Abstract
Reactive oxygen species (ROS) play a dual role in wound healing. They act as crucial signaling molecules and antimicrobial agents when present at moderate levels. However, excessive levels of ROS can hinder the healing process for individuals with diabetes. As a result, targeting ROS levels to maintain redox balance has become a promising strategy for improving wound recovery. Currently, no biomaterials have been reported to simultaneously up-regulate and down-regulate ROS to achieve broad-spectrum antibacterial and antioxidant properties. Inspired by the site-dependent effect of nanomaterials, a micron-sized ferroferric oxide (Fe(3)O(4))/MXene (FM) heterojunction is synthesized using a hydrothermal method. The FM heterojunction could scavenge extracellular ROS by activating catalase (CAT)-like and superoxide dismutase (SOD)-like nanozyme activities. Meanwhile, FM heterojunction could release ferric ions and ferrous ions by defect engineering to induce bacterial ferroptosis, up-regulating intercellular ROS, and lipid peroxidation. For applications in vivo, FM heterojunction is incorporated into the tips of gelatin methacryloyl (GelMA)-based microneedle (termed as GFM microneedle) using a two-step casting technique. The results showed that GFM microneedle combined with photothermal therapy could improve S. aureus-infected skin regeneration in diabetic rats. The effectiveness and safety of GFM microneedle are not less favorable than that of a commercial wound dressing. This study provides a proof-of-concept for heterojunction-mediated regenerative medicine via a site-dependent ROS-targeting strategy.