title: Basement Membrane Mimics of Biofunctionalized Nanofibers for a Bipolar-Cultured Human Primary Alveolar-Capillary Barrier Model.
abstract: In vitro reconstruction of an alveolar barrier for modeling normal lung functions and pathological events serve as reproducible, high-throughput pharmaceutical platforms for drug discovery, diagnosis, and regenerative medicine. Despite much effort, the reconstruction of organ-level alveolar barrier functions has failed due to the lack of structural similarity to the natural basement membrane, functionalization with specific ligands for alveolar cell function, the use of primary cells and biodegradability. Here we report a bipolar cultured alveolar-capillary barrier model of human primary cells supported by a basement membrane mimics of fully synthetic bifunctional nanofibers. One-step electrospinning process using a bioresorbable polyester and multifunctional star-shaped polyethylene glycols (sPEG) enables the fabrication of an ultrathin nanofiber mesh with interconnected pores. The nanofiber mesh possessed mechanical stability against cyclic expansion as seen in the lung in vivo. The sPEGs as an additive provide biofunctionality to fibers through the conjugation of peptide to the nanofibers and hydrophilization to prevent unspecific protein adsorption. Biofunctionalized nanofiber meshes facilitated bipolar cultivation of endothelial and epithelial cells with fundamental alveolar functionality and showed higher permeability for molecules compared to microporous films. This nanofiber mesh for a bipolar cultured barrier have the potential to promote growth of an organ-level barrier model for modeling pathological conditions and evaluating drug efficacy, environmental pollutants, and nanotoxicology.
authors.affiliation: DWI - Leibniz-Institute for Interactive Materials , Forckenbeckstrasse 50, D-52056, Aachen, Germany.
authors.forename: Akihiro
authors.identifier: 0000-0002-3160-6385
authors.initials: A
authors.lastname: Nishiguchi
authors.affiliation: DWI - Leibniz-Institute for Interactive Materials , Forckenbeckstrasse 50, D-52056, Aachen, Germany.
authors.forename: Smriti
authors.initials: S
authors.lastname: Singh
authors.affiliation: DWI - Leibniz-Institute for Interactive Materials , Forckenbeckstrasse 50, D-52056, Aachen, Germany.
authors.forename: Matthias
authors.initials: M
authors.lastname: Wessling
authors.affiliation: Institute of Pathology, University Medical Center, Johannes Gutenberg University , Langenbeckstrasse 1, D-55101, Mainz, Germany.
authors.forename: Charles J
authors.initials: CJ
authors.lastname: Kirkpatrick
authors.affiliation: DWI - Leibniz-Institute for Interactive Materials , Forckenbeckstrasse 50, D-52056, Aachen, Germany.|Institute of Technical and Macromolecular Chemistry, RWTH Aachen University , Worringerweg 2, 52074, Aachen, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Möller
mesh_terms: D001485:Basement Membrane / Q000737:chemistry*; D001672:Biocompatible Materials / Q000737:chemistry*; D002448:Cell Adhesion / Q000187:drug effects; D045744:Cell Line, Tumor; D042783:Endothelial Cells / Q000166:cytology; D061307:Human Umbilical Vein Endothelial Cells / Q000166:cytology; D006801:Humans; D057139:Nanofibers / Q000737:chemistry*; D010539:Permeability; D011091:Polyesters; D011092:Polyethylene Glycols / Q000737:chemistry; D023822:Tissue Engineering; D054457:Tissue Scaffolds / Q000737:chemistry*
chemical_list: D001672:Biocompatible Materials; D011091:Polyesters; D011092:Polyethylene Glycols