Nanofabricated Biomaterials Model Tumor Extracellular Matrix Topography

In vitro studies of cancer cell behavior are often limited in translational capability due to the absence of in vivo characteristics, such as the tumor microenvironment (TME), that largely govern this behavior. The TME includes a dense, highly organized network of proteins that forms the extracellular matrix (ECM). In many cancers, the ECM of the TME is distinct from that of healthy tissue in that it is highly aligned and crosslinked, forming a stiff matrix that serves as a structural scaffold for cancer cells. Notably, the TME ECM and its unique topography at the micro‐ and nanoscale have demonstrated profound influence on cell polarity, migration, invasion, and proliferation capabilities. Thus, proper recapitulation of the TME ECM is crucial for in vitro assessment of cancer cell behavior that accurately models in vivo processes. Nanofabricated biomaterials have emerged as versatile tools for the recapitulation of the nanoscale topography of the TME ECM. In this review, we discuss the various geometries of nanofabricated biomaterial scaffolds employed for 2D in vitro assays and their benefits and limitations. We additionally introduce our collagen‐coated nanogrooved array and its utility in modeling the ECM of understudied pediatric malignancies, including neuroblastoma.