Smart Release of the Antioxidant from Chitosan-Hyaluronan Reservoir in Skin Wound Healing

Reactive oxygen species (ROS) play a dual role in biological systems as indispensable signaling molecules and as key mediators of oxidative damage. Chronic wounds are often associated with excessive ROS formation, which impedes the healing process. Locally applied antioxidants may mitigate such imbalance and support tissue regeneration. The chitosan-hyaluronan (Ch/HA) composite membranes' biocompatibility, moisture retention, and ability to maintain local redox balance rank these materials among the most promising next-generation wound dressings. The aim of this review is to summarize the Ch/HA composite membranes serving as reservoirs for locally applied antioxidants to accelerate the healing of full-thickness skin wounds in experimental animals. Composite Ch/HA membranes fortified with the selected antioxidants such as phosphatidylcholine dihydroquercetin and glutathione were evaluated in rats. A mitochondria-targeted derivative such as mitoquinone mesylate was evaluated in rats and rabbits, while l-(+)-ergothioneine has been examined in rabbits so far. This review demonstrates that smartly designed Ch/HA composite membranes represent a novel-generation wound dressing platform capable of smart antioxidant release and efficient stimulation of skin regeneration.