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A 3D tension bioreactor platform to study the interplay between ECM stiffness and tumor phenotype

Paper ID Volume ID Publish Year Pages File Format Full-Text
22983 43408 2015 4 PDF Available
Title
A 3D tension bioreactor platform to study the interplay between ECM stiffness and tumor phenotype
Abstract

•We detail the design and implementation of a Col I hydrogel tension bioreactor.•This system allows hydrogel stiffening without changing ECM structure.•Tumor cells invade into the Col I hydrogels with increased stiffness.•We can adapt our system to create 3D gradients of ECM stiffness.•Stiffness gradients direct tumor cell invasion.

Extracellular matrix (ECM) structure, composition, and stiffness have profound effects on tissue development and pathologies such as cardiovascular disease and cancer. Accordingly, a variety of synthetic hydrogel systems have been designed to study the impact of ECM composition, density, mechanics, and topography on cell and tissue phenotype. However, these synthetic systems fail to accurately recapitulate the biological properties and structure of the native tissue ECM. Natural three dimensional (3D) ECM hydrogels, such as collagen or hyaluronic acid, feature many of the chemical and physical properties of tissue, yet, these systems have limitations including the inability to independently control biophysical properties such as stiffness and pore size. Here, we present a 3D tension bioreactor system that permits precise mechanical tuning of collagen hydrogel stiffness, while maintaining consistent composition and pore size. We achieve this by mechanically loading collagen hydrogels covalently-conjugated to a polydimethylsiloxane (PDMS) membrane to induce hydrogel stiffening. We validated the biological application of this system with oncogenically transformed mammary epithelial cell organoids embedded in a 3D collagen I hydrogel, either uniformly stiffened or calibrated to create a gradient of ECM stiffening, to visually demonstrate the impact of ECM stiffening on transformation and tumor cell invasion. As such, this bioreactor presents the first tunable 3D natural hydrogel system that is capable of independently assessing the role of ECM stiffness on tissue phenotype.

Keywords
Cell culture; Bioreactor; 3D collagen hydrogel; ECM stiffness; Mechanotransduction
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A 3D tension bioreactor platform to study the interplay between ECM stiffness and tumor phenotype
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Publisher
Database: Elsevier - ScienceDirect
Journal: Journal of Biotechnology - Volume 193, 10 January 2015, Pages 66–69
Authors
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Subjects
Physical Sciences and Engineering Chemical Engineering Bioengineering
Get Full-Text Now
Don't Miss Today's Special Offer
Price was $35.95
You save - $31
Price after discount Only $4.95
100% Money Back Guarantee
Full-text PDF Download
Online Support
Any Questions? feel free to contact us