Perfusion Cultivation of Artificial Liver ECM in Fibrous Polymer Sponges Biomimicking Scaffolds for Tissue Engineering

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Mader, Michael ; Helm, Moritz ; Lu, Mingxia ; Stenzel, Martina H. ; Jérôme, Valérie ; Agarwal, Seema ; Freitag, Ruth ; Greiner, Andreas:
Perfusion Cultivation of Artificial Liver ECM in Fibrous Polymer Sponges Biomimicking Scaffolds for Tissue Engineering.
In: Biomacromolecules. Bd. 21 (2020) Heft 10 . - S. 4094-4104.
ISSN 1526-4602
DOI: https://doi.org/10.1021/acs.biomac.0c00900

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Abstract

A major challenge in tissue enginerring and artificial scaffolding is to combine easy tunable scaffolds biomimicking the extracellular matrix of native organs, with delivery controlled cell culturing to create fully cellularized, large artificial 3D scaffolds. Aiming at bioartificial liver construction, we present our research using galactose functionalized, ultra-porous polylactide 3D nanofiber sponges fabricated out of electrospun fibers. Sponge biomodification by blend-galactosylation and in-solution coating is performed, respectively, using a PLA-galactose carrier-copolymer that is cell delivery promoting and features a pronounced autofluorescence. It allows to verify the galactosylation success, evaluate its quality and recording dye-free, high-resolution images of the sponge network using confocal laser scanning microscopy. The galactose-carrier and its impact on scaffold cellularization is validated in benchmark to several reference systems. Verification of the human hepatic cell asialo¬glycoprotein receptor presence and galactose interaction in culture is performed by Cu2+ receptor blocking experiments. The culture results are extensively investigated in- and ex-situ to trace and quantify the cell culture progress, cell activity and viability at different culture stages. Bioreactor cultivation of sponges reveal that the galactose-carrier does not only facilitate cell adhesion, but also enhances cellular distribution througout the scaffold. The promising 3D culture results allow us to move forward to create mature in-vitro liver-model research systems. The elaboration into ex-vivo testing platforms could help judging native cell material interactions with drugs or therapeutics, without the need of direct human or animal testing.