Extracellular Matrix Mimics Using Hyaluronan-Based Biomaterials

Hyaluronan (HA) is a critical element of the extracellular matrix (ECM). The regulated synthesis and degradation of HA modulates the ECM chemical and physical properties that, in turn, influence cellular behavior. HA triggers signaling pathways associated with the adhesion, proliferation, migration, and differentiation of cells, mediated by its interaction with specific cellular receptors or by tuning the mechanical properties of the ECM. This review summarizes the recent advances on strategies used to mimic the HA present in the ECM to study healthy or pathological cellular behavior. This includes the development of HA-based 2D and 3D in vitro tissue models for the seeding and encapsulation of cells, respectively, and HA particles as carriers for the targeted delivery of therapeutic agents. The extracellular matrix is composed of hyaluronan of different molecular weights that play different roles in cellular proliferation, migration, and differentiation.The dysregulated accumulation of hyaluronan alters the mechanical and biochemical properties of the extracellular matrix and it is associated with several pathological states.Biomaterials can be engineered using the native hyaluronan backbone or chemically modified to target cells via specific cellular receptors, such as CD44.2D surfaces with controlled topography and 3D hydrogels with tuned mechanical properties and hyaluronan composition can be designed to mimic the bioactivity of this glycosaminoglycan in the ECM.