Engineering a biomimetic three-dimensional nanostructured bone model for breast cancer bone metastasis study. (1st March 2015)

• Record Type: Journal Article
• Authors: Zhu, Wei; Wang, Mian; Fu, Yebo; Castro, Nathan J.; Fu, Sidney W.; Zhang, Lijie Grace
• Is Part Of: Acta biomaterialia. Volume 14(2015)
• Page Start: 164
• Page End: 174
• Publication Date: 2015-03-01
• Subjects: Bone model -- Biomimetic -- Nanomaterial -- Breast cancer -- Metastasis; Biomedical materials -- Periodicals; 610.28
• DOI: 10.1016/j.actbio.2014.12.008
• Languages: English
• ISSNs: 1742-7061

Abstract

Graphical abstract: Abstract: Traditional breast cancer (BrCa) bone metastasis models contain many limitations with regards to controllability, reproducibility and flexibility of design. In this study, a novel biomimetic bone microenvironment was created by integrating hydroxyapatite (HA) and native bioactive factors deposited by osteogenic induction of human bone marrow mesenchymal stem cells (MSCs) within a cytocompatible chitosan hydrogel. It was found that a 10% nanocrystalline HA (nHA) chitosan scaffold exhibited the highest BrCa adhesion and proliferation when compared to chitosan scaffolds with 20% nHA, 10% and 20% microcrystalline HA as well as amorphous HA. This 3-D tunable bone scaffold can provide a biologically relevant environment, increase cell–cell and cell–matrix interactions as found in native bone, and retain the behavior of BrCa cells with different metastasis potential (i.e. highly metastatic MDA-MB-231, less metastatic MCF-7 and transfected MDA-MB-231). The co-culture of MSCs and MDA-MB-231 in this bone model illustrated that MSCs have the capacity to upregulate the expression of the well-known metastasis-associated gene metadherin within BrCa cells. In summary, this study illustrates the ability of our 3-D bone model to create a biomimetic environment conducive to recapitulating the behavior of metastatic BrCa cells, making it a promising tool for in vitro BrCa cell bone metastasis study and for the discovery of potential therapeutics.