During the occurring of cutaneous trauma, increasing oxidative stress response in wound site retards the progress of proliferation phase, impeding sequent efficient wound repair. At the same time, high-quality healing also requires adequate new blood vessels in order to furnish the wound site with a nutrient and oxygen-sufficient environment. Here we synthesized a novel hyaluronic acid (HA) material modified with a peroxidation inhibitor 2,2,6,6-tetramethylpiperidinyloxy (ATEMPO) for prevention of excessive reactive oxygen species (ROS) and promotion of angiogenesis after full-thickness skin excision in rats. Amines in ATEMPO attaching with carbonyls in HA chains was fabricated through N-acylation. The HA-g-TEMPO exerted a ROS-scavenging and angiogenesis-promoting function in vitro. In acute wound rat model, the wound closure efficacy was significantly improved to almost 55% at day 6 in comparison to 49% of HA, and wound sites in initial wound phase was also narrowed down sharply. Moreover, initially formed blood vessels were found in wound sites, further proved the angiogenesis-promoting function of HA-g-TEMPO. More interestingly, wound sites demonstrated an exciting regenerative healing effect which was characterized by marked skin appendages as well as reduced scarring. Therefore, this strategy showed a promising future that could be considered as a reliable and effective method to cutaneous wound healing.
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