title: Robust bioengineered 3D functional human intestinal epithelium.
abstract: Intestinal functions are central to human physiology, health and disease. Options to study these functions with direct relevance to the human condition remain severely limited when using conventional cell cultures, microfluidic systems, organoids, animal surrogates or human studies. To replicate in vitro the tissue architecture and microenvironments of native intestine, we developed a 3D porous protein scaffolding system, containing a geometrically-engineered hollow lumen, with adaptability to both large and small intestines. These intestinal tissues demonstrated representative human responses by permitting continuous accumulation of mucous secretions on the epithelial surface, establishing low oxygen tension in the lumen, and interacting with gut-colonizing bacteria. The newly developed 3D intestine model enabled months-long sustained access to these intestinal functions in vitro, readily integrable with a multitude of different organ mimics and will therefore ensure a reliable ex vivo tissue system for studies in a broad context of human intestinal diseases and treatments.
authors.affiliation: Department of Biomedical Engineering, Tufts University, 4 Colby Street, Medford, MA 02155, USA.
authors.forename: Ying
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Department of Biomedical Engineering, Tufts University, 4 Colby Street, Medford, MA 02155, USA.
authors.forename: Yinan
authors.initials: Y
authors.lastname: Lin
authors.affiliation: Department of Molecular Biology and Microbiology, Tufts University School of Medicine, 145 Harrison Ave, Boston, MA 02111, USA.
authors.forename: Kimberly M
authors.initials: KM
authors.lastname: Davis
authors.affiliation: Department of Biomedical Engineering, Tufts University, 4 Colby Street, Medford, MA 02155, USA.
authors.forename: Qianrui
authors.initials: Q
authors.lastname: Wang
authors.affiliation: Department of Biomedical Engineering, Tufts University, 4 Colby Street, Medford, MA 02155, USA.|Graduate School of Biomedical Engineering, UNSW Australia, Sydney, NSW, Australia.
authors.forename: Jelena
authors.initials: J
authors.lastname: Rnjak-Kovacina
authors.affiliation: Department of Biomedical Engineering, Tufts University, 4 Colby Street, Medford, MA 02155, USA.
authors.forename: Chunmei
authors.initials: C
authors.lastname: Li
authors.affiliation: Department of Molecular Biology and Microbiology, Tufts University School of Medicine, 145 Harrison Ave, Boston, MA 02111, USA.
authors.forename: Ralph R
authors.initials: RR
authors.lastname: Isberg
authors.affiliation: Department of Molecular Biology and Microbiology, Tufts University School of Medicine, 145 Harrison Ave, Boston, MA 02111, USA.
authors.forename: Carol A
authors.initials: CA
authors.lastname: Kumamoto
authors.affiliation: Department of Molecular Biology and Microbiology, Tufts University School of Medicine, 145 Harrison Ave, Boston, MA 02111, USA.
authors.forename: Joan
authors.initials: J
authors.lastname: Mecsas
authors.affiliation: Department of Biomedical Engineering, Tufts University, 4 Colby Street, Medford, MA 02155, USA.
authors.forename: David L
authors.initials: DL
authors.lastname: Kaplan
mesh_terms: D000818:Animals; D015374:Biosensing Techniques; D002460:Cell Line; D004847:Epithelial Cells / Q000378:metabolism; D006801:Humans; D019476:Insect Proteins; D007413:Intestinal Mucosa / Q000378:metabolism; D009940:Organoids; D010100:Oxygen / Q000378:metabolism; D047011:Silk; D046509:Tissue Culture Techniques; D023822:Tissue Engineering; D054457:Tissue Scaffolds
chemical_list: D019476:Insect Proteins; D047011:Silk; D010100:Oxygen