Elucidating the pathway of thrombosis and inflammation in artificial lung devices using a proteomics approach

• Applicant: Sandra Stoppelkamp, Ph.D.
• Subject Area: Nuclear Medicine, Radiotherapy, Radiobiology ; Cardiac and Vascular Surgery
• Term: from 2017 to 2022
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 347306600

The concept of extracorporeal membrane oxygenation represents a crucial technological improvement for treatment of acute and chronic lung diseases. This now routinely used procedure is life-saving for patients with acute respiratory dystress syndrome and also a bridge-to-transplant solution. Despite the improved haemocompatibility and gas exchange properties of the membrane oxygenators, no long-term solution is currently available. This hinders the progress towards an implantable artificial lung as foreign body reactions within the oxygenator and tubings lead to e.g. activation of coagulation and complement system and inflammatory reactions. In the past decade, different coatings have significantly improved the haemocompatibility, but the oxygenators can rarely be used more than a few days. In part, the underlying cause for adverse/coagulation reactions in the oxygenators has been identified: plasma protein adsorption to the membranes occurs within seconds and the composition of adsorbed proteins as well as their conformation changes over time (Vroman effect). Ideally, the formed protein layer forms a neointima-like structure recognised as own and thus minimising adverse reactions. So far, an ideal protein layer has not been recognised or established. We therefore aim to elucidate the time-dependent thrombogenic and inflammatory pathway in model oxygenator devices with different promising coatings by a powerful proteomics approach (Progenesis LC-MS). A subsequent comparison of protein adsorption between oxygenators run with human whole blood from healthy donors and used patient oxygenators will further shed light into the thrombogenic events, especially with comorbidities. The results of our basic research will then be used to construct the proposed ideal oxygenator surface for long-term support.

• DFG Programme: Priority Programmes
• Subproject of: SPP 2014: Towards an Implantable Lung
• Co-Investigators: Professor Dr. Christian Schlensak; Professor Dr. Hans Peter Wendel