Project Title: Development and Validation of a 3D silk fibroin-based model to Accurately Predict Metastatic Breast Cancer Therapy Responses
Research overview. The bone possesses a complex, multicellular, multidimensional and dynamic microenvironment that contributes to tumor growth. The poor predictive power of 2D monoculture models often employed in pre-clinical trials hamper the development of more effective therapies for metastatic cancers and other bone-related diseases. To overcome this obstacle, researchers have proposed the development of accurate and validated protocols employing 3D co-culture models that can reproducibly mimic the bone microenvironment. Accurate and validated models can serve to better predict the potential of a given therapy to succeed clinically before much time and effort is spent. 3D co-culture models are generally superior than 2D monocultures in modeling in vivo cell phenotypes, disease progression, and response to therapeutics. In collaboration, both the López and Peterson laboratories aim to employ silk fibroin scaffolds to understand if a 3D co-culture model could provide a more accurate prediction of tumor growth, cell-cell and cell-matrix interactions, and resulting therapeutic response than the 2D monoculture counterparts. The PR-CLIMB participant will participate on the preparation and characterization of the silk fibroin scaffolds and the testing and validation of the 3D silk fibroin-based model. She/he will determine the IC50 and RCL% of potential therapeutics against osteolytic metastasis employing monocultures and co-culture of human breast cancer (MDA- MB-231) and osteoblasts (hFOB1.19) cell lines in the 3D silk fibroin-based model. The results obtained by the PR-CLIMB participant will be compared with those previously reported using 2D monocultures under the same cell growth conditions.
Skills/Techniques: PR-CLIMB participants will learn about and utilize techniques employed to characterize the silk fibroin scaffolds in terms of their interfacial and rheological properties. She/he will also use straining techniques to track and differentiate cells in the 3D co-culture model. Quality-by-design, statistical analysis, and experimental validation will be an essential part of this research project.
Skills/Techniques: PR-CLIMB participants will learn about and utilize techniques employed to characterize the silk fibroin scaffolds in terms of their interfacial and rheological properties. She/he will also use straining techniques to track and differentiate cells in the 3D co-culture model. Quality-by-design, statistical analysis, and experimental validation will be an essential part of this research project.