Modeling 3D Cancer Cell Microenvironment Using Physically Associated Stiffness Gradient Gels

Abstract

Numerous advancements have made significant contributions to not only our ability to detect and treat cancer but has also expanded our understanding of cancer pathology. One such advancement comes from the ability to model cancer through three-dimensional (3D) methodologies to mimic the tumor microenvironment (TME). One present 3D modeling technique employs the use of biomaterials (BMs) in the form of physically crosslinked hydrogels (HGs) using polymers/copolymers derived from natural (i.e., collagen) and synthetic (i.e., PLGA, PLA) materials. The utilization of HGs has allowed for the emulation of the reciprocal communication that exists between cells and their microenvironment of specific tissues and organ systems. This ability of microenvironment emulation is critical in the study of cancer, as cancers have a particular environment that supports the survival and progression of cancer. While the use of HGs in 3D modeling has had its successes, there are pitfalls of using BMs that require extensive crosslinking. Therefore, researchers have been exploring the use of non-crosslinked BMs as 3D platforms for culturing and modeling. Cancer can affect every type of tissue and organ system as they develop, grow, and possibly metastasize. The variability that exists among natural tissue types makes it difficult to mimic a specific tissue’s microenvironment. Here we focused on developing a non-crosslinked BM to mimic the TME with a stiffness gradient and demonstrated the viability of cancer cells in physically associated, stiffness gradient, granular network HGs (GNHGs). Future applications of our GNHG platform includes the incorporation of additional cellular and non-cellular components, the application of other polymers, and applying our methodology towards the various aspects and practices in biomedical engineering.