A Deferoxamine-Loaded Microneedle Patch Enhances Healing of Radiation-Induced Skin Injury: Potential Involvement of Ferroptosis.

Radiation-induced skin injury (RSI) presents a significant challenge in wound care due to its complex pathophysiology, which includes increased oxidative stress, impaired angiogenesis, and delayed re-epithelialization. Transcriptomic analysis reveals significant alterations in genes associated with the ferroptosis pathway following radiation exposure. In this study, we introduce microneedles composed of silk fibroin hydrogel loaded with deferoxamine (SF+MNs+DFO) to inhibit ferroptosis. SF+MNs+DFO exhibits optimal mechanical properties and drug release kinetics. Histopathological analysis shows reduced inflammation, oxidative stress, and collagen deposition in RSI treated with SF+MNs+DFO, leading to accelerated tissue regeneration and decreased scarring. Molecular biology studies indicate that SF+MNs+DFO inhibits ferroptosis by reducing the concentration of free Fe²⁺ in the body, thereby decreasing the generation of reactive oxygen species (ROS) and lipid peroxidation. Immunofluorescence studies further confirm the increased neovascularization and reduced fibrosis in SF+MNs+DFO-treated RSI, indicating enhanced tissue repair. SF+MNs+DFO not only inhibits ferroptosis but also promotes angiogenesis and tissue regeneration, offering a promising therapeutic strategy for RSI. In conclusion, DFO-loaded SF hydrogel microneedles provide precise drug delivery, iron chelation, and improved wound healing, demonstrating an effective approach for treating RSI.