EndoSpray

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picture of Lena Thiebes © Copyright: Felix Merkord

Name

Lena Thiebes

Research Group Leader Respiratory Tissue Engineering

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+49 241 80 47472

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EndoSpray – Efficient cell coating of biohybrid lungs by atomization of shear-stress resistant endothelial cells derived from induced pluripotent stem cells

Chronic lung disease is one of the most frequent causes of mortality in noncommunicable diseases worldwide with chronic obstructive pulmonary disease, COPD by short, representing the major share. Exacerbations in patients with severe COPD are often associated with acute respiratory failure with carbon dioxide retention requiring mechanical ventilation. If mechanical ventilation support fails, these patients have to be treated with extracorporeal carbon dioxide removal.

Complications associated to those extracorporeal lung support systems comprise inflammatory reactions, hemolysis, bleeding and thrombosis. Thus, its application requires continuous intensive care observation. Furthermore, unspecific protein adsorption to the membrane gradually reduces the efficacy of gas exchange. Both aspects are ascribed to the low hemo- and biocompatibility of the gas permeable membranes. Despite significant research activities, the core issue of limited hemocompatibility remains unresolved.

To overcome these issues, endothelialization of gas exchange membranes is suggested to form a natural non-thrombogenic surface and allow long-term use of such a biohybrid lung to finally enable implantation EndOxy. A lot of effort has already been taken on endothelialization of gas exchange membranes but without prove of upscaling feasibility, with sparse data on gas transfer and limited long-term success.

In this project, we evaluate endothelial cell production technologies and membrane seeding techniques for biohybrid lung development. Human induced pluripotent stem cell-derived endothelial cells, here hiPSC-ECs are used. Cell atomization or spraying CellSpray is considered an efficient and universal method to apply cells to various substrates. For seeding of endothelial cells, atomization is proposed to produce a uniform cell layer on gas exchange membranes. In this project, we will evaluate mid- and long-term behavior of hiPSC-ECs after atomization especially under dynamic culture.

With the described techniques, a proof of concept with long-term evaluation of an endothelialized laboratory oxygenator model will be accomplished in this project.

Partner

  • Dr. Ruth Olmer, Medizinische Hochschule Hannover

Funding:

  • German Research Foundation (DFG) within Priority Program “Towards an Implantable Lung” (Link: https://www.ukaachen.de/kliniken-institute/klinik-fuer-anaesthesiologie/forschung/spp-towards-an-implantable-lung)