Manganese Dioxide Nanozyme-Constituted Composite Hydrogel to Scavenge Reactive Oxygen Species for Scarless Wound Healing.

Pathological skin scarring is still a major obstacle due to functional impairment and psychological diseases. Excessive reactive oxygen species (ROS) can hinder the healing of skin wound and increase the formation of scar tissues. To address this dilemma here, manganese dioxide (MnO2) nanozyme-constituted GelMA hydrogel was designed to eliminate ROS, while vascular endothelial growth factor (VEGF)-encapsulated RADA16 peptide nanofibers improved the angiogenesis responses for rapid wound healing, thus paving the way to design and orchestrate RADA16/VEGF/MnO2@GelMA composite hydrogel. With tailored physicochemical properties and favorable biocompatibility, our in vitro experiments revealed that RADA16/VEGF/MnO2@GelMA composite hydrogel enabled the controlled release of the MnO2 nanozyme to restrain excessive collagen deposition and the stimulus of VEGF to enhance vascularization. In the full-thickness skin defect rat model, this composite hydrogel significantly minimized scar formation and triggered functional neovascularization, promoting the scarless wound healing. This innovative RADA16/VEGF/MnO2@GelMA composite hydrogel-based therapeutic strategy presents an advanced approach toward scarless wound healing, holding great promise in orchestrating the synergistic effects of scar inhibition and angiogenesis promotion.