title: Soft Hydrogels Featuring In-Depth Surface Density Gradients for the Simple Establishment of 3D Tissue Models for Screening Applications.
abstract: Three-dimensional (3D) cell culture models are gaining increasing interest for use in drug development pipelines due to their closer resemblance to human tissues. Hydrogels are the first-choice class of materials to recreate in vitro the 3D extra-cellular matrix (ECM) environment, important in studying cell-ECM interactions and 3D cellular organization and leading to physiologically relevant in vitro tissue models. Here we propose a novel hydrogel platform consisting of a 96-well plate containing pre-cast synthetic PEG-based hydrogels for the simple establishment of 3D (co-)culture systems without the need for the standard encapsulation method. The in-depth density gradient at the surface of the hydrogel promotes the infiltration of cells deposited on top of it. The ability to decouple hydrogel production and cell seeding is intended to simplify the use of hydrogel-based platforms and thus increase their accessibility. Using this platform, we established 3D cultures relevant for studying stem cell differentiation, angiogenesis, and neural and cancer models.
authors.affiliation: 1 Laboratory of Biosensors and Bioelectronics, University and ETH Zurich, Zurich, Switzerland.|2 State Key Laboratory of Bioelectronics, School of Biological Science and Medical Engineering, Southeast University, Nanjing, China.
authors.forename: Ning
authors.initials: N
authors.lastname: Zhang
authors.affiliation: 3 Laboratory for Cell and Tissue Engineering, Department of Obstetrics, University Hospital Zurich, Zurich, Switzerland.|4 Ectica Technologies AG, Zurich, Switzerland.
authors.forename: Vincent
authors.initials: V
authors.lastname: Milleret
authors.affiliation: 1 Laboratory of Biosensors and Bioelectronics, University and ETH Zurich, Zurich, Switzerland.
authors.forename: Greta
authors.initials: G
authors.lastname: Thompson-Steckel
authors.affiliation: 2 State Key Laboratory of Bioelectronics, School of Biological Science and Medical Engineering, Southeast University, Nanjing, China.
authors.forename: Ning-Ping
authors.initials: NP
authors.lastname: Huang
authors.affiliation: 1 Laboratory of Biosensors and Bioelectronics, University and ETH Zurich, Zurich, Switzerland.
authors.forename: János
authors.initials: J
authors.lastname: Vörös
authors.affiliation: 4 Ectica Technologies AG, Zurich, Switzerland.
authors.forename: Benjamin R
authors.initials: BR
authors.lastname: Simona
authors.affiliation: 3 Laboratory for Cell and Tissue Engineering, Department of Obstetrics, University Hospital Zurich, Zurich, Switzerland.
authors.forename: Martin
authors.initials: M
authors.lastname: Ehrbar
mesh_terms: D018929:Cell Culture Techniques / Q000379:methods*; D002454:Cell Differentiation / Q000187:drug effects; D045744:Cell Line, Tumor; D005109:Extracellular Matrix / Q000187:drug effects; D006801:Humans; D020100:Hydrogels / Q000737:chemistry*; D009389:Neovascularization, Pathologic / Q000473:pathology
chemical_list: D020100:Hydrogels
keywords: 3D cell culture; automation; gradient; hydrogel; screening; sequential seeding; tissue model