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

Authors :
Hussam Almesto Alabdullh
Michael Pflaum
Marisa Mälzer
Marcel Kipp
Hossein Naghilouy-Hidaji
Denise Adam
Christian Kühn
Russlan Natanov
Adelheid Niehaus
Axel Haverich
Bettina Wiegmann
Source :
Bioengineering, Vol 10, Iss 1, p 72 (2023)
Publication Year :
2023
Publisher :
MDPI AG, 2023.

Abstract

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 × 104/cm2 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.

Details

Language :
English
ISSN :
23065354
Volume :
10
Issue :
1
Database :
Directory of Open Access Journals
Journal :
Bioengineering
Publication Type :
Academic Journal
Accession number :
edsdoj.488a78c672ba4a82bcdbf74f6462c700
Document Type :
article
Full Text :
https://doi.org/10.3390/bioengineering10010072