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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., (© 2021. The Author(s).)

Oxidative damage generated by various biochemical pathways can disrupt the oxidant/antioxidant balance in cells, causing slow wound healing and tissue regeneration; in this regard, a hydrogel dressing with antioxidant properties can promote wound healing; however, its design is still a challenge. Herein, a polydopamine/puerarin (PDA/PUE) nanoparticle-incorporated polyethylene glycol diacrylate hybrid hydrogel (PEG-DA/PDA/PUE) with antioxidant properties was prepared and used as a wound-healing material. Experimental observations indicated that the PEG-DA/PDA/PUE hydrogel possessed excellent swelling capacity and mechanical property. Moreover, the antioxidant capability was enhanced with an increase in the concentration of polydopamine/puerarin nanoparticles in the hydrogel. The hydrogel presented good cell proliferation and antioxidant activity, including a decrease in ROS and increase in the superoxide dismutase (SOD) and glutathione peroxidase (GPx) activity under oxidative stress conditions. Furthermore, the full-thickness skin-defect-regeneration process could be accelerated via the antioxidant hydrogel treatment. This study validated the potential applications of an antioxidant hydrogel for wound healing.

• Enhance antioxidant activity of hydrogel is a promising way for wound healing. • The well-designed hybrid hydrogel is natural and simple. • Arginine derivatives enhance the dopamine antioxidation for hyaluronic acid hydrogel. Scaffolds with antioxidant capability have attracted considerable interests for wound healing. For enhanced wound healing, new antioxidant materials are still highly needed. In this study, new antioxidant materials, arginine derivatives (AD), were introduced into dopamine-functionalized hyaluronic acid (HA-DA) to develop novel hydrogels (HA-DA/AD) with enhanced antioxidant activity. The HA-DA/AD hydrogels showed greater DPPH and hydroxyl radical scavenging rates than the HA-DA hydrogel. Moreover, the HA-DA/AD hydrogels exhibited significantly better protection for cells against external oxidative stress (decreased ROS and MDA levels and increased SOD and GPx enzyme activity) and better wound healing (enhanced VEGF and CD 31 expression and enhanced tissue remodeling). This study confirmed that AD could assist wound healing scaffolds to have enhanced antioxidant properties. [ABSTRACT FROM AUTHOR]