Biohybrid Lung


Lung disease rank third among the causes of death worldwide. Currently, lung transplantation remains the only therapeutic option to treat lung failure, since there are no long-term alternatives. However, lung transplantation is limited by the low availability of donor organs. The work conducted by the Bioartificial Lung group aims at overcoming the limited availability of donor lungs, by developing an implantable biohybrid lung, which can provide a long-term solution of fully restoring lung function.

Research Focus

A medical device as short-term bridge to transplantation

The MHH was successfully demonstrating that an artificial medical device, the Novalung® iLA™ (interventional lung assist) Membrane Ventilator® (figure 1) could be applied as a bridge to sustain patients with lung failure until they can receive a suitable lung transplant. This study revealed that the device provides adequate gas exchange probabilities to fully replace lung function by effectively replenishing oxygen and removing carbon dioxide from the patients’ blood utilising gas exchanging membranes. Moreover, the resistance to blood flow generated by the device was sufficiently low to allow a healthy beating heart to pump blood through the oxygenation device unassisted.

Figure 1.

Figure 1. The iLA™ (interventional lung assist) from Novalung®

Optimising the device for long term application and implantation

However, the haemocompatibility of the blood-contacting surfaces of the oxygenation device is limited. Owing to this, the application of the device is restricted to only a short period of time, since within three to four weeks it tends to fail due to the membrane clotting and neointima formation. Aiming at an improved haemocompatibility of the device components, especially of the gas exchanging membranes, the strategy of the Biohybrid Lung group is to seed the blood contacting surfaces of the components with endothelial cells (figure 2). Thereby the focus of work is to investigate and optimise the interaction between endothelial cells and the artificial device parts.



Figure 2.

Figure 2. Schematic of the gas-exchange membrane seeding. (A) Primary endothelial cells seeded on the membrane. (B) Cells form an intact monolayer comparable to that of blood vessels. The endothelial monolayer prevents direct contact of the blood with the artificial membrane. (C) Modified membranes may be suitable for permanent application in medical devices like the iLA™ Membrane Ventilator®.


Based on the knowledge obtained in cooperation with our external collaborators (e.g. Organic Chemistry from University Hannover, Laser Centre Hannover), the work focuses on modifying the properties (e.g. surface structure, surface coating) of the device materials, with a view to achieving optimal cell adhesion and, consequently, long-term haemocompatibility. Once the long-term haemocompatibility of the device has been optimised, further work will focus on generating a fully implantable biohybrid lung, though optimising the shape and size of the device, including the cannulas and cannulation techniques. These will allow the riskless mobilisation of the patients while being on oxygenation support.


  • Dr. G. Dräger, Leibniz University of Hannover, Institute of Organic Chemistry, Unit 7.1 Functional Polymers and Regenerative Agents
  • Prof. Dr. Scheper, Leibniz University, Institute for Technical Chemistry, Unit 10.1 Production and Purification of Recombinant Proteins
  • Prof. Dr. Glasmacher, Prof. Dr. Wolkers, Leibniz University of Hannover, Unit 10.3 Biostabiliszation of Tissue and Macromolecular Assemblies
  • Novalung GmbH, Heilbronn
  • MHH Institute for Transfusion Medicine (Blasczyk), Hannover Medical School
  • Dr. C Kühn, Crossbit Hannover,
  • Prof. Dr. M. Ulrich, Hannover Medical School, Leibniz Laboratories for Biotechnology and Artificial Organs, Unit 4.2 Lung Regeneration and Repair
  • Dr. R. Olmer, Hannover Medical School, Leibniz Laboratories for Biotechnology and Artificial Organs, German Center for Lung Research, BREATH ELD 3.1
  • Prof. Dr. J. Schein, University of Federal Armed Forces Munich, Institute for Plasmatechnology and Mathematics,
  • Prof. Dr. C.S. von Kaisenberg, Clinic for Gynaecology and Obstetrics, Hannover Medical School, Leibniz Laboratories for Biotechnology and Artificial Organs
  • Prof. Dr. S. Barcikowski, University of Duisburg-Essen, Technical Chemistry I,


