title: Engineering a biomimetic three-dimensional nanostructured bone model for breast cancer bone metastasis study.
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.
authors.affiliation: Department of Mechanical and Aerospace Engineering, The George Washington University, Washington, DC 20052, USA.
authors.forename: Wei
authors.initials: W
authors.lastname: Zhu
authors.affiliation: Department of Mechanical and Aerospace Engineering, The George Washington University, Washington, DC 20052, USA.
authors.forename: Mian
authors.initials: M
authors.lastname: Wang
authors.affiliation: Division of Genomic Medicine, Department of Medicine, The George Washington University Medical Center, Washington, DC 20052, USA.
authors.forename: Yebo
authors.initials: Y
authors.lastname: Fu
authors.affiliation: Department of Mechanical and Aerospace Engineering, The George Washington University, Washington, DC 20052, USA.
authors.forename: Nathan J
authors.initials: NJ
authors.lastname: Castro
authors.affiliation: Division of Genomic Medicine, Department of Medicine, The George Washington University Medical Center, Washington, DC 20052, USA.
authors.forename: Sidney W
authors.initials: SW
authors.lastname: Fu
authors.affiliation: Department of Mechanical and Aerospace Engineering, The George Washington University, Washington, DC 20052, USA; Division of Genomic Medicine, Department of Medicine, The George Washington University Medical Center, Washington, DC 20052, USA. Electronic address: lgzhang@gwu.edu.
authors.forename: Lijie Grace
authors.initials: LG
authors.lastname: Zhang
mesh_terms: D040761:Biomimetic Materials / Q000737:chemistry / Q000494:pharmacology*; D001859:Bone Neoplasms / Q000556:secondary*; D001943:Breast Neoplasms / Q000473:pathology*; D002454:Cell Differentiation / Q000187:drug effects; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D048271:Chitosan / Q000494:pharmacology; D003460:Crystallization; D017886:Durapatite / Q000494:pharmacology; D005260:Female; D006801:Humans; D021621:Imaging, Three-Dimensional; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000187:drug effects / Q000648:ultrastructure; D046529:Microscopy, Electron, Transmission; D008954:Models, Biological; D049329:Nanostructures / Q000737:chemistry*; D009361:Neoplasm Invasiveness; D010012:Osteogenesis / Q000187:drug effects; D023822:Tissue Engineering / Q000379:methods*; D054457:Tissue Scaffolds
chemical_list: D048271:Chitosan; D017886:Durapatite
keywords: Biomimetic; Bone model; Breast cancer; Metastasis; Nanomaterial