Targeted Reprogramming of Macrophages by Nanozyme for Accelerated Wound Healing.

Abstract

Wound healing is a huge challenge for medicine that enhances tissue regeneration and macrophage reprogramming. However, current therapies do not coordinate tissue regeneration and macrophage recombination, leading to an increase in chronic wound disability. To address these challenges, we developed a self-assembled polyvinylpyrrolidone-modified zirconium Prussian blue (PB) (PVP/Zr-PB) nanomaterial through one-step hydrothermal synthesis. This engineered platform synergistically promoted wound closure by combining targeted reactive oxygen species (ROS) scavenging with the establishment of a pro-regenerative immune microenvironment that enhanced tissue repair and macrophage polarization. Key findings demonstrated PVP/Zr-PB's significantly improved ROS-scavenging capabilities over PVP/PB across all tested enzymes. At a 150 ng/mL concentration, the material achieved >85% ROS clearance efficiency. In vitro, PVP/Zr-PB promoted M2 macrophage polarization and ameliorated mitochondrial dysfunction. Correspondingly, in vivo experiments demonstrated significantly enhanced wound closure rates and tissue contraction. Masson's trichrome staining revealed significantly increased capillary formation, orderly deposition of collagen fibers, and marked epithelialization in the PVP/Zr-PB treatment group compared to controls. PVP/Zr-PB treatment significantly reduced expression levels of extracellular matrix components, decreasing CoL I and MMP1 by 90%, and CoL III by 60% (immunohistochemistry). The result of proteomics analysis suggested that PVP/Zr-PB can mediate immunosuppression and thus promote wound healing. These results demonstrate PVP/Zr-PB's ability to remodel the wound microenvironment, suggesting therapeutic potential for oxidative stress-associated pathologies.