Abstract
Rapid repair of vascular injury is an important prognostic factor for electrical burns. This repair is achieved mainly via stromal cell-derived factor (SDF)-1α promoting the mobilization, chemotaxis, homing, and targeted differentiation of bone marrow mesenchymal stem cells (BMSCs) into endothelial cells. Forming a concentration gradient from the site of local damage in the circulation is essential to the role of SDF-1α. In a previous study, we developed reactive oxygen species (ROS)-sensitive PPADT nanoparticles containing SDF-1α that could degrade in response to high concentration of ROS in tissue lesions, achieving the goal of targeted SDF-1α release. In the current study, a rat vascular injury model of electrical burns was used to evaluate the effects of targeted release of SDF-1α using PPADT nanoparticles on the chemotaxis of BMSCs and the repair of vascular injury. Continuous exposure to 220 V for 6 s could damage rat vascular endothelial cells, strip off the inner layer, significantly elevate the local level of ROS, and decrease the level of SDF-1α. After injection of Cy5-labeled SDF-1α-PPADT nanoparticles, the distribution of Cy5 fluorescence suggested that SDF-1α was distributed primarily at the injury site, and the local SDF-1α levels increased significantly. Seven days after injury with nanoparticles injection, aggregation of exogenous green fluorescent protein-labeled BMSCs at the injury site was observed. Ten days after injury, the endothelial cell arrangement was better organized and continuous, with relatively intact vascular morphology and more blood vessels. These results showed that SDF-1α-PPADT nanoparticles targeted the SDF-1α release at the site of injury, directing BMSC chemotaxis and homing, thereby promoting vascular repair in response to electrical burns.
Highlights
Electrical burns are unique accidents in modern industrial society
In the group treated with only electrical burns, and the group injected with stromal cell-derived factor (SDF)-1α, GFP-bone marrow mesenchymal stem cells (BMSCs) were not detected (Fig 6). These results suggested that SDF-1α-PPADT nanoparticles can promote BMSCs homing to the injury site, indicative of directed chemotaxis
In the group treated with only simple electrical burns, and the group injected with SDF-1α, the inner layer of the blood vessels was detached, and parts of the lumen were occluded (Fig 7B, arrow). These results suggested that injection of SDF-1α-PPADT nanoparticles promoted vascular repair caused by electrical burns
Summary
Electrical burns are unique accidents in modern industrial society. Their incidence is not high, the damage is three dimensional with sandwich-like and progressive necrosis characteristics, resulting in serious damage in local tissues. Blood is a good conductor of electricity. After an electric current enters the body, it passes through blood causing blood vessel damage. Tissue ischemic and hypoxic injury resulting from vascular damage is an important reason for the progressive necrosis of electrical burns. There is no clinical treatment effective for reducing vascular injury or promoting vascular repair. How to induce the rapid repair of local blood vessels caused by electrical burns is important in reducing tissue necrosis and improving the prognosis
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