Functions of hyaluronan in wound repair

Hyaluronan is a major carbohydrate component of the extracellular matrix and can be found in skin, joints, eyes and most other organs and tissues. It has a simple, repeated disaccharide linear copolymer structure that is completely conserved throughout a large span of the evolutionary tree, indicating a fundamental biological importance. Amongst extracellular matrix molecules, it has unique hygroscopic, rheological and viscoelastic properties. Hyaluronan binds to many other extracellular matrix molecules, binds specifically to cell bodies through cell surface receptors, and has a unique mode of synthesis in which the molecule is extruded immediately into the extracellular space upon formation. Through its complex interactions with matrix components and cells, hyaluronan has multifaceted roles in biology utilizing both its physicochemical and biological properties. These biological roles range from a purely structural function in the extracellular matrix to developmental regulation through effects of cellular behavior via control of the tissue macro- and microenvironments, as well as through direct receptor mediated effects on gene expression. Hyaluronan is also thought to have important biological roles in skin wound healing, by virtue of its presence in high amounts in skin. Hyaluronan content in skin is further elevated transiently in granulation tissue during the wound healing process. In this review, the general physicochemical and biological properties of hyaluronan, and how these properties may be utilized in the various processes of wound healing: inflammation, granulation and reepithelization, are presented.