Refractory wound healing is one of the most common complications of diabetes. Excessive production of reactive oxygen species (ROS) can cause chronic inflammation and thus impair cutaneous wound healing. Scavenging these ROS in wound dressing may offer effective treatment for chronic wounds. Here, a nanocomposite hydrogel based on alginate and positively charged Eudragit nanoparticles containing edaravone, an efficient free radical scavenger, was developed for maximal ROS sequestration. Eudragit nanoparticles enhanced edaravone solubility and stability breaking the limitations in application. Furthermore, loading these Eudragit nanoparticles into an alginate hydrogel increased the protection and sustained the release of edaravone. The nanocomposite hydrogel is shown to promote wound healing in a dose-dependent way. A low dose of edaravone-loaded nanocomposite hydrogel accelerated wound healing in diabetic mice. On the contrary, a high dose of edaravone might hamper the healing. Those results indicated the dual role of ROS in chronic wounds. In addition, the discovery of this work pointed out that dose could be the key factor limiting the translational application of antioxidants in wound healing.

S-Nitrosothiolated AIEgens have been demonstrated to monitor NO release and reverse chemi-resistance.

SignificanceCell volume serves as a macroscopic indicator of cellular metabolism, growth, and signal transduction. Understanding how cell volume varies across macrophage phenotypes is essential for interpreting their functional states and activation processes.AimWe present a label-free, noninvasive method for 3D morphological characterization and volume quantification of macrophages and apply it to monitor volume variations during their biological behaviors.ApproachWe employed a home-made off-axis digital holographic microscopy (DHM) system based on a Mach–Zehnder interferometric configuration to reconstruct the 3D morphology of cells. Using the mathematical relationship between the phase map and the cell thickness, we further calculated their cellular volume.ResultsOur measurements show that M0 macrophages have a nearly spherical morphology with a volume of 970.54±153.15 μm3. M1 macrophages exhibit a flattened, pancake-like morphology with pseudopodia, with a significantly larger volume of 3822.00±437.45 μm3. M2 macrophages present a morphology resembling that of M0 cells but with a volume of 2743.10±254.67 μm3. It indicates that the cell volume might be a potential parameter to distinguish different polarized macrophages. In addition, we successfully monitored the volume changes of macrophages during cell death, cell division, and the polarization process from M0 to M1. The cell-death process behaved as expected, with the cell volume continuously decreasing and eventually reaching a plateau. The division event we observed occurred together with cell death; during division, the total volume of the cell cluster increased sharply and then gradually decreased as cell death progressed. During the 8-h M0-to-M1 polarization process, two phases of gradual volume increase and two phases of rapid volume increase were observed. In the early stage (0 to 2 h), M0 macrophages were likely not fully activated, showing only mild volume changes but still exhibiting an increasing trend. At 6 to 8 h, the cells undergo a sharp increase in volume, reflecting their full activation and transition toward the M1 phenotype.ConclusionsWe demonstrate that DHM offers a powerful label-free strategy for quantifying macrophage volume and capturing the volume dynamic. It might be a potential approach for a macroscopic characterization to observe intracellular activities.