  • Dr. Michael Pflaum was awarded 3rd prize in the VisiSens Competition (2012), Presens GmbH, Regensburg
  • Bettina Wiegmann was awarded the: ASAIO Y. NOSÈ INTERNATIONAL FELLOWSHIP, “Endothelialization of a Poly-Methyl-Pentene Gas-Exchange Membrane”, Y. NOSÉ FELLOWSHIP FUND (55th Annual ASAIO Conference 2009, Dallas)
  • Dr. C. Hess: Research Award of the German Society for Thoracic Surgery (DGT) Title of the work: ‘Endothelialisierung von Poly-4-Methyl-1-Pentene (PMP) Gasaustauschmembranen in künstlichen Lungensystemen’ awarded at the 17. Annual Meeting of the German Society for Thoracic Surgery, 11-13 September 2008, Bremen


2013 - ongoing


De A, Pflaum M, Wirth D, Sedding D, Wiegmann B, Haverich A, Korossis S. Metabolic Assessment of Therapies for the Development of Drug-Eluting Stents. Tissue Engineering Part A. 2017. 23:S96-S96

Ricklefs M, Korossis S, Haverich A, Schilling T. Polymeric Scaffolds for Bioartificial Cardiovascular Prostheses. In: Scaffolds in Tissue Engineering-Materials, Technologies and Clinical Applications. Edited by: Francesco Baino. InTech, Croatia 2017.

Fidalgo C, Iop L, Sciro M, Harder M, Mavrilas D, Korossis S, Bagno A, Palù G, Aguiari P, Gerosa G. A Sterilization Method for Decellularized Xenogeneic Cardiovascular Scaffolds. Acta Biomaterialia.

Schumer E, Höffler K, Kuehn C, Slaughter M, Haverich A, Wiegmann B. In-vitro evaluation of limitations and possibilities for the future use of intracorporeal gas exchangers placed in the upper lobe position. Journal of Artificial Organs. 2017.

Granados M, Morticelli L, Andriopoulou S, Kalozoumis P, Pflaum M, Iablonskii P, Glasmacher B, Harder M, Hegermann J, Wrede C, Tudorache I, Cebotari S, Hilfiker A, Haverich A, Korossis S. Development and Characterization of a Porcine Mitral Valve Scaffold for Tissue Engineering. J Cardiovasc Transl Res. 2017/05/04 ed2017. p. 374-90.

Pflaum M, Kühn-Kauffeldt M, Schmeckebier S, Dipresa D, Chauhan K, Wiegmann B, Haug RJ, Schein J, Haverich A, Korossis S. Endothelialization and characterization of titanium dioxide-coated gas-exchange membranes for application in the bioartificial lung. Acta biomaterialia. 2017;50:510-21.


Wiegmann B, von Seggern H, Hoffler K, Korossis S, Dipresa D, Pflaum M, Schmeckebier S, Seume J, Haverich A. Developing a biohybrid lung - sufficient endothelialization of poly-4-methly-1-pentene gas exchange hollow-fiber membranes. J Mech Behav Biomed Mater. 2016;60:301-11.

Theodoridis K, Muller J, Ramm R, Findeisen K, Andree B, Korossis S, Haverich A, Hilfiker A. Effects of combined cryopreservation and decellularization on the biomechanical, structural and biochemical properties of porcine pulmonary heart valves. Acta biomaterialia. 2016;43:71-7.

Roberts N, Morticelli L, Jin Z, Ingham E, Korossis S. Regional biomechanical and histological characterization of the mitral valve apparatus: Implications for mitral repair strategies. J Biomech. 2016;49(12):2491-501.

Marino M, Korossis S. Cardiovascular biomechanics in health and disease. Journal of Biomechanics. 2016;49(12):2319-20.

Joda A, Jin Z, Haverich A, Summers J, Korossis S. Multiphysics simulation of the effect of leaflet thickness inhomogeneity and material anisotropy on the stress-strain distribution on the aortic valve. J Biomech. 2016;49(12):2502-12.


Alexandros R, Wolkers WF, Oleksandr G, Panagiotis K, Marc M, Holger Z, Sotirios K, Birgit G. - Coaxial Electrospinning as a Process to Engineer Biodegradable Polymeric. 2015

Katsimpoulas M, Morticelli L, Michalopoulos E, Gontika I, Stavropoulos-Giokas C, Kostakis A, Haverich A, Korossis S. Investigation of the Biomechanical Integrity of Decellularized Rat Abdominal Aorta. Transplant Proc. 2015;47(4):1228-33.

Paniagua Gutierrez JR, Berry H, Korossis S, Mirsadraee S, Lopes SV, da Costa F, Kearney J, Watterson K, Fisher J, Ingham E. Regenerative Potential of Low-Concentration Sds-Decellularized Porcine Aortic Valved Conduits in Vivo. Tissue Eng Part A. 2015;21(1-2):332-42.

