EndOxy - Development of a biohybrid artificial lung

 

Background

Chronic airway disease is the third most frequent cause of mortality worldwide with chronic obstructive pulmonary disease (COPD) representing the major share of 4.2 million deaths in 2008. Patients developing chronic hypercapnia have a chance to die within five years. Ultimately, a lung transplantation remains the only long-term therapy available. However, the lack of donor organ resulting in long waiting list periods and waiting list mortality increases the undeniable need for a reliable technical alternative as an artificial lung.

Today, artificial lungs come in the form of extracorporal membrane oxygenators which are used for cardiopulmonary bypass as well as for long-term applications in the case of chronic lung diseases. However, the use of current ECMO devices is restricted to a few weeks at maximum which is mainly caused by hemoincompatibilities. Inside the oxygenator, large artificial surfaces cause platelet adhesion and blood clogging, finally leading to thrombosis. Therefore, severe anticoagulation is needed to slow down this process, causing bleeding events on the other hand. An endothelialized oxygenator is supposed to resemble the physiological environment inside lungs and should prevent all the stated complications. Moreover, in the long run this would be the necessary first step towards a completely implantable biohybrid lung.

Objective

The research within this project aims at the development of an endothelialized oxygenator for the treatment of chronic lung disease. This promises a higher hemocompatibility and should allow for greatly enhanced long-term application. To achieve this goal, the research within the EndOxy project explores several strategies and designs in close cooperation with other research groups at the RWTH Aachen University.

Methods

In cooperation with the Leibniz Institute for Interactive Materials (DWI) and Department of Biohybrid & Medical Textiles (BioTex), the use of chemically functionalized membrane material is investigated for its efficiency to initialize and maintain a confluent cell layer. Mimicking the extracellular matrix, small signal peptides serve as ligands for endothelial cell receptors, thereby enhancing their binding to the surface.

BioTex investigates the cultivation process, and long-term stability and functionality of the endothelial cell layer. The cultivation of the cells is performed in bioreactor under dynamic conditions. The Department of Cardiovascular Engineering (CVE) design an up-scaled laboratory sample with an adequately sized gas exchange area. Therefore, the parameter set describing the flow conditions proven optimal experimentally in a bioreactor setup are investigated using computational fluid dynamics (CFD). Further, the fluid-mechanical characteristics are translated directly to the laboratory sample. Different technical designs are developed that allow a process chain incorporating all steps for the supply of a biohybrid lung such as pre-assembling, biofunctionalization, sterilization, assembly and cultivation. The different designs undergo in-vitro performance tests to compare the gas transfer capacity.

Cooperation Partners	Department of Biohybrid & Medical Textiles (BioTex) DWI - Leibniz Institute for Interactive Materials Department of Internal Medicine, Section of Pneumology Institut für Textiltechnik Aachen
Funding	Supported by a grant from the Interdisciplinary Centre for Clinical Research within the faculty of Medicine at the RWTH Aachen University (T12-2)