Emerging Biomimetic Materials for Studying Tumor and Immune Cell Behavior

Abstract

Cancer is one of the leading causes of death both in the United States and worldwide. The dynamic microenvironment in which tumors grow consists of fibroblasts, immune cells, extracellular matrix (ECM), and cytokines that enable progression and metastasis. Novel biomaterials that mimic these complex surroundings give insight into the biological, chemical, and physical environment that cause cancer cells to metastasize and invade into other tissues. Two-dimensional (2D) cultures are useful for gaining limited information about cancer cell behavior; however, they do not accurately represent the environments that cells experience in vivo. Recent advances in the design and tunability of diverse three-dimensional (3D) biomaterials complement biological knowledge and allow for improved recapitulation of in vivo conditions. Understanding cell-ECM and cell-cell interactions that facilitate tumor survival will accelerate the design of more effective therapies. This review discusses innovative materials currently being used to study tumor and immune cell behavior and interactions, including materials that mimic the ECM composition, mechanical stiffness, and integrin binding sites of the tumor microenvironment.

Keywords: Biomimetic; Cell–ECM interactions; Epithelial-to-mesenchymal transition; Extracellular matrix.

FIGURE 1.

The tumor microenvironment and its components, including tumor cells, immune cells, stromal cells, ECM, and soluble factors.

FIGURE 2.

ECM-cell interactions.

FIGURE 3.

Normal tissue and tumor organoid model systems and uses. Tumor organoid model systems can be produced from tumors or by genetic modification of organoids generated from normal tissues. Organoids can be used to answer questions about cancer biology, cell–cell interaction studies, and therapy response mechanisms.

FIGURE 4.

The process of deriving decellularized ECM from various organs for hydrogel formation.^,,,,

FIGURE 5.

Biomimetic materials have been developed to span the stiffness range observed in (a) the epithelial-to-mesenchymal transition (EMT) and (b) commonly studied tissues and organs.^,,,