Although state-of-the-art treatments of respiratory failure clearly have made some progress in terms of survival in patients suffering from severe respiratory system disorders, such as acute respiratory distress syndrome (ARDS), they failed to significantly improve the quality of life in patients with acute or chronic lung failure, including severe acute exacerbations of chronic obstructive pulmonary disease or ARDS as well. Limitations of standard treatment modalities, which largely rely on conventional mechanical ventilation, emphasize the urgent, unmet clinical need for developing novel (bio)artificial respiratory assist devices that provide extracorporeal gas exchange with a focus on direct extracorporeal CO2 removal from the blood. In this review, we discuss some of the novel concepts and critical prerequisites for such respiratory lung assist devices that can be used with an adequate safety profile, in the intensive care setting, as well as for long-term domiciliary therapy in patients with chronic ventilatory failure. Specifically, we describe some of the pivotal steps, such as device miniaturization, passivation of the blood-contacting surfaces by chemical surface modifications, or endothelial cell seeding, all of which are required for converting current lung assist devices into ambulatory lung assist device for long-term use in critically ill patients. Finally, we also discuss some of the risks and challenges for the long-term use of ambulatory miniaturized bioartificial lungs.
From *Xenios AG, Heilbronn, Germany
†Department of Interfacial Engineering and Materials Science, Fraunhofer Institute for Interfacial Engineering and Biotechnology (IGB), Stuttgart, Germany
‡Institut für Grenzflächenverfahrenstechnik und Plasmatechnologie (IGVP), University of Stuttgart, Stuttgart, Germany
§Reutlingen University, Reutlingen, Germany
¶Chemical Engineering Department, Imperial College, London, United Kingdom
‖Section of Respiratory Medicine, Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy
#Department Bioengineering, College of Engineering, Temple University, Philadelphia, Pennsylvania
**Temple Institute for Regenerative Medicine and Engineering, Temple University School of Medicine, Philadelphia, Pennsylvania.
Submitted for consideration June 2017; accepted for publication in revised form May 2018.
Disclosure: P.I. Lelkes was a paid consultant for Novalung. The other authors have no conflicts of interest to report.
The study was supported by grant from FP7-HEALTH-2012-INNOVATION-2 to the “AmbuLung Consortium: Ambulatory Bio-Artificial Lung,” Grant Agreement Number HEALTH-F4-2012-304932. This work is also supported by grants from the “Fraunhofer-Gesellschaft zur Förderung der angewandten Forschung e.V.” (K. Borchers, P.J. Kluger). P.I. Lelkes is the Laura H. Carnell Professor of Bioengineering and Chair, Department of Bioengineering, Temple University.
This paper is dedicated to the memory of Dame Professor Julia Polak, MD (1939–2014), who as a founding member of the AmbuLung Consortium was our all inspiration and spiritus rector, setting a perfect example for scientific integrity, vision, and admirable friendship.
Correspondence: Peter I. Lelkes, Department of Department of Bioengineering, Temple University, Engineering Building Room 811, 1947 N 12th Street, Philadelphia, PA 19122.Email: email@example.com.