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.

Tetrahedral framework nucleic acids promote diabetic wound healing via the Wnt signalling pathway.

OBJECTIVES: To determine the therapeutic effect of tetrahedral framework nucleic acids (tFNAs) on diabetic wound healing and the underlying mechanism. MATERIALS AND METHODS: The tFNAs were characterized by polyacrylamide gel electrophoresis (PAGE), atomic force microscopy (AFM), transmission electron microscopy (TEM), dynamic light scattering (DLS) and zeta potential assays. Cell Counting Kit-8 (CCK-8) and migration assays were performed to evaluate the effects of tFNAs on cellular proliferation and migration. Quantitative polymerase chain reaction (Q-PCR) and enzyme-linked immunosorbent assay (ELISA) were used to detect the effect of tFNAs on growth factors. The function and role of tFNAs in diabetic wound healing were investigated using diabetic wound models, histological analyses and western blotting. RESULTS: Cellular proliferation and migration were enhanced after treatment with tFNAs in a high-glucose environment. The expression of growth factors was also facilitated by tFNAs in vitro. During in vivo experiments, tFNAs accelerated the healing process in diabetic wounds and promoted the regeneration of the epidermis, capillaries and collagen. Moreover, tFNAs increased the secretion of growth factors and activated the Wnt pathway in diabetic wounds. CONCLUSIONS: This study indicates that tFNAs can accelerate diabetic wound healing and have potential for the treatment of diabetic wounds.

A recombinant human collagen hydrogel for the treatment of partial-thickness burns: A prospective, self-controlled clinical study.

INTRODUCTION: Allogeneic and xenogeneic skin are recognized as the best coverings for skin burn wounds, but currently face a supply shortage. To solve this problem, our research group developed a standardized manufactured hydrogel dressing based on a new type of highly bioactive recombinant human collagen. STUDY DESIGN: Prospective self-controlled trial. OBJECTIVE: To evaluate the efficacy and safety of recombinant human collagen hydrogel in the treatment of partial burn wounds to the skin compared to those of xenogeneic skin. METHODS: This study included twenty-one patients admitted to Shanghai Changhai Hospital within 48 h after receiving partial-thickness skin burns. The wounds were symmetrically separated along the axis and treated with recombinant human collagen hydrogel (RHCH) or a human-CTLA4-Ig gene-transferred pig skin xenotransplant. The condition of the wound surfaces was recorded on days 0 (of enrollment), 5, 10, 15, and 20, and bacterial drug sensitivity testing, hematuria examination, and electrocardiographic tests were conducted on days 0, 10, 20, or on the day of wound healing. RESULTS: There were no statistically significant differences in wound healing time between the two groups. The median number of days to healing was 11.00 ± 0.56 for xenogeneic skin vs. 11.00 ± 1.72 for RHCH. CONCLUSION: During the observation period, the therapeutic effect of the RHCH developed by our group on partial-thickness burn wounds was not significantly different from that of gene-transferred xenogeneic skin. Thus, our designed RHCH shows potential for clinical use to treat burn wounds on the skin.

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.

The therapeutic efficacy of Ulinastatin for rats with smoking inhalation injury.

Smoke inhalation injury represents a major cause of mortality in burn patients and is associated with a high incidence of pulmonary complications. Ulinastatin (UTI) has been widely used as a drug for patients with severe burn, sepsis, severe acute pancreatitis, and multiple organ dysfunction syndrome. In view of the critical role of inflammatory response in pathogenesis of smoke inhalation-induced lung injury and the anti-inflammatory effects of UTI, we hypothesized that treatment with UTI could lessen smoke inhalation-induced lung injury. In this study, fifty-four rats were equally randomized to three groups: Sham group (ambient air inhalation), Control group (smoke inhalation injury) and UTI treatment group (UTI treatment plus smoke inhalation injury). At sampling, bronchoalveolar lavage fluid was performed to determine total protein concentration and pro-inflammatory cytokine levels. Lung tissues were collected for the measurement of wet/dry ratio, myeloperoxidase, histopathology, hydroxyproline, collagens I and III, and western blotting. Our present work exhibited that UTI attenuated the lung histopathological alterations, improved the pulmonary function, inhibited neutrophil accumulation and mitigated pulmonary edema. In addition, UTI mitigated the inflammatory response, and further prevented the initiation of downstream inflammatory cascades: NF-κB and p-JNK. Importantly, UTI also mitigated smoke inhalation-induced pulmonary fibrosis as evidenced by Masson-Goldner trichrome staining with the content of hydroxyproline and collagens I and III. In conclusion, our data demonstrated that UTI protected rat against smoke inhalation-induced acute lung injury and the subsequent development of pulmonary fibrosis.