Wiegmann B, Korossis S, Burgwitz K, Hurschler C, Fischer S, Haverich A, Kuehn C. In Vitro Comparison of Biological and Synthetic Materials for Skeletal Chest Wall Reconstruction. Ann Thorac Surg. 2015;99(3):991-8.

Sommer W, Marsch G, Kaufeld T, Rontgen P, Beutel G, Tongers J, Warnecke G, Tudorache I, Schieffer B, Haverich A, Kuhn C. Cardiac Awake Extracorporeal Life Support-Bridge to Decision? Artif Organs. 2015;39(5):400-8.

Tudorache I, Sommer W, Kuhn C, Wiesner O, Hadem J, Fuhner T, Ius F, Avsar M, Schwerk N, Bothig D, Gottlieb J, Welte T, Bara C, Haverich A, Hoeper MM, Warnecke G. Lung Transplantation for Severe Pulmonary Hypertension--Awake Extracorporeal Membrane Oxygenation for Postoperative Left Ventricular Remodelling. Transplantation. 2015;99(2):451-8.

Iablonskii P, Cebotari S, Tudorache I, Granados M, Morticelli L, Goecke T, Klein N, Korossis S, Hilfiker A, Haverich A. Tissue-Engineered Mitral Valve: Morphology and Biomechanics Dagger. Interact Cardiovasc Thorac Surg. 2015;20(6):712-9; discussion 9.

Ius F, Sommer W, Tudorache I, Avsar M, Siemeni T, Salman J, Puntigam J, Optenhoefel J, Greer M, Welte T, Wiesner O, Haverich A, Hoeper M, Kuehn C, Warnecke G. Veno-Veno-Arterial Extracorporeal Membrane Oxygenation for Respiratory Failure with Severe Haemodynamic Impairment: Technique and Early Outcomes. Interact Cardiovasc Thorac Surg. 2015;20(6):761-7.

Mohrmann C, Herold C, Pflaum M, Kramer R, Vogt PM, Allert S. [Viability and Particle Size of Fat Grafts Obtained with Wal and Pal Techniques]. Handchir Mikrochir Plast Chir. 2015;47(4):246-52. Epub 2015/08/20. Vitalitat und Partikelgrosse bei der autologen Fetttransplantation mit der WAL und der PAL Technik.


Wiegmann B, Figueiredo C, Gras C, Pflaum M, Schmeckebier S, Korossis S, Haverich A, Blasczyk R. Prevention of Rejection of Allogeneic Endothelial Cells in a Biohybrid Lung by Silencing Hla-Class I Expression. Biomaterials. 2014;35(28):8123-33.

Luo J, Korossis SA, Wilshaw SP, Jennings LM, Fisher J, Ingham E. Development and Characterization of Acellular Porcine Pulmonary Valve Scaffolds for Tissue Engineering. Tissue Eng Part A. 2014;20(21-22):2963-74.

Hess C, Schwenke A, Wagener P, Franzka S, Laszlo Sajti C, Pflaum M, Wiegmann B, Haverich A, Barcikowski S. Dose-Dependent Surface Endothelialization and Biocompatibility of Polyurethane Noble Metal Nanocomposites. J Biomed Mater Res A. 2014;102(6):1909-20.


Wiegmann B, Maurer A, Zhang R, Zardo P, Haverich A, Fischer S. Combined Pulmonary and Renal Support in a Single Extracorporeal Device. ASAIO J. 2013;59(4):433-8.

Morticelli L, Thomas D, Roberts N, Ingham E, Korossis S. Investigation of the Suitability of Decellularized Porcine Pericardium in Mitral Valve Reconstruction. J Heart Valve Dis. 2013;22(3):340-53. Epub 2013/10/25.

Riches K, Angelini TG, Mudhar GS, Kaye J, Clark E, Bailey MA, Sohrabi S, Korossis S, Walker PG, Scott DJ, Porter KE. Exploring Smooth Muscle Phenotype and Function in a Bioreactor Model of Abdominal Aortic Aneurysm. J Transl Med. 2013;11:208.

