Abstract Regenerable nanozymes with high catalytic stability and sustainability are promising substitutes for naturally-occurring enzymes but are limited by insufficient and non-selective catalytic activities. Herein, we developed single-atom nanozymes of RhN 4 , VN 4 , and Fe-Cu-N 6 with catalytic activities surpassing natural enzymes. Notably, Rh/VN 4 preferably forms an Rh/V-O-N 4 active center to decrease reaction energy barriers and mediates a “two-sided oxygen-linked” reaction path, showing 4 and 5-fold higher affinities in peroxidase-like activity than the FeN 4 and natural horseradish peroxidase. Furthermore, RhN 4 presents a 20-fold improved affinity in the catalase-like activity compared to the natural catalase; Fe-Cu-N 6 displays selectivity towards the superoxide dismutase-like activity; VN 4 favors a 7-fold higher glutathione peroxidase-like activity than the natural glutathione peroxidase. Bioactive sutures with Rh/VN 4 show recyclable catalytic features without apparent decay in 1 month and accelerate the scalp healing from brain trauma by promoting the vascular endothelial growth factor, regulating the immune cells like macrophages, and diminishing inflammation.