Flow Enabled Tissue Engineered Testbeds for Cancer Metastasis

Bone metastasis of breast cancer and prostate cancer to bone results in over a million deaths each year in the world. Even larger number of patients suffer from skeletal complications affecting the quality of life. In the event of bone metastasis the inefficacy of available anticancer drugs results from the increased drug resistance of the migrated cancer. The lack of availability of patient samples and the failure of animal models results in an acute need for robust in vitro models of cancer metastasis. We report the design of a tissue-engineered bone scaffold seeded with patient-derived cancer cell lines co-cultured with appropriate tumor microenvironment duplicating cells such as cancer-associated fibroblasts and epithelial stromal cells to create realistic bone metastasis testbeds of breast and prostate cancer bone metastasis. The bone scaffold is made using nanoclay polymer composites seeded with human mesenchymal stem cells, recreating the remodeling stage of fetal bone. Further, we have developed a novel horizontal flow bioreactor that mimics the interstitial fluid flow in the scaffolds. The bioreactor also has the ability to mimic the migration of cancer cells in fluid flow to the metastatic bone site. This fluid flow-enabled metastasis testbed is used for screening drugs and the discovery of new markers of metastasis. Thus, by mimicking both the accurate tumor microenvironment of the bone site of metastasis, as well as the migration of cells and their adhesion at the bone site using flow-based bioreactor, the novel testbed presented here is a useful in vitro system for the development of new therapies of metastasis as well as providing methods for personalized medicine.