Reductionist Three-Dimensional Tumor Microenvironment Models in Synthetic Hydrogels

Simple Summary: Tumors exist in a complex, three-dimensional environment which helps them to survive, grow, metastasize, and resist drug treatment. Simple, reproducible, in vitro models of this environment are necessary in order to better understand tumor behavior. Naturally derived polymers are great 3D cell culture substrates, but they often lack the tunability and batch-to-batch consistency which can be found in synthetic polymer systems. In this review, we describe the current state of and future directions for tumor microenvironment models in synthetic hydrogels. Tumors exist in a complex, three-dimensional environment which helps them to survive, grow, metastasize, and resist drug treatment. Simple, reproducible, in vitro models of this environment are necessary in order to better understand tumor behavior. Naturally derived polymers are great 3D cell culture substrates, but they often lack the tunability and batch-to-batch consistency which can be found in synthetic polymer systems. In this review, we describe the current state of and future directions for tumor microenvironment models in synthetic hydrogels. The tumor microenvironment (TME) plays a determining role in everything from disease progression to drug resistance. As such, in vitro models which can recapitulate the cell-cell and cell-matrix interactions that occur in situ are key to the investigation of tumor behavior and selecting effective therapeutic drugs. While naturally derived matrices can retain the dimensionality of the native TME, they lack tunability and batch-to-batch consistency. As such, many synthetic polymer systems have been employed to create physiologically relevant TME cultures. In this review, we discussed the common semi-synthetic and synthetic polymers used as hydrogel matrices for tumor models. We reviewed studies in synthetic hydrogels which investigated tumor cell interactions with vasculature and immune cells. Finally, we reviewed the utility of these models as chemotherapeutic drug-screening platforms, as well as the future directions of the field.