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Patients with advanced breast cancer frequently develop osteolytic bone metastases resulting in significant morbidity and mortality, but treatment options are lacking due to limited understanding of the underlying mechanisms. Historically, bone metastasis research has focused on cancer cells and how they induce clinically evident bone degradation. However, bone metastasis is a multi-step process, the pathogenesis of which depends on the coordinated interplay between many different cell types and their surrounding extracellular matrix (ECM). Tissue-engineered model systems that systematically incorporate both biological and biophysical design parameters, such as cellular interactions and bone ECM composition, architecture, and mechanical properties, will further our understanding of the mechanisms that govern all stages of the metastatic cascade. Here, we briefly summarize current knowledge of bone metastasis and how biomaterial-based models can be used to advance studies of tumor cell dissemination, dormancy, and metastatic outgrowth in the skeleton. Tissue-engineered bone metastasis models will advance comprehension of the crosstalk between cancer cells and the skeletal microenvironment that will lead to the development of more efficacious therapies to interfere with bone metastasis.

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