Effect of Ergothioneine on the Stability of Hyaluronic Acid-Based Wound-Healing Materials

Hyaluronic acid (HA)-based hydrogels are widely used as wound-healing materials and topical delivery systems because of their excellent biocompatibility, water retention capacity, and ability to promote cell migration. However, HA is prone to oxidative chain scission, which reduces molecular weight and compromises formulation stability and functional performance. This study evaluated the feasibility of ergothioneine (EGT) as a candidate antioxidant stabilizing excipient in a model HA-based wound-healing material. CCK-8 assays assessed the biocompatibility of EGT in L929 mouse fibroblasts after 24 h of exposure, and a stress-screening framework including Fenton oxidation, high-temperature/high-humidity treatment, light exposure, and quiescent storage at 4 °C was established. The results showed that Fenton oxidation markedly induced HA degradation, whereas EGT incorporation effectively protected HA structural integrity under oxidative stress. Cell scratch assays further demonstrated that EGT did not interfere with the ability of HA to promote cell migration. EGT may serve as a candidate antioxidant stabilizing excipient for HA-based wound-healing materials, improving HA structural and material stability under oxidative challenge while preserving HA-associated cell-migration function.