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Three-Dimensional In Vitro Hydro- and Cryogel-Based Cell-Culture Models for the Study of Breast-Cancer Metastasis to Bone

Institute of Health and Biomedical Innovation, Queensland University of Technology (QUT), 60 Musk Avenue, Kelvin Grove 4059, Australia
Centre in Regenerative Medicine, Queensland University of Technology (QUT), 60 Musk Avenue, Kelvin Grove 4059, Australia
School of Chemistry, Physics and Mechanical Engineering, Science and Engineering Faculty, Queensland University of Technology (QUT), 2 George Street, Brisbane 4001, Australia
Translational Research Institute, Mater Research Institute-University of Queensland, 37 Kent Street, Woolloongabba 4102, Australia
Leibniz Institute of Polymer Research Dresden, Max Bergmann Center of Biomaterials, Hohe Straβe 6, 01069 Dresden, Germany
Center for Regenerative Therapies Dresden, Technische Universität Dresden, Fetscherstraβe 105, 01307 Dresden, Germany
Author to whom correspondence should be addressed.
Cancers 2018, 10(9), 292;
Received: 18 July 2018 / Revised: 22 August 2018 / Accepted: 23 August 2018 / Published: 27 August 2018
(This article belongs to the Special Issue Targeting Bone Metastasis in Cancer)
PDF [7256 KB, uploaded 27 August 2018]


Bone is the most common site for breast-cancer invasion and metastasis, and it causes severe morbidity and mortality. A greater understanding of the mechanisms leading to bone-specific metastasis could improve therapeutic strategies and thus improve patient survival. While three-dimensional in vitro culture models provide valuable tools to investigate distinct heterocellular and environmental interactions, sophisticated organ-specific metastasis models are lacking. Previous models used to investigate breast-to-bone metastasis have relied on 2.5D or singular-scaffold methods, constraining the in situ mimicry of in vitro models. Glycosaminoglycan-based gels have demonstrated outstanding potential for tumor-engineering applications. Here, we developed advanced biphasic in vitro microenvironments that mimic breast-tumor tissue (MCF-7 and MDA-MB-231 in a hydrogel) spatially separated with a mineralized bone construct (human primary osteoblasts in a cryogel). These models allow distinct advantages over former models due to the ability to observe and manipulate cellular migration towards a bone construct. The gels allow for the binding of adhesion-mediating peptides and controlled release of signaling molecules. Moreover, mechanical and architectural properties can be tuned to manipulate cell function. These results demonstrate the utility of these biomimetic microenvironment models to investigate heterotypic cell–cell and cell–matrix communications in cancer migration to bone. View Full-Text
Keywords: breast cancer; hydrogel; bone metastasis; osteoblasts; 3D model breast cancer; hydrogel; bone metastasis; osteoblasts; 3D model

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Bray, L.J.; Secker, C.; Murekatete, B.; Sievers, J.; Binner, M.; Welzel, P.B.; Werner, C. Three-Dimensional In Vitro Hydro- and Cryogel-Based Cell-Culture Models for the Study of Breast-Cancer Metastasis to Bone. Cancers 2018, 10, 292.

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