Understanding Cancer Cell Behavior Through 3D Printed Bone Microenvironments

Abstract

Cancer is a significant health problem worldwide and forms through orchestrated and highly complex biological processes. This process is mediated through biophysical and biochemical signals that develop from within the tumor microenvironment. Although two-dimensional culture systems of established breast cancer cell lines are the most widely used model for cancer biology and preclinical drug assessments, it poorly mimics the behavior of cancer cells in vivo and fails to reproduce the in vivo tumor microenvironment, and accordingly, the data it produces is not always predictive. Effective therapeutic strategies require a cost-efficient in vitro model that can more accurately resemble the in vivo tumor microenvironment, thus permitting a variety of in vitro studies. Rapid prototyping (RP) is one of the most promising techniques for designing and producing three-dimensional (3D) systems (hydrogels, scaffolds) for drug efficacy analysis, developing drug delivery systems, and tissue engineering applications. The application of 3D bioprinting in engineering a cancer cell microenvironment will be the focus of this chapter. We will describe previous model systems used to understand cancer cell behavior. In particular, bioprinting methods and strategies that emphasize recreation of a cancer microenvironment that promotes cultured cancer cells to express a more relevant phenotype will be examined. Our focus will be on the 3D bioprinted models that serve as a predictive model for understanding mechanisms leading to cancer cell metastasis, permit real-time study of cell-cell interactions, enable the analysis of growth factors and cytokine expression that supports tumor cell growth or survival, and the molecular cross-talk between tumor and stromal cells. The chapter will conclude with an assessment of the current state-of-the-art and future prospects.