Trehalose promotes functional recovery of keratinocytes under oxidative stress and wound healing via ATG5/ATG7.

Wounds are in a stressed state, which precludes healing. Trehalose is a stress metabolite that protects cells under stress. Here, we explored whether trehalose reduces stress-induced wound tissue damage. A stress model was prepared by exposing human keratinocytes to hydrogen peroxide (H2O2), followed by trehalose treatment. Trehalose effects on expression of the autophagy-related proteins ATG5 and ATG7 and cell proliferation and migration were evaluated. For in vivo verification, a wound model was established in Sprague-Dawley rats, to measure the effects of trehalose wound-healing rate and reactive oxygen species (ROS) content. Histological changes during wound healing and trehalose's effects on ATG5 and ATG7 expression, necrosis, and apoptosis were examined·H2O2 stress increased ATG5 and ATG7 expression in vitro, but this was insufficient to prevent stress-induced damage. Trehalose further increased ATG5/ATG7 levels, which restored proliferation and increased migration by depolymerizing the cytoskeleton. However, trehalose did not exert these effects after ATG5 and ATG7 knockout. In vivo, the ROS content was higher in the wound tissue than in normal skin. Trehalose increased ATG5/ATG7 expression in wound tissue keratinocytes, reduced necrosis, depolymerized the cytoskeleton, and promoted cell migration, thereby promoting wound healing.

Synergistic Effects of Quercetin-Modified Silicone Gel Sheet in Scar Treatment.

Both silicone gel and quercetin are effective in scar treatment but have different action mechanisms. Quercetin is mainly applied in the gel form and can lead to poor adhesion of silicone gel sheet; therefore, they cannot be combined in clinical use. In this study, a silicone gel sheet that releases quercetin in a sustained manner for 48 hours was successfully developed. Four round scars (Ø: 1 cm) were made in the ears of New Zealand albino rabbits (n = 10). After scar healing, the rabbits were divided into four groups: blank control group with no treatment, silicone gel sheet group with dressing change every 2 days, quercetin group with dressing change three times daily, and combination treatment group with dressing change every 2 days. Scar assessment was performed 3 months later. Transepidermal water loss showed no difference between the combination treatment group and the silicone gel sheet group, but was lower than that in the quercetin group and the blank control group. Immunohistochemistry of CD 31 and proliferating cell nuclear antigen showed the following results: combination treatment group < silicone gel sheet group = quercetin group < blank control group. Polymerase chain reaction results showed that the expression of type-I and type-III collagen in the combination treatment group and the quercetin group was significantly lower than that in the other two groups. Thus, quercetin-modified silicone gel sheet combines the advantages of the two treatments and is more effective at inhibiting cell proliferation in scar tissue than either of the two treatments alone.

Development of a PHMB hydrogel-modified wound scaffold dressing with antibacterial activity.

Current wound scaffold dressing constructs can facilitate wound healing but do not exhibit antibacterial activity, resulting in high infection rates. We aimed to endow wound scaffold dressing with anti-infective ability by polyhexamethylenebiguanide (PHMB). We prepared PHMB hydrogel at varying concentrations (0.25%, 0.5%, 1%, 2%) and assessed release and cytotoxicity. PHMB hydrogel was added to the wound scaffold dressing to generate a PHMB hydrogel-modified wound scaffold dressing. Wound healing and infection prevention were evaluated using a full-thickness skin defect model in rats. In vitro, the hydrogel PHMB release time positively correlated with PHMB concentration, with 1% allowing sufficiently long release time to encompass the high-incidence period (3-5 days) of infection following wound scaffold dressing implantation. Implantation of 1% PHMB hydrogel into the skin did not cause adverse responses. in vitro cytotoxicity assays showed the PHMB hydrogel-modified wound scaffold dressing did not significantly affect proliferation of fibroblasts or vascular endothelial cells, 99.90% vs 99.84% for fibroblasts and 100.21% vs 99.28% for vascular endothelial cells at 21 days. Transplantation of PHMB hydrogel-modified wound scaffold dressing/unmodified wound scaffold dressing on the non-infected wounds of rats yielded no significant difference in relative vascularization rate, 47.40 vs 50.87 per view at 21 days, whereas bacterial content of the wound tissue in the PHMB hydrogel-modified wound scaffold dressing group was significantly lower than the unmodified wound scaffold dressing group, (1.80 ± 0.35) × 103 vs (9.34 ± 0.45) × 103 at 14 days. Prevalence of persistent wound infection in the rats receiving PHMB hydrogel-modified wound scaffold dressing transplantation onto infected wounds was significantly lower than the unmodified wound scaffold dressing group, 30% vs 100%. PHMB hydrogel-modified wound scaffold dressing exhibited suitable antibacterial ability, and its biological activity did not significantly differ from that of the unmodified wound scaffold dressing, thereby allowing it to effectively prevent infection following wound scaffold dressing implantation.

Burn-Related Dysregulation of Inflammation and Immunity in Experimental and Clinical Studies.

The purpose of this study was to evaluate burn-related variations of inflammation and immunity. Fifty-five mice were divided randomly into sham burn and burn groups. Eighty-seven hospitalized burn patients were also reviewed. In mice, neutrophils and monocytes were elevated significantly on post burn day (PBD 1). Lymphocytes were reduced on PBDs 1 and 3. Levels of serum tumor necrosis factor-α and interleukin-6 were highest on PBD 1. Interleukin-1ß levels were the highest on PBD 3. On PBD 3, CD4CD25T regulatory cells/CD4 cells in spleen were higher. On PBDs 1, 3, 7, and 14, percentage of splenic dendritic cells were significantly lower than the sham burn group. In patients, neutrophils and monocytes were significantly elevated on PBD 1. Levels declined but remained elevated at most days to PBD 7. Lymphocytes in burn groups 1 and 2 were reduced on PBDs 1 and 3, respectively. Our results exhibited that severe burn injury initiated a hyperinflammatory response and immunosuppression. PBDs 1 to 3 were important for changes in inflammation and immunosuppression.