EndOxy-InFlame

 

EndOxy in Flame – Influence of a Biohybrid Lung on Inflammatory Pathways and Immune System-Endothelial Cell-Interaction

Extracorporeal membrane oxygenation, ECMO by short, is an adequate therapy for the treatment of acute lung failure mainly, the Acute Respiratory Distress Syndrome, ARDS, by short. It could serve as a suitable option in chronic lung failure, Chronic Obstructive Pulmonary Disease, COPD by short, as well, if the obstacles towards an implantable lung are cleared. However, the long-term use of ECMO systems and their development towards an implantable lung device is mainly limited by failure of the oxygenator device. This in turn is due to the poor hemocompatibility of the gas exchange membranes, which are in direct contact with the blood. As a result, unspecific protein binding to the gas exchange membrane leads to a significant decrease of gas transfer performance and thus, a replacement of the device is required after days to some weeks. In addition, the artificial material induces a systemic inflammatory response with yet undefined consequences for the human body.

Endothelial cell lining of the gas exchange membranes, so-called endothelialization, seems to be a promising approach to overcome these limitations and opens the gate towards an implantable lung EndOxy. The active endothelial cell layer acts as a natural bio interface for the contacting blood phase. Nevertheless, the role of the endothelial cell lining in such biohybrid systems with regard to acute and chronic inflammatory responses is currently unknown to our knowledge. Similarly, the reaction of the endothelial cell lining in the setting of low-grade inflammation in COPD and high-grade inflammation during ARDS and COPD exacerbations is unknown.

Therefore, the aim of the project is to study the effect of the endothelial cell layer on inflammation in peripheral blood and vice versa in homeostatic conditions, in low-grade and high-grade inflammatory conditions. To evaluate the inflammatory properties, we will analyze early signaling events combined with isolated blood and endothelial cells during ECMO in miniaturized biohybrid lung models. This will provide new information about superiority or inferiority of endothelialized devices regarding inflammation in acute and chronic conditions and will identify possible pathways that can be targeted by pharmaceutical approaches.

Partner	Prof. Dr. med. Klaus Tenbrock, University Hospital Aachen, Pediatric Clinic
Funding:	German Research Foundation (DFG) within Priority Program “Towards an Implantable Lung” (Link: https://www.ukaachen.de/kliniken-institute/klinik-fuer-anaesthesiologie/forschung/spp-towards-an-implantable-lung)