Extracellular Matrix Mimics Using Hyaluronan-Based Biomaterials

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. 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. 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. characteristic of a material/matrix related to its ability to exert a biological function. bone morphogenetic protein 6, known for their ability to induce the growth of bone and cartilage, upregulating osteogenic markers in mesenchymal stem cells. myoblasts cell line derived from mouse muscle tissue. calcium carbonate typically used for the preparation of nano-/microparticles as inorganic templates. a transmembrane cell surface glycoprotein with a link module to hyaluronan. extracellular signal-regulated kinase 1 and 2, involved in the signaling cascades that regulate the cells adhesion, proliferation, migration, cell survival, and differentiation. tridimensional network composed of proteins, glycoproteins, glycosaminoglycan, proteoglycans, and cytokines that provides structural and biochemical support to cells. focal adhesion kinase that regulates the cellular movement and the remodeling of the cytoskeleton, crucial for the migration of cells. polysaccharides present in human tissues. hyaluronan binding protein, responsible for different cellular functions. hyaluronan receptor for endocytosis mediates the systemic clearance of hyaluronan. hyaluronan synthase, a transmembrane enzyme responsible for production and extrusion of hyaluronan to the extracellular space. biological, chemical, and physical equilibrium maintained in living tissues. hyaluronan-binding proteins. hyaluronidases, an intra- and extracellular enzyme responsible for the degradation of hyaluronan. an assembly technique based on the deposition of oppositely charged polyelectrolytes to form a multilayered thin film. lymphatic vessel endothelial receptor for hyaluronan, a membrane glycoprotein with an extracellular link domain. the capacity of a material to induce cellular signaling in response to a mechanical stimulus. human non-small cell lung cancer polyethylene glycol, a hydrophilic molecule with different biomedical, chemical, and industrial applications. polyethyleneimine, a linear or branched aliphatic polyamine. poly-l-lysine, a positively charged polyelectrolyte. receptor for hyaluronan-mediated motility. protein involved in the regulation of cell adhesion, morphology, polarity, and migration through the activation of signal transduction pathways. reactive oxygen species, consisting of radical and nonradical oxygen species. silicon dioxide. small interfering RNA or silencing RNA. smooth muscle cells, crucial in the formation and function of the cardiovascular, respiratory, and digestive systems, among others. transforming growth factor-β1. tumor necrosis factor-stimulated gene-6. titanium dioxide. toll-like receptors, a transmembrane protein located in the plasma membrane (TLR 1,2,4,5, and 6) and in the membranes of endosomes and lysosomes (TLRs 3, 7, 8, and 9), that can detect human pathogens. yes-associated protein, an oncoprotein located in the cytoplasm that is responsive to the external mechanical stimuli.