The Research Group Bioartificial Lung has moved to the Lower Saxony Centre for Biomedical Engineering, Implant Research and Development (NIFE) in March 2016.
Lung diseases account for 9 million deaths per year worldwide and rank third among causes of death in Europe. No adequate lung substitute is available and lung transplantation is currently the only possible treatment for lung failure. Because of this, the demand for donor organs has outgrown the supply. To overcome this shortage, our aim is to develop an implantable bio-hybrid lung which can replace a diseased or damaged lung.
The first stage of this work will be to improve an existing lung assistence system, the Novalung® iLA™ (interventional lung assist) Membrane Ventilator® (figure 1). This device includes several features which make it good starting point. Most important is that the microstructure of its gas exchange membrane mimics the alveolar-capillary bed of the human lung and flow resistance is sufficiently low that a normally beating heart is sufficient to move blood through the device for oxygenation. No additional mechanical pump is required.
The MHH was first to demonstrate that the Novalung® iLA™ could be used as a bridge to sustain patients with lung failure until they could receive a lung transplant. This work demonstrated that the gas exchange capacity of this iLA™ device was sufficient to fully replace lung function for a limited period of time.
The main drawback of the Novalung® iLA™ is that it fails in three to four weeks due to membrane clotting and neointima formation. Apparently, the surface of the gas exchange membrane triggers protein binding, blood cell aggregation and thrombus formation. We hope to improve the hemo-compatibility of the Novalung® iLA™ by seeding endothelial cells onto the membrane to give it a more natural endothelial surface (figure 2). This system will enable us to study the interactions between endothelial cells and artificial membranes. The endothelial cells will be characterized with respect to vitality, proliferation, cell adhesion, and immunological alterations at the molecular level using fluorescence microscopy and fluorescence activated cell sorting (FACS). Phenotypic changes at the level of gene expression will be investigated quantitatively with the reverse-transcription polymerase-chain-reaction (qRT-PCR). This information is a prerequisite for the further optimization of endothelial cell seeding conditions.
Primary endothelial cells are seeded on membrane (A). Cells forming a unified cell network comparable to the situation in a blood vessel. Thereby, the direct contact between blood and the artificial surface of the membrane is prevented (B). Modified membranes may be suitable for the permanent application in medical devices like the iLA™ Membrane Ventilator® (C).
In cooperation with our external collaborators (e.g. Laser Zentrum Hannover), we ultimately plan to modify the gas exchange membrane to make it more hemo-compatible using new materials and modified surface structure.