(621e) Design of A Biomimetic Nanostructured Tissue Engineered Bone Model for in Vitro Breast Cancer Metastasis Study

Breast cancer is the leading cause of cancer-related death in American women, accounting for more than 200,000 new cases and 40,000 deaths annually. Majority of advanced breast cancer patients will eventually develop bone metastasis. However, the cure and treatment of metastasis breast cancer is still very challenging because of insufficient knowledge about underlying metastasis mechanisms. Traditional tumor metastasis models (in vivo and in vitro) contain inherent limitations with regards to controllability, reproducibility, and flexibility. To solve the above problems, this research designs an easy-to-use and biomimetic 3D nanostructured bone model via natural chitosan and various hydroxyapatites (HA) for breast cancer metastasis study. 3D porous chitosan-HA scaffolds with different crystalline, size and concentration of HA (specifically, 10% and 20% nanocrystalline HA, microcrystalline HA and amorphous HA) were fabricated via a lyophilization procedure. Human MDA-MB231 metastasis breast cancer cells were seeded at 50000 cells/scaffold. After 24h cell culture, the cell adhesion and growth result reveals that concentration, size and crystallinity of HA have a significant impact on metastasis breast cancer cell behavior. 10% nanocrystalline HA can significantly increase breast cancer cell attachment when compared to all of other HA. Since natural bone matrix is made of rich nanocrystalline HA, our synthesized nanocrystalline HA in chitosan can create a more bone-like environment for breast cancer cell metastasis when compared to microcrystalline and amorphous HA. Furthermore, 20% nanocrystalline HA in chitosan shows the similar increasing trend for cancer cell attachment when compared to respective 20% microcrystalline HA in chitosan. In addition, the result reveals that lower concentration of HA (10%) can promote more breast cancer cell growth than higher concentration of HA (20%) in chitosan. Based on the result, 10 % nanocrystalline HA-chitosan scaffold can significantly improve more breast cancer cell growth than other size, concentration and crystallinity of HA chitosan scaffold, thus make it promising for further breast cancer cell metastasis study.