Wound repair and regeneration : official publication of the Wound Healing Society [and] the European Tissue Repair Society
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Scar research is challenging because rodents do not naturally form excessive scars, and burn depth, size, and location cannot be controlled in human longitudinal studies. The female, red Duroc pig model has been shown to form robust scars with biological and anatomical similarities to human hypertrophic scars. To more closely mimic the mode of injury, recreate the complex chemical milieu of the burn wound environment and enhance scar development, an animal model of excessive burn-induced scarring was developed and compared with the more commonly used model, which involves excisional wounds created via dermatome. ⋯ In addition, transforming growth factor-beta 1 was significantly up-regulated in the burn group vs. the ∼1.5 mm deep dermatome group at all time points, and expression remained significantly elevated vs. both dermatome groups at day 150. Compared with scars from dermatome wounds, the burn scar model described here demonstrates greater similarity to human hypertrophic scar. Thus, this burn scar model may provide an improved platform for studying the pathophysiology of burn-related hypertrophic scarring, investigating current anti-scar therapies, and development of new strategies with greater clinical benefit.
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Burn-induced tissue loss is partly related to secondary expansion of necrosis into vital dermis neighboring the initial burn injury. An important factor herein is the severe loss of perfusion of the burn wound, probably caused by microvascular damage induced by the intense local inflammatory responses as well as burn-induced hypercoagulation. We hypothesize that the formation of neutrophilic extracellular traps (NETs) play an important role in this. ⋯ In pigs, a significant increase in intravascular thrombi and TF expression was found over time up to 60 days postburn, that in majority coincided with NETs too. Also in eschar of burn wound patients, a significant increase in intravascular thrombi was noted, that in majority coincided with NETs, already 0.5 days postburn and remained elevated up to 46 days postburn. This study shows the presence of NETosis in microcirculatory thrombosis of burn wounds and a switch in the microcirculatory endothelium toward a procoagulant phenotype.
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C-X-C chemokine receptor type 4 (CXCR4) is an alpha-chemokine receptor specific for stromal cell-derived factor 1 (SDF-1 also called CXCL12). The antagonist of CXCR4 can mobilize CD34+ cells and hematopoietic stem cells from bone marrow within several hours, and it has an efficacy on diabetes ulcer through acting on the SDF-1/CXCR4 axis. In this study, we investigated for the first time whether the antagonist of CXCR4 (Plerixafor/AMD3100) delivered on acellular dermal matrix (ADM) may accelerate diabetes-impaired wound healing. ⋯ Full-thickness cutaneous wound in streptozotocin (STZ)-induced diabetic mice were treated with ADM, AMD3100, or ADM-AMD3100. 21 days after treatment, wound closure in ADM-AMD3100-treated mice was more complete than ADM group and AMD3100 group, and it was accompanied by thicker collagen formation. Correspondingly, diabetic mice treated with ADM-AMD3100 demonstrated prominent neovascularization (higher capillary density and vascular smooth muscle actin), which were accompanied by up-regulated mRNA levels of SDF-1 and enhanced migration of CXCR4 in the granulation tissue. Our results demonstrate that ADM scaffold provide perfect niche for loading AMD3100 and ADM-AMD3100 is a promising method for diabetic wound healing mainly by increasing expression of SDF-1 and enhancing migration of CXCR4-positive cells.
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Complex stalled wounds feature an alkaline milieu that favors tissue destruction and microbial growth. The presence of bacteria in turn perpetuates the inflammatory response. However, only limited knowledge exists of pH dependency on the antibacterial efficacy of polyhexamethylene biguanide (PHMB) or the influence of surfactants or delivery vehicle used in antiseptic formulations. ⋯ Undecylenamidopropyl betaine was found to lower the antimicrobial activity of polihexanide in the co-culture system, while macrogolum and the biocellulose increased polihexanide efficiency to reduce Staphylococcus aureus especially in the presence of serum. The increasing antibacterial efficacy of PHMB with rising pH was not altered by undecylenamidopropyl betaine, macrogolum, or the biocellulose. The results suggest that application of PHMB with macrogolum or by delivery through a biocellulose dressing might be advantageous for management of wound infections.
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The disparity between ideal evidence from randomized controlled trials and real-world evidence in medical research has prompted the United States Food and Drug Administration to consider the use of real-world data to better understand safety and effectiveness of new devices for a broader patient population and to prioritize real-world data in regulatory decision making. As the healthcare system transitions from volume- to value-based care, there is a growing need to harness the power of real-world data to change the paradigm for wound care clinical research and enable more generalizable clinical trials. ⋯ The common definitional framework of the purpose-built electronic health record and the 21 wound-specific quality measures help to standardize the potential sources of bias in real-world data, making the consortium data useful for comparative effectiveness research. This consortium can transform wound care clinical research and raise the standards of care, while helping physicians achieve success with the Merit-Based Incentive Payment System.