Microfabrication-Based Three-Dimensional (3-D) Extracellular Matrix Microenvironments for Cancer and Other Diseases

Exploring the complicated development of tumors and metastases needs a deep understanding of the physical and biological interactions between cancer cells and their surrounding microenvironments. One of the major challenges is the ability to mimic the complex 3-D tissue microenvironment that particularly influences cell proliferation, migration, invasion, and apoptosis in relation to the extracellular matrix (ECM). Traditional cell culture is unable to create 3-D cell scaffolds resembling tissue complexity and functions, and, in the past, many efforts were made to realize the goal of obtaining cell clusters in hydrogels. However, the available methods still lack a precise control of cell external microenvironments. Recently, the rapid development of microfabrication techniques, such as 3-D printing, microfluidics, and photochemistry, has offered great advantages in reconstructing 3-D controllable cancer cell microenvironments in vitro. Consequently, various biofunctionalized hydrogels have become the ideal candidates to help the researchers acquire some new insights into various diseases. Our review will discuss some important studies and the latest progress regarding the above approaches for the production of 3-D ECM structures for cancer and other diseases. Especially, we will focus on new discoveries regarding the impact of the ECM on different aspects of cancer metastasis, e.g., collective invasion, enhanced intravasation by stress and aligned collagen fibers, angiogenesis regulation, as well as on drug screening.