Hoeper MM, Wiesner O, Hadem J, Wahl O, Suhling H, Duesberg C, Sommer W, Warnecke G, Greer M, Boenisch O, Busch M, Kielstein JT, Schneider A, Haverich A, Welte T, Kuhn C. Extracorporeal Membrane Oxygenation Instead of Invasive Mechanical Ventilation in Patients with Acute Respiratory Distress Syndrome. Intensive Care Med. 2013;39(11):2056-7.

Moller L, Hess C, Palecek J, Su Y, Haverich A, Kirschning A, Drager G. Towards a Biocompatible Artificial Lung: Covalent Functionalization of Poly(4-Methylpent-1-Ene) (Tpx) with Crgd Pentapeptide. Beilstein J Org Chem. 2013;9:270-7.

2006 - 2012


Kauffeldt M, Pflaum M, Pietzka M, Wiegmann B, Schein J, Haverich A. Triggerless pulsed vacuum arc plasma deposition of thin TiO2 coatings on Polymethylpenten foils as a functional coating for medical applications. Discharges and Electrical Insulation in Vacuum (ISDEIV). accepted for publication. 2012.

Beisswenger C, Hess C, Bals R. Aspergillus Fumigatus Conidia Induce Interferon-Beta Signalling in Respiratory Epithelial Cells. Eur Respir J. 2012;39(2):411-8.

Warnecke G, Moradiellos J, Tudorache I, Kuhn C, Avsar M, Wiegmann B, Sommer W, Ius F, Kunze C, Gottlieb J, Varela A, Haverich A. Normothermic Perfusion of Donor Lungs for Preservation and Assessment with the Organ Care System Lung before Bilateral Transplantation: A Pilot Study of 12 Patients. Lancet. 2012;380(9856):1851-8.

Michalopoulos E, Knight RL, Korossis S, Kearney JN, Fisher J, Ingham E. Development of Methods for Studying the Differentiation of Human Mesenchymal Stem Cells under Cyclic Compressive Strain. Tissue Eng Part C Methods. 2012;18(4):252-62.

Zhang R, Mietchen C, Kruger M, Wiegmann B, Golpon H, Dettmer S, Haverich A, Zardo P. Endobronchial Ultrasound Guided Fine Needle Aspiration Versus Transcervical Mediastinoscopy in Nodal Staging of Non Small Cell Lung Cancer: A Prospective Comparison Study. J Cardiothorac Surg. 2012;7:51.

Ius F, Kuehn C, Tudorache I, Sommer W, Avsar M, Boethig D, Fuehner T, Gottlieb J, Hoeper M, Haverich A, Warnecke G. Lung Transplantation on Cardiopulmonary Support: Venoarterial Extracorporeal Membrane Oxygenation Outperformed Cardiopulmonary Bypass. J Thorac Cardiovasc Surg. 2012;144(6):1510-6.

Fuehner T, Kuehn C, Hadem J, Wiesner O, Gottlieb J, Tudorache I, Olsson KM, Greer M, Sommer W, Welte T, Haverich A, Hoeper MM, Warnecke G. Extracorporeal Membrane Oxygenation in Awake Patients as Bridge to Lung Transplantation. Am J Respir Crit Care Med. 2012;185(7):763-8. Epub 2012/01/24.

Zhang R, Wiegmann B, Fischer S, Dickgreber NJ, Hagl C, Kruger M, Haverich A, Zardo P. Simultaneous Cardiac and Lung Surgery for Incidental Solitary Pulmonary Nodule: Learning from the Past. Thorac Cardiovasc Surg. 2012;60(2):150-5.

Olmer R, Lange A, Selzer S, Kasper C, Haverich A, Martin U, Zweigerdt R. Suspension Culture of Human Pluripotent Stem Cells in Controlled, Stirred Bioreactors. Tissue Eng Part C Methods. 2012;18(10):772-84.


Zardo P, Zhang R, Wiegmann B, Haverich A, Fischer S. Biological Materials for Diaphragmatic Repair: Initial Experiences with the Periguard Repair Patch(R). Thorac Cardiovasc Surg. 2011;59(1):40-4.

Kuhn C, Disque C, Muhl H, Orszag P, Stiesch M, Haverich A. Evaluation of Commercial Universal Rrna Gene Pcr Plus Sequencing Tests for Identification of Bacteria and Fungi Associated with Infectious Endocarditis. J Clin Microbiol. 2011;49(8):2919-23.

