title: A 3D printed nano bone matrix for characterization of breast cancer cell and osteoblast interactions.
abstract: Bone metastasis is one of the most prevalent complications of late-stage breast cancer, in which the native bone matrix components, including osteoblasts, are intimately involved in tumor progression. The development of a successful in vitro model would greatly facilitate understanding the underlying mechanism of breast cancer bone invasion as well as provide a tool for effective discovery of novel therapeutic strategies. In the current study, we fabricated a series of in vitro bone matrices composed of a polyethylene glycol hydrogel and nanocrystalline hydroxyapatite of varying concentrations to mimic the native bone microenvironment for the investigation of breast cancer bone metastasis. A stereolithography-based three-dimensional (3D) printer was used to fabricate the bone matrices with precisely controlled architecture. The interaction between breast cancer cells and osteoblasts was investigated in the optimized bone matrix. Using a Transwell®system to separate the two cell lines, breast cancer cells inhibited osteoblast proliferation, while osteoblasts stimulated breast cancer cell growth, whereas, both cell lines increased IL-8 secretion. Breast cancer cells co-cultured with osteoblasts within the 3D bone matrix formed multi-cellular spheroids in comparison to two-dimensional monolayers. These findings validate the use of our 3D printed bone matrices as an in vitro metastasis model, and highlights their potential for investigating breast cancer bone metastasis.
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.forename: Nathan J
authors.initials: NJ
authors.lastname: Castro
authors.forename: Haitao
authors.initials: H
authors.lastname: Cui
authors.forename: Xuan
authors.initials: X
authors.lastname: Zhou
authors.forename: Benchaa
authors.initials: B
authors.lastname: Boualam
authors.forename: Robert
authors.initials: R
authors.lastname: McGrane
authors.forename: Robert I
authors.initials: RI
authors.lastname: Glazer
authors.forename: Lijie Grace
authors.initials: LG
authors.lastname: Zhang