Hyaluronan as tunable drug delivery system

Abstract

The hyaluronan (HA) polymer is an important macromolecule of extracellular matrix with remarkable structure and functions: it is a linear and unbranched polymer without sulphate or phosphate groups and has key role in several biological processes in mammals. It is ubiquitous in mammalian tissues with several and specific functions, influencing cell proliferation and migration as well as angiogenesis and inflammation. To exert these important functions in tissues HA modifies the concentration and size. Considering this HA content in tissues is carefully controlled by different mechanisms including covalent modification of the synthetic enzymes and epigenetic control of their gene expression. The function of HA is also critical in several pathologies including cancer, diabetes and chronic inflammation. Among these biological roles, the structural properties of HA allow to use this polymer in regenerative medicine including cosmetics and drug delivery. HA takes advantage from its capacity to form gels even at concentration of 1% producing scaffolds with very intriguing mechanical properties. These hydrogels are useful in regenerative medicine as biocompatible material for advanced therapeutic uses. In this review we highlight the biological aspects of HA addressing the mechanisms controlling the HA content in tissues and its role as drug delivery system.

Keywords: Extracellularmatrix; Glycosaminoglycans; HA; Hyaluronan; Hyaluronidase; Hydrogel; O-GlcNAcylation; Proteoglycans; UDP-sugars.