Polyphenol and Cu2+ surface-modified chitin sponge synergizes with antibacterial, antioxidant and pro-vascularization activities for effective scarless regeneration of burned skin

• PAs-Cu 2+ modified chitin sponges could catalyze S-nitrosothiols to generate NO. • The sponges with antioxidant properties could protect cells from ROS injury. • The sponges exhibited antibacterial and pro-vascularization properties. • The sponges could accelerate wound healing and inhibit scar formation. Bacterial overgrowth and high oxidative stress often lead to burn wound infection, hyper-inflammation, and slowed wound healing, eventually causing scar formation. Wound dressings synergized with antibacterial, antioxidant, and pro-vascularization activities can effectively promote wound healing and inhibit scars formation. Herein, chitin sponge consisted of chitin fibers was modified by the coating of proanthocyanidins (PAs) – Cu 2+ for effective scarless skin regeneration in a burn injury. The physicochemical characteristics indicated that PAs and Cu 2+ successfully modified chitin sponges by the coordination between PAs and Cu 2+ . For one thing, PAs improved the antioxidant performance of sponges, and for another, with the help of PAs, Cu 2+ effectively catalyzed S-nitrosothiols (RSNOs) to continuously generate nitric oxide (NO) in vitro/vivo for improving the inhibition of microorganisms and pro-vascularization activities. Also, Ch/PAs-Cu promoted proliferation of human umbilical vein endothelial cells (HUVECs) and rat fibroblasts (NIH-3T3), and the expression of angiogenic-related cytokines VEGF, eNOS, FGF, and MMP9. In animal experiments, Ch/PAs-Cu inhibited the accumulation of macrophages and neutrophils to regulate wound inflammation while up-regulating the expression of CD31 and α-SMA cytokines to promote angiogenesis. Ultimately, it promoted wound healing and inhibited scar formation. Therefore, Ch/PAs-Cu may be a promising dressing for the scarless repair of burned skin.