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Engineered Fibrillar Fibronectin Networks as Three-Dimensional Tissue Scaffolds.


ABSTRACT: Extracellular matrix (ECM) proteins, and most prominently, fibronectin (Fn), are routinely used in the form of adsorbed pre-coatings in an attempt to create a cell-supporting environment in both two- and three-dimensional cell culture systems. However, these protein coatings are typically deposited in a form which is structurally and functionally distinct from the ECM-constituting fibrillar protein networks naturally deposited by cells. Here, the cell-free and scalable synthesis of freely suspended and mechanically robust three-dimensional (3D) networks of fibrillar fibronectin (fFn) supported by tessellated polymer scaffolds is reported. Hydrodynamically induced Fn fibrillogenesis at the three-phase contact line between air, an Fn solution, and a tessellated scaffold microstructure yields extended protein networks. Importantly, engineered fFn networks promote cell invasion and proliferation, enable in vitro expansion of primary cancer cells, and induce an epithelial-to-mesenchymal transition in cancer cells. Engineered fFn networks support the formation of multicellular cancer structures cells from plural effusions of cancer patients. With further work, engineered fFn networks can have a transformative impact on fundamental cell studies, precision medicine, pharmaceutical testing, and pre-clinical diagnostics.

SUBMITTER: Jordahl S 

PROVIDER: S-EPMC6851443 | biostudies-literature | 2019 Nov

REPOSITORIES: biostudies-literature

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Engineered Fibrillar Fibronectin Networks as Three-Dimensional Tissue Scaffolds.

Jordahl Stacy S   Solorio Luis L   Neale Dylan B DB   McDermott Sean S   Jordahl Jacob H JH   Fox Alexandra A   Dunlay Christopher C   Xiao Annie A   Brown Martha M   Wicha Max M   Luker Gary D GD   Lahann Joerg J  

Advanced materials (Deerfield Beach, Fla.) 20190930 46


Extracellular matrix (ECM) proteins, and most prominently, fibronectin (Fn), are routinely used in the form of adsorbed pre-coatings in an attempt to create a cell-supporting environment in both two- and three-dimensional cell culture systems. However, these protein coatings are typically deposited in a form which is structurally and functionally distinct from the ECM-constituting fibrillar protein networks naturally deposited by cells. Here, the cell-free and scalable synthesis of freely suspen  ...[more]

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