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Background During wound healing, the overproduction of reactive oxygen species (ROS) can break the cellular oxidant/antioxidant balance, which prolongs healing. The wound dressings targeting the mitigation of ROS will be of great advantages for the wound healing. puerarin (PUE) and ferulic acid (FA) are natural compounds derived from herbs that exhibit multiple pharmacological activities, such as antioxidant and anti-inflammatory effects. Polydopamine (PDA) is made from natural dopamine and shows excellent antioxidant function. Therefore, the combination of natural antioxidants into hydrogel dressing is a promising therapy for wound healing. Results Hydrogel wound dressings have been developed by incorporating PUE or FA via PDA nanoparticles (NPs) into polyethylene glycol diacrylate (PEG-DA) hydrogel. This hydrogel can load natural antioxidant drugs and retain the drug in the gel network for a long period due to the presence of PDA NPs. Under oxidative stress, this hydrogel can improve the activity of superoxide dismutase and glutathione peroxidase and reduce the levels of ROS and malondialdehyde, thus preventing oxidative damage to cells, and then promoting wound healing, tissue regeneration, and collagen accumulation. Conclusion Overall, this triple antioxidant hydrogel accelerates wound healing by alleviating oxidative injury. Our study thus provides a new way about co-delivery of multiple antioxidant natural molecules from herbs via antioxidant nanoparticles for wound healing and skin regeneration. Graphic Abstract

Oxidative damage generated would disrupt the oxidant/antioxidant balance in cells, causing slow wound healing and tissue regeneration. Hydrogel dressing with antioxidant properties can promote wound healing, however, its design is still a challenge.

Transdermal drug delivery is an attractive, non-invasive treatment.

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