title: Long-term liver-specific functions of hepatocytes in electrospun chitosan nanofiber scaffolds coated with fibronectin.
abstract: In this study, a new 3D liver model was developed using biomimetic nanofiber scaffolds and co-culture system consisting of hepatocytes and fibroblasts for the maintenance of long-term liver functions. The chitosan nanofiber scaffolds were fabricated by the electrospinning technique. To enhance cellular adhesion and spreading, the surfaces of the chitosan scaffolds were coated with fibronectin (FN) by adsorption and evaluated for various cell types. Cellular phenotype, protein expression, and liver-specific functions were extensively characterized by immunofluorescent and histochemical stainings, albumin enzyme-linked immunosorbent assay and Cytochrome p450 detoxification assays, and scanning electron microscopy. The electrospun chitosan scaffolds exhibited a highly porous and randomly oriented nanofibrous structure. The FN coating on the surface of the chitosan nanofibers significantly enhanced cell attachment and spreading, as expected, as surface modification with this cell adhesion molecule on the chitosan surface is important for focal adhesion formation and integrin binding. Comparison of hepatocyte mono-cultures and co-cultures in 3D culture systems indicated that the hepatocytes in co-cultures formed colonies and maintained their morphologies and functions for prolonged periods of time. The 3D liver tissue model developed in this study will provide useful tools toward the development of engineered liver tissues for drug screening and tissue engineering applications. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 2119-2128, 2017.
authors.affiliation: Department of Biomedical Engineering, New Jersey Institute of Technology, Newark, New Jersey, 07102.
authors.forename: Divya
authors.initials: D
authors.lastname: Rajendran
authors.affiliation: Department of Biomedical Engineering, New Jersey Institute of Technology, Newark, New Jersey, 07102.
authors.forename: Ali
authors.initials: A
authors.lastname: Hussain
authors.affiliation: Department of Biomedical Engineering, New Jersey Institute of Technology, Newark, New Jersey, 07102.
authors.forename: Derek
authors.initials: D
authors.lastname: Yip
authors.affiliation: Department of Biomedical Engineering, New Jersey Institute of Technology, Newark, New Jersey, 07102.
authors.forename: Amit
authors.initials: A
authors.lastname: Parekh
authors.affiliation: Department of Biomedical Engineering, Rutgers University, Piscataway, New Jersey, 08854.
authors.forename: Anil
authors.initials: A
authors.lastname: Shrirao
authors.affiliation: Department of Biomedical Engineering, New Jersey Institute of Technology, Newark, New Jersey, 07102.
authors.forename: Cheul H
authors.initials: CH
authors.lastname: Cho
mesh_terms: D002448:Cell Adhesion; D048271:Chitosan / Q000737:chemistry*; D020099:Coated Materials, Biocompatible / Q000737:chemistry*; D018920:Coculture Techniques; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D005353:Fibronectins / Q000737:chemistry*; D056945:Hep G2 Cells; D022781:Hepatocytes / Q000166:cytology* / Q000378:metabolism; D006801:Humans; D057139:Nanofibers / Q000737:chemistry*; D054457:Tissue Scaffolds / Q000737:chemistry*
chemical_list: D020099:Coated Materials, Biocompatible; D005353:Fibronectins; D048271:Chitosan; D003577:Cytochrome P-450 Enzyme System
keywords: 3D liver model; electrospun chitosan nanofibers; hepatic co-culture; tissue engineering