Gruene M, Pflaum M, Deiwick A, Koch L, Schlie S, Unger C, Wilhelmi M, Haverich A, Chichkov BN. Adipogenic Differentiation of Laser-Printed 3d Tissue Grafts Consisting of Human Adipose-Derived Stem Cells. Biofabrication. 2011;3(1):015005.

Gruene M, Pflaum M, Hess C, Diamantouros S, Schlie S, Deiwick A, Koch L, Wilhelmi M, Jockenhoevel S, Haverich A, Chichkov B. Laser Printing of Three-Dimensional Multicellular Arrays for Studies of Cell-Cell and Cell-Environment Interactions. Tissue Eng Part C Methods. 2011;17(10):973-82.

Bisdas T, Beutel G, Warnecke G, Hoeper MM, Kuehn C, Haverich A, Teebken OE. Vascular Complications in Patients Undergoing Femoral Cannulation for Extracorporeal Membrane Oxygenation Support. Ann Thorac Surg. 2011;92(2):626-31.

Martens A, Gruh I, Dimitroulis D, Rojas SV, Schmidt-Richter I, Rathert C, Khaladj N, Gawol A, Chikobava MG, Martin U, Haverich A, Kutschka I. Rhesus Monkey Cardiosphere-Derived Cells for Myocardial Restoration. Cytotherapy. 2011;13(7):864-72.

Zweigerdt R, Olmer R, Singh H, Haverich A, Martin U. Scalable Expansion of Human Pluripotent Stem Cells in Suspension Culture. Nat Protoc. 2011;6(5):689-700.

Beutel G, Wiesner O, Eder M, Hafer C, Schneider AS, Kielstein JT, Kühn C, Heim A, Ganzenmüller T, Kreipe H-H, Haverich A, Tecklenburg A, Ganser A, Welte T, Hoeper MM. Virus-Associated Hemophagocytic Syndrome as a Major Contributor to Death in Patients with 2009 Influenza a (H1n1) Infection. Critical Care. 2011;15(2):R80-R.


Hess C, Herr C, Beisswenger C, Zakharkina T, Schmid RM, Bals R. Myeloid Rela Regulates Pulmonary Host Defense Networks. Eur Respir J. 2010;35(2):343-52.

Hess C, Wiegmann B, Maurer AN, Fischer P, Moller L, Martin U, Hilfiker A, Haverich A, Fischer S. Reduced Thrombocyte Adhesion to Endothelialized Poly 4-Methyl-1-Pentene Gas Exchange Membranes-a First Step toward Bioartificial Lung Development. Tissue Eng Part A. 2010;16(10):3043-53.

Olsson KM, Simon A, Strueber M, Hadem J, Wiesner O, Gottlieb J, Fuehner T, Fischer S, Warnecke G, Kuhn C, Haverich A, Welte T, Hoeper MM. Extracorporeal Membrane Oxygenation in Nonintubated Patients as Bridge to Lung Transplantation. Am J Transplant. 2010;10(9):2173-8. Epub 2010/07/20.


Meyer A, Struber M, Fischer S. Advances in Extracorporeal Ventilation. Anesthesiol Clin. 2008;26(2):381-91, viii.

Fischer S, Hoeper MM, Bein T, Simon AR, Gottlieb J, Wisser W, Frey L, Van Raemdonck D, Welte T, Haverich A, Strueber M. Interventional Lung Assist: A New Concept of Protective Ventilation in Bridge to Lung Transplantation. ASAIO J. 2008;54(1):3-10. Epub 2008/01/22.


Fischer S, Bohn D, Rycus P, Pierre AF, de Perrot M, Waddell TK, Keshavjee S. Extracorporeal Membrane Oxygenation for Primary Graft Dysfunction after Lung Transplantation: Analysis of the Extracorporeal Life Support Organization (Elso) Registry. J Heart Lung Transplant. 2007;26(5):472-7.

Fischer S, Hoeper MM, Tomaszek S, Simon A, Gottlieb J, Welte T, Haverich A, Strueber M. Bridge to Lung Transplantation with the Extracorporeal Membrane Ventilator Novalung in the Veno-Venous Mode: The Initial Hannover Experience. ASAIO J. 2007;53(2):168-70.


Fischer S, Simon AR, Welte T, Hoeper MM, Meyer A, Tessmann R, Gohrbandt B, Gottlieb J, Haverich A, Strueber M. Bridge to lung transplantation with the novel pumpless interventional lung assist device NovaLung. J Thorac Cardiovasc Surg. 2006;131(3):719-23. Epub 2006/03/07.

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