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Hyaluronic acid (HA) is a natural polysaccharide and a key component of the extracellular matrix (ECM) in many tissues. Therefore, HA-based biomaterials are extensively utilized to create three dimensional ECM mimics to study cell behaviors in vitro . Specifically, derivatives of HA have been commonly used to fabricate hydrogels with controllable properties. In this review, we discuss the various chemistries employed to fabricate HA-based hydrogels as a tunable matrix to mimic the cancer microenvironment and subsequently study cancer cell behaviors in vitro . These include Michael-addition reactions, photo-crosslinking, carbodiimide chemistry, and Diels–Alder chemistry. The utility of these HA-based hydrogels to examine cancer cell behaviors such as proliferation, migration, and invasion in vitro in various types of cancer are highlighted. Overall, such hydrogels provide a biomimetic material-based platform to probe cell-matrix interactions in cancer cells in vitro and study the mechanisms associated with cancer progression.
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