CaO2–Cu2O micromotors accelerate infected wound healing through antibacterial functions, hemostasis, improved cell migration, and inflammatory regulation

Abstract

During the wound tissue healing process, the relatively weak driving forces of tissue barriers and concentration gradients lead to a slow and inefficient penetration of bioactive substances into the wound area, consequently showing an impact on the effectiveness of deep wound healing. To overcome these challenges, we constructed biocompatible CaO₂–Cu₂O “micromotors”. These micromotors reacted with the fluids at the wound site, releasing oxygen bubbles and propelling particles deep into the wound tissue. In vitro experimental results revealed that these micromotors not only exhibited antibacterial and hemostatic functions but also facilitated the migration of dermal fibroblasts and vascular endothelial cells, while modulating the inflammatory microenvironment. A methicillin-resistant Staphylococcus aureus infected full-thickness-wound model was created in rats, in which CaO₂–Cu₂O micromotors markedly expedited the wound healing process. Specifically, CaO₂–Cu₂O provided a sterile microenvironment for wounds and increased the amounts of M1-type macrophages during infection and inflammation. During the proliferation and remodeling stages, the amount of M1 macrophages gradually decreased, while the amount of M2 macrophages increased, and CaO₂–Cu₂O did not prolong the inflammatory period. Furthermore, the introduction of a regenerated silk fibroin (RSF) film on the wound surface successfully enhanced the therapeutic effects of CaO₂–Cu₂O against the infected wound. The combined application of oxygen-producing CaO₂–Cu₂O micromotors and a RSF film demonstrates significant therapeutic potential and emerges as a promising candidate for the treatment of infected wounds.