The vision for this project is to develop and demonstrate a new, integrative means of studying the complex behavior of cancer cells in breast tissue. The approach centers on the goal of building an in vitro engineered tissue structure that reproduces the in vivo behavior of the normal and cancerous cells and allows manipulation of environmental parameters to build cause and affect models. Specifically, the end-point of the proposed work will be mathematical relationships describing breast cancer cellular and biomolecular behavior as interactive functions of oxygen level and tissue stiffness, and thus an increased understanding of disease mechanisms. The proposed approach will require development of new experimental and analytical tools to fabricate tissues of hierarchical structure and to assess cell behavior within this framework. The key tools to be developed include a 3D tissue fabrication system, realistic mathematical models to relate cancer cell migration and proliferation with tissue oxygen and stiffness levels, and a novel nanoparticle oxygen sensor.
This project will result in the development of a 3D fabrication system and statistical methodology capable of building tissue in repeatable manner. That is, the fabricated tissue may be used as a personalized diagnostic with which to optimize existing therapeutics, develop new drugs, and develop new vaccines. The cross-pollination of ideas and methods between animal science, biology, chemistry, engineering, clinical medicine, and statistics that will result from this proposed work represents a unique training opportunity for the Investigators. Participation on the proposed multi-disciplinary team will provide individual investigators new insights into their own field. Students involved in the proposed program will be immersed in a technically diverse environment including scientists, engineers, and clinicians, and will hone many skills crucial to the 2020 engineer or scientist, including communication, leadership, and teamwork. Through a carefully crafted educational rubric as well as community outreach program, a diverse population of students (K-postgraduate) and educators (K-12) will be engaged.
