Accelerated Wound Healing of Tetrahedral-Framework Nucleic Acid Nanozymes with High Penetration and Antioxidant Capacity

The wound repair process usually leads to a non-functioning mass of fibrotic tissue because of the oxidative imbalance of deep tissue layers. However, how to improve the penetration of active ingredients into deeper layers and regulate oxidative imbalances to create a regenerative microenvironment still remains a challenge. In this study, we designed a novel tetrahedral-framework nucleic acid (tFNA) nanozyme that could penetrate the skin/mucosa barrier as deep as 450 μm within 24 h. We also demonstrated the protective role of tFNAs on the mitochondrial structural and functional integrity and inhibition of reactive oxygen species production to repair oxidative imbalances through ERK1/2-Nrf2-HO-1 during repair processes. It was found that the proliferative state and the migration ability of postburn cells in vitro were accelerated, and the early closure of wounds in vivo was significantly promoted. This study therefore provides a promising strategy to efficiently regulate the oxidative imbalances in the deep layers of the skin during wound healing.