Development of a cell-seeded, bioartificial lung assist device

Introduction: COPD is the 4th leading cause of death worldwide. Extracorporeal lung assist devices that promote oxygenation and /or CO2 removal can improve lung protection and increase quality of life. As a drawback these systems limit patient mobility. In addition, long-term use of these devices is frequently accompanied by thromboembolic complications and device fouling due to inappropriate material properties of the blood contacting surfaces. Our goal is to develop the first wearable miniaturized lung assist device with improved hemocompatible surfaces. Methods: We designed prototypes of new, miniaturized hardware components with an optimized geometry to minimize hemolysis and thrombogenicity. To improve the hemocompatibility of the gas exchange membranes polymethlypentene (PMP), we seeded human dermal endothelial cells onto PMP hollow fibers, either coated with heparin/albumin, or following covalent functionalization with heparin/ REDV. Seeding efficiency and cell coverage were quantified microscopically. Results: We successfully miniaturized all hardware components and developed a new design of the gas exchanger, yielding improved blood distribution concomitant with adequate gas exchange in vitro and in vivo. Following seeding of stacked PMP fiber mats, the endothelial cells formed a confluent monolayer on the fibers, which was maintained for 5 days on the heparin/REDV coated fibers under both static and dynamic in vitro testing conditions in a novel perfusion bioreactor system. Conclusion: We successfully designed and implemented an advanced concept of a miniaturized wearable lung assist device, which is currently being tested in a porcine model. Future studies will test these devices in a first-in-man trial.