Nonthrombogenic active surface modification of oxygenator membranes for an extended event-free use

• Nicht-thrombogene aktive Oberflächenmodifikation von Oxygenator- Membranen für einen verlängerten komplikationsfreien Einsatz

Obstals, Fabian; Herrmann, Andreas (Thesis advisor); Rodriguez-Emmenegger, César (Thesis advisor)

Aachen : RWTH Aachen University (2023)
Dissertation / PhD Thesis

Dissertation, RWTH Aachen University, 2023

Abstract

Blood-contacting medical devices stand out due to their highly beneficial usage in modern medicine. These devices include catheters, stents, vascular grafts, heart valves, hemodialysis systems, and heart- lung replacement devices. Despite revolutionary advances in the field of biomaterial science during the last decades, complications are still common and range from impairment of the device functions, often leading to replacement, up to potential life-threatening scenarios for the patient. The contact of blood with any artificial surface leads to the inherent activation of blood coagulation and generally thrombosis which concomitantly causes other adverse complications. Unfortunately, no material or surface coating has yet been developed which truly merits the term ‘hemocompatible’ as endothelium does. The aim of this thesis was to introduce new concepts for bioactive surface modifications that mimic features of healthy endothelium. In order to achieve this elusive goal, several levels of functionality were constructed with the purpose of providing passive protection from undesired protein fouling (antifouling) and most importantly an adaptive bioactive mechanism (localized fibrinolysis) directly on the surface.Antifouling polymer brushes were synthesized on commercially available poly(4-methyl-1-pentene) (PMP) membranes that are currently used in extracorporeal membrane oxygenation (ECMO). The ability to resist nonspecific protein, platelet, and leukocyte adsorption was successfully evaluated and resulted in an overall improved hemocompatibility. Moreover, an innovative antifouling concept for the surface modification of larger and more complex substrates (e.g., hollow fiber membranes) was developed. The antifouling capabilities were evaluated to be comparable to the best grafted-from polymer brushes and combined with their feasible application on a plethora of materials, highlights the universal and scalable character of the antifouling strategy. The bioactivity of the surface modification was realized by inspiration of the only true hemocompatible surface available: healthy endothelium. Nature utilizes this powerful blood interface to perfectly control hemostasis and prevent uncontrolled thrombus formation. The developed coating system is composed of a polymer brush layer that resists nonspecific interaction with blood. Additionally, these brushes are further biofunctionalized with tissue-plasminogen activator (tPA) which enables this antifouling-bioactive surface modification to detect the condition of blood and, in consequence, to dictate blood to activate the inherent fibrinolysis. This leads to the unprecedented ability to lyse macroscopic clots even if the surface density of tPA is in the range of a few ng·cm-2.

Institutions

• DWI - Leibniz-Institut für Interaktive Materialien e.V. [052200]
• Department of Chemistry [150000]
• Chair of Macromolecular Materials and Systems [155910]