title: Phenotypic regulation of liver cells in a biofunctionalized three-dimensional hydrogel platform.
abstract: Loss of function is a major challenge for hepatocytes that are cultured on two-dimensional (2D) cell culture platforms. Biofunctionalized three-dimensional (3D) scaffolds produced by microfabrication strategies can overcome these limitations by presenting vital environmental cues, strong mechanical properties, and three-dimensional geometry to enable high-fidelity liver tissue engineering. Herein, we report the detailed investigation of hepatocarcinoma (Huh 7.5) cellular behavior in a collagen-functionalized microsphere-templated poly(ethylene glycol) (PEG) hydrogel scaffold which promotes 3D hepatic sheet morphology. Collagen conjugation led to improved liver-specific functions, including albumin production and cytochrome P450 (CYP450) activity. Importantly, the gene expression of numerous cell-adhesion markers was enhanced along with stimulated innate hepatocyte fibronectin production. Taken together, the findings reveal a close connection between hepatic cell morphology and gene expression, offering evidence that surface-coated collagen in the 3D hydrogel platform triggers the upregulation of hepatocyte-specific transcription factors and the secretion of liver metabolic markers.
authors.affiliation: School of Materials Science and Engineering, Nanyang Technological University, 50 Nanyang Avenue 639798, Singapore. njcho@e.ntu.edu.sg.
authors.forename: Myung Hee
authors.initials: MH
authors.lastname: Kim
authors.forename: Supriya K
authors.initials: SK
authors.lastname: Kumar
authors.forename: Hitomi
authors.initials: H
authors.lastname: Shirahama
authors.forename: Jeongeun
authors.initials: J
authors.lastname: Seo
authors.forename: Jae Ho
authors.initials: JH
authors.lastname: Lee
authors.forename: Nam-Joon
authors.initials: NJ
authors.lastname: Cho
mesh_terms: D000179:Acrylates / Q000737:chemistry; D000418:Albumins / Q000737:chemistry; D002448:Cell Adhesion; D018929:Cell Culture Techniques; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002470:Cell Survival; D003094:Collagen / Q000737:chemistry; D003102:Colloids; D003577:Cytochrome P-450 Enzyme System / Q000737:chemistry; D005353:Fibronectins / Q000737:chemistry; D022781:Hepatocytes / Q000166:cytology*; D006801:Humans; D020100:Hydrogels / Q000737:chemistry*; D021621:Imaging, Three-Dimensional; D008099:Liver / Q000166:cytology*; D008863:Microspheres; D010641:Phenotype; D011092:Polyethylene Glycols / Q000737:chemistry; D011137:Polystyrenes / Q000737:chemistry; D016062:Porosity; D013314:Stress, Mechanical; D023822:Tissue Engineering / Q000379:methods; D054457:Tissue Scaffolds
chemical_list: D000179:Acrylates; D000418:Albumins; D003102:Colloids; D005353:Fibronectins; D020100:Hydrogels; D011137:Polystyrenes; D011092:Polyethylene Glycols; D003094:Collagen; D003577:Cytochrome P-450 Enzyme System