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Open AccessArticle

3D Perfusable Hydrogel Recapitulating the Cancer Dynamic Environment to in Vitro Investigate Metastatic Colonization

National Research Council of Italy, Institute of Electronic, Computer and Telecommunications (IEIIT) Institute, 16149 Genoa, Italy
Department of Computer Science, Bioengineering, Robotics and Systems Engineering, University of Genoa, 16126 Genoa, Italy
Author to whom correspondence should be addressed.
These authors contributed equally.
Polymers 2020, 12(11), 2467;
Received: 8 October 2020 / Revised: 19 October 2020 / Accepted: 22 October 2020 / Published: 24 October 2020
(This article belongs to the Special Issue Functional Polymer Networks)
Metastasis is a dynamic process involving the dissemination of circulating tumor cells (CTCs) through blood flow to distant tissues within the body. Nevertheless, the development of an in vitro platform that dissects the crucial steps of metastatic cascade still remains a challenge. We here developed an in vitro model of extravasation composed of (i) a single channel-based 3D cell laden hydrogel representative of the metastatic site, (ii) a circulation system recapitulating the bloodstream where CTCs can flow. Two polymers (i.e., fibrin and alginate) were tested and compared in terms of mechanical and biochemical proprieties. Computational fluid-dynamic (CFD) simulations were also performed to predict the fluid dynamics within the polymeric matrix and, consequently, the optimal culture conditions. Next, once the platform was validated through perfusion tests by fluidically connecting the hydrogels with the external circuit, highly metastatic breast cancer cells (MDA-MB-231) were injected and exposed to physiological wall shear stress (WSS) conditions (5 Dyn/cm2) to assess their migration toward the hydrogel. Results indicated that CTCs arrested and colonized the polymeric matrix, showing that this platform can be an effective fluidic system to model the first steps occurring during the metastatic cascade as well as a potential tool to in vitro elucidate the contribution of hemodynamics on cancer dissemination to a secondary site. View Full-Text
Keywords: hydrogels; fibrin; alginate; CFD; metastasis; extravasation hydrogels; fibrin; alginate; CFD; metastasis; extravasation
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Vitale, C.; Fedi, A.; Marrella, A.; Varani, G.; Fato, M.; Scaglione, S. 3D Perfusable Hydrogel Recapitulating the Cancer Dynamic Environment to in Vitro Investigate Metastatic Colonization. Polymers 2020, 12, 2467.

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