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 in to other tissues. Twodimensional (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.

Biophysics Role and Biomimetic Culture Systems of ECM Stiffness in Cancer EMT

“…In comparison to the onefold ECM protein scaffold currently used in cell culture systems, dECM retains the unabridged biochemical complexity of natural tissues, providing the closest to physiological conditions and a tissue‐specific microenvironment. [ 114 ] However, the lack of methods to control the mechanical properties of dECM materials limits their application in exploring organizational structure and mechanical properties. [ 115 ]…”

Instructive Hydrogels for Primary Tumor Cell Culture: Current Status and Outlook

“…[ 135 ] Alginate hydrogels were widely used in stiffness driven differentiation of stem cells and tumorigenic ability of normal mammary epithelial cells. [ 136 ]…”

Resolving Metabolic Heterogeneity in Experimental Models of the Tumor Microenvironment from a Stable Isotope Resolved Metabolomics Perspective

“…It is also practical to use matrix-free magnetic-bead-based 3D culture method for metabolic studies [121]. In some systems, spheroids or organoids form without added matrix support, as the cells generate their own ECM [106,165,166]. In the latter two cases, control of the medium compositions and metabolic quenching will be straightforward, as the case for 2D cell culture studies.…”