The Role of Hyaluronan in Keloid and Hypertrophic Scar Pathogenesis and Treatment

Keloid and hypertrophic scars are products of abnormal wound healing and can cause disfigurement, discomfort, and decreased quality of life. The precise mechanisms of how these scars form remain unclear, and despite several management strategies, there is currently no definitive management approach that prevents recurrence of keloid scars. Hyaluronan (HA) is a polysaccharide with critical functions in inflammation, fibrosis, and skin health. This narrative review explores what is currently known about the role of HA and associated proteins in keloid and hypertrophic scar pathogenesis and management.

The online MEDLINE and EMBASE databases were searched for articles on keloid and hypertrophic scarring and HA from 1946 to 2026. English-language, peer-reviewed articles with empirical evidence examining human keloid scar tissue, animal models, cell-culture models, hyaluronic acid, or hyaluronome-associated genes were included. Twenty-one studies met all inclusion criteria.

HA concentration was diminished in cell-based models of keloid and hypertrophic scars relative to normal skin. Observed aberrant localization of HA was likely related to the altered expression of genes encoding proteins responsible for the synthesis, degradation, binding, and signaling properties of HA. Intralesional and topical applications of HA both improve appearance and reduce recurrence rates of keloid scars in the short term.

Our review suggests that altered HA production, metabolism, and localization play a key role in keloid and hypertrophic scar pathogenesis. While early evidence supports the potential utility of HA in keloid scar treatment, further robust clinical validation is necessary.