Subvacuum environment-enhanced cell migration promotes wound healing without increasing hypertrophic scars caused by excessive cell proliferation.

Cell migration and proliferation are conducive to wound healing; however, regulating cell proliferation remains challenging, and excessive proliferation is an important cause of scar hyperplasia. Here, we aimed to explore how a subvacuum environment promotes wound epithelisation without affecting scar hyperplasia. Human immortalized keratinocyte cells and human skin fibroblasts were cultured under subvacuum conditions (1/10 atmospheric pressure), and changes in cell proliferation and migration, target protein content, calcium influx, and cytoskeleton and membrane fluidity were observed. Mechanical calcium (Ca2+ ) channel blockers were used to prevent Ca2+ influx for reverse validation. A rat wound model was used to elucidate the mechanism of the subvacuum dressing in promoting healing. The subvacuum environment was observed to promote cell migration without affecting cell proliferation; intracellular Ca2+ concentrations and PI3K, p-PI3K, AKT1, p-AKT 1 levels increased significantly. The cytoskeleton was depolymerized, pseudopodia were reduced or absent, and membrane fluidity increased. The use of Ca2+ channel blockers weakened or eliminated these changes. Animal experiments confirmed these phenomena and demonstrated that subvacuum dressings can effectively promote wound epithelisation. Our study demonstrates that the use of subvacuum dressings can enhance cell migration without affecting cell proliferation, promote wound healing, and decrease the probability of scar hyperplasia.

Targeted release of stromal cell-derived factor-1α by reactive oxygen species-sensitive nanoparticles results in bone marrow stromal cell chemotaxis and homing, and repair of vascular injury caused by electrical burns.

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.