Role of Hyaluronan in Wound Healing

Hyaluronan is a negatively charged high molecular weight connective tissue glycosaminoglycan (GAG). As well as heparin sulfate proteoglycan, hyaluronan is a major polysaccharide found in extra cellular matrix (ECM). Hyaluronan is mainly synthesized by mesenchymal cells and extruded into ECM in coordination with synthesis. Hyaluronan molecules form a continuous but porous meshwork structure. This property of hyaluronan may contribute to the hydrated microenvironment at sites of synthesis. Together with passive functions such as space filling molecule, hyaluronan interacts with cell surface receptors, and regulates cell function by activating intracellular signaling pathway. Hyaluronan is taken up by cell surface receptors for intracellular degradation. The degradation occurs in stepwise fashion by distinct enzymes, hyaluronidase-1 (HYAL1) and HYAL2. Hyaluronan fragment has distinct functions that are not found in normal high molecular weight hyaluronan. High molecular weight hyaluronan acts as a component of intact ECM and tends to maintain signals that promote normal cellular functions whereas hyaluronan fragment tends to induce cellular differentiation, tissue morphogenesis or tissue defense in response to injury. Consequently, hyaluronan exerts beneficial effects on many steps of wound healing process such as inflammation, reepithelialization and resolution.