Hyaluronan in wound healing: Rediscovering a major player

Wound healing involves a series of carefully modulated steps, from initial injury and blood clot to the final reconstituted tissue or scar. A dynamic reciprocity exists throughout between the wound, blood elements, extracellular matrix, and cells that participate in healing. Multiple cytokines and signal transduction pathways regulate these reactions. A major component throughout most of the process is hyaluronan, a straight‐chain carbohydrate extracellular matrix polymer. Hyaluronan occurs in multiple forms, chain length being the only distinguishing characteristic between them. Levels of hyaluronan in its high–molecular‐weight form are prominent in the earliest stages of wound repair. Progressively more fragmented forms occur in a manner not previously appreciated. We outline here steps in the wound healing cascade in which hyaluronan participates, as well as providing a review of its metabolism. Although described by necessity in a series of quantum steps, the healing process is constituted by a smooth continuum of overlapping reactions. The prevalence of hyaluronan in the wound (initially termed “hexosamine‐containing mucopolysaccharide”), particularly in its early stages, was pointed out over half a century ago by the Harvard surgeon J. Engelbert Dunphy. It appears we are now returning to where we started.