Complex dermal wounds represent major medical and financial burdens, especially in the context of comorbidities such as diabetes, infection and advanced age. New approaches to accelerate and improve, or “fine tune” the healing process, so as to improve the quality of cutaneous wound healing and management, are the focus of intense investigation. Here, we investigate the topical application of a recombinant immune modulating protein which inhibits the interactions of chemokines with glycosaminoglycans, reducing damaging or excess inflammation responses in a splinted full-thickness excisional wound model in mice. M-T7 is a 37 kDa-secreted, virus-derived glycoprotein that has demonstrated therapeutic efficacy in numerous animal models of inflammatory immunopathology. Topical treatment with recombinant M-T7 significantly accelerated wound healing when compared to saline treatment alone. Healed wounds exhibited properties of improved tissue remodeling, as determined by collagen maturation. M-T7 treatment accelerated the rate of peri-wound angiogenesis in the healing wounds with increased levels of TNF, VEGF and CD31. The immune cell response after M-T7 treatment was associated with a retention of CCL2 levels, and increased abundances of arginase-1-expressing M2 macrophages and CD4 T cells. Thus, topical treatment with recombinant M-T7 promotes a pro-resolution environment in healing wounds, and has potential as a novel treatment approach for cutaneous tissue repair.

中文翻译：

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重组黏液瘤病毒衍生的免疫调节剂M-T7加速皮肤伤口愈合并改善组织重塑

复杂的皮肤伤口代表主要的医疗和财务负担，尤其是在合并症如糖尿病，感染和高龄的情况下。旨在加快和改善或“微调”愈合过程，从而改善皮肤伤口愈合和管理质量的新方法是广泛研究的重点。在这里，我们调查重组免疫调节蛋白的局部应用，该蛋白可抑制趋化因子与糖胺聚糖的相互作用，减少夹板的全厚度切除伤口模型中的伤害性或过度炎症反应。M-T7是一种分泌37 kDa的病毒衍生糖蛋白，已在多种炎症免疫病理动物模型中显示出治疗功效。与单独的盐水治疗相比，重组M-T7的局部治疗可显着加速伤口愈合。愈合的伤口表现出改善的组织重塑特性，这取决于胶原蛋白的成熟程度。M-T7处理通过增加TNF，VEGF和CD31的水平来加速伤口愈合过程中伤口周围血管新生的速度。M-T7处理后的免疫细胞应答与CCL2水平的保留，表达精氨酸酶1的M2巨噬细胞和CD4 T细胞的丰度增加有关。因此，用重组M-T7的局部治疗促进了伤口愈合中的前拆分环境，并且具有作为皮肤组织修复的新治疗方法的潜力。M-T7处理通过增加TNF，VEGF和CD31的水平来加速伤口愈合过程中伤口周围血管新生的速度。M-T7处理后的免疫细胞应答与CCL2水平的保留，表达精氨酸酶1的M2巨噬细胞和CD4 T细胞的丰度增加有关。因此，用重组M-T7的局部治疗促进了伤口愈合中的前拆分环境，并且具有作为皮肤组织修复的新治疗方法的潜力。M-T7处理通过增加TNF，VEGF和CD31的水平来加速伤口愈合过程中伤口周围血管新生的速度。M-T7处理后的免疫细胞应答与CCL2水平的保留，表达精氨酸酶1的M2巨噬细胞和CD4 T细胞的丰度增加有关。因此，用重组M-T7的局部治疗促进了伤口愈合中的前拆分环境，并且具有作为皮肤组织修复的新治疗方法的潜力。