Characteristics of Serum Exosomes after Burn Injury and Dermal Fibroblast Regulation by Exosomes In Vitro.

(1) Background: Exosomes (EXOs) have been considered a new target thought to be involved in and treat wound healing. More research is needed to fully understand EXO characteristics and the mechanisms of EXO-mediated wound healing, especially wound healing after burn injury. (2) Methods: All EXOs were isolated from 85 serum samples of 29 burn patients and 13 healthy individuals. We characterized the EXOs for morphology and density, serum concentration, protein level, marker expression, size distribution, and cytokine content. After a confirmation of EXO uptake by dermal fibroblasts, we also explored the functional regulation of primary human normal skin and hypertrophic scar fibroblast cell lines by the EXOs in vitro, including cell proliferation and apoptosis. (3) Results: EXOs dynamically changed their morphology, density, size, and cytokine level during wound healing in burn patients, which were correlated with burn severity and the stages of wound healing. EXOs both from burn patients and healthy individuals stimulated dermal fibroblast proliferation and apoptosis. (4) Conclusions: EXO features may be important signals that influence wound healing after burn injury; however, to understand the mechanisms by which EXOs regulates the fibroblasts in healing wounds, further studies will be required.

The dynamic changes of monocytes and cytokines during wound healing post-burn injury.

BACKGROUND: Burn injury is a sudden and traumatic injury that affects a large part of the population worldwide, who are placed at high risk of developing hypertrophic scars (HTS). HTS are a fibrotic scar resulting in painful contracted and raised scarring, affecting mobility in joints and work life, as well as cosmetically. The aim of this research was to enhance our understanding of the systematic response of monocytes and cytokines in wound healing after burn injury, in order to develop novel approaches to prevention and treatment of HTS. METHODS: Twenty-seven burn patients and thirteen healthy individuals were recruited in this study. Burn patients were stratified by burn total body surface area (TBSA). Peripheral blood samples were taken post-burn injury. Serum and peripheral blood mononuclear cells (PBMCs) were separated from the blood samples. This research investigated cytokines IL-6, IL-8, IL1RA, IL-10, and chemokine pathways SDF-1/CXCR4, MCP-1/CCR2, RANTES/CCR5 during the wound healing process in burn patients with varying severity of injuries by using enzyme-linked immunosorbent assays. PBMCs were stained for monocytes and the chemokine receptors by flow cytometry. Statistical analysis was done by one-way ANOVA with a Tukey correction, and regression analysis was performed using Pearson's Correlation analysis. RESULTS: The CD14+ CD16- monocyte subpopulation is larger in patients who developed HTS at 4-7 days. The CD14+ CD16+ monocyte subpopulation is smaller in the first week of injury, where it is similar after 8 days. Burn injury increased CXCR4, CCR2, and CCR5 expressions in CD14+ CD16+ monocytes. Increases in MCP-1 at 0-3 days after burn injury was positively correlated with burn severity. IL-6, IL-8, RANTES, and MCP-1 significantly increased with increasing burn severity. CONCLUSIONS: Monocytes and their chemokine receptors, as well as systemic levels of cytokines in wound healing of burn patients and scar development will require ongoing assessment to enhance our understanding of the abnormal wound healing after burn injury.

Molecular Features of Hypertrophic Scars After Thermal Injury: Is There a Biologic Basis for Laser Therapy?

Significance: Hypertrophic scars (HTS) and keloids are common after thermal injuries and other trauma to deep regions of dermis of the skin. These abnormal scars can cause contractures and the thick masses of scar tissue that result in functional and cosmetic impairment. Management of these dermal fibrotic conditions includes a wide range of medical and surgical treatments, which can be time consuming, only partially effective, and often uncomfortable for patients. Recent Advances: The molecular pathophysiology of HTS has become more understood over the past two decades, where thermal injury to the reticular dermis results in an inflammatory response, fibrogenic growth factor release, and the formation of a dermal scar with increased collagen and proteoglycan composition in an abnormal morphology. Lasers are becoming a widely used form of treatment for these types of scars; however, the evidence for the beneficial effects of laser treatments and the understanding of their mechanism of action are still evolving. Critical Issues: Paradoxically, laser delivery of thermal energy to the skin is suggested to improve scar remodeling and wound healing, yet HTS is a well-recognized complication of excessive thermal energy delivered by laser treatments. This review aims to examine the current evidence for the use of lasers for HTS, and to investigate the molecular mechanisms where re-injury of a burn scar from laser treatment could result in overall improvements in scar quality. Future Directions: Improved design of clinical trials for the treatment of scarring in the future will evolve from new methodology and models of HTS in animals and humans.