontrolled formation of thrombi. The management of positive and negative feedback that finely tunes thrombosis and fibrinolysis is essential for human life, especially for patients who undergo extracorporeal circulation (ECC) after a severe respiratory or cardiac failure. The exposure of blood to a surface different from healthy endothelium inevitably initiates coagulation, drastically increasing the mortality rate by thromboembolic complications. In the present study, an ultrathin antifouling fibrinolytic coating capable of disintegrating thrombi in a self-regulated manner is reported. The coating system is composed of a polymer brush layer that can prevent any unspecific interaction with blood. The brushes are functionalized with a tissue plasminogen activator (tPA) to establish localized fibrinolysis that solely and exclusively is active when it is required. This interactive switching between the dormant and active state is realized through an amplification mechanism that increases (positive feedback) or restores (negative feedback) the activity of tPA depending on whether a thrombus is detected and captured or not. Thus, only a low surface density of tPA is necessary to lyse real thrombi. Our work demonstrates the first report of a coating that self-regulates its fibrinolytic activity depending on the conditions of blood.