4.3 Article

Biohybrid lung Development: Towards Complete Endothelialization of an Assembled Extracorporeal Membrane Oxygenator

Journal

BIOENGINEERING-BASEL
Volume 10, Issue 1, Pages -

Publisher

MDPI
DOI: 10.3390/bioengineering10010072

Keywords

biohybrid lung; ECMO; oxygenator; endothelialization; tissue engineering

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In order to establish a long-term lung-assist device for both bridge and destination therapy, a biohybrid lung (BHL) was developed based on contemporary extracorporeal membrane oxygenation (ECMO). The main challenge was to endothelialize all blood-contacting areas to overcome the drawbacks of ECMO. Through experimental testing, it was found that by adjusting cell seeding density and distribution, viable and confluent endothelial cell monolayers were successfully formed within 24 hours, even on different polymer surfaces.
Towards the establishment of a long-term lung-assist device to be used both as a bridge and as an alternative to lung transplantation according to final destination therapy, we develop the biohybrid lung (BHL) on the technical basis of contemporary extracorporeal membrane oxygenation (ECMO). Here, to overcome the significant drawbacks of ECMO, in particular the missing hemocompatibility of the artificial surfaces, all blood-contacting areas need to be endothelialized sufficiently. In continuation of our recent accomplishments, demonstrating the feasibility of establishing a physiological acting endothelial cell (EC) monolayer on the hollow fiber membranes (HFMs) of the ECMO in vitro, the next step towards BHL translation is the endothelialization of the complete oxygenator, consisting of HFMs and the surrounding housing. Therefore, we assessed EC seeding inside our model oxygenator (MOx), which simulated the conditions in the assembled HFM oxygenators in order to identify the most important factors influencing efficient endothelialization, such as cell seeding density, cell distribution, incubation time and culture medium consumption. Overall, upon adjusting the concentration of infused ECs to 15.2 x 10(4)/cm(2) and ensuring optimal dispersion of cells in the MOx, viable and confluent EC monolayers formed on all relevant surfaces within 24 h, even though they comprised different polymers, i.e., the fibronectin-coated HFMs and the polysulfone MOx housing. Periodic medium change ensured monolayer survival and negligible apoptosis rates comparable to the reference within the assembled system. By means of these results, revealing essential implications for BHL development, their clinical translation is coming one step closer to reality.

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