Lung Surfactant Accelerates Skin Wound Healing: A Translational Study with a Randomized Clinical Phase I Study
Lung Surfactant Accelerates Skin Wound Healing: A Translational Study with a Randomized Clinical Phase I Study
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DOI：
10.1038/s41598-020-59394-5
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发表时间：
2020-02-13
影响因子：
4.6
通讯作者：
Timm, Juergen
中科院分区：
文献类型：
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作者：
Mirastschijski, Ursula;Schwab, Igor;Timm, Juergen
肺表面活性剂用于降低早产儿肺泡表面张力以缓解呼吸。具有表面活性蛋白的磷脂膜调节肺泡巨噬细胞的活性并减少炎症。皮肤伤口异常愈合的特征是持续性炎症。该研究的目的是调查肺表面活性物质是否可以促进伤口愈合。临床前伤口模型，例如小鼠中的细胞划痕测定和全层切除伤口，以及使用抽吸水泡模型在健康人类志愿者中进行的随机I期临床试验，用于研究市售牛肺表面活性剂对皮肤伤口修复的作用。肺表面活性物质以浓度依赖性方式增加角质形成细胞的迁移，对成纤维细胞无影响。在小鼠伤口中发现促炎基因和促纤维化基因的表达水平显著降低。由于临床前实验中的这些有益作用，启动了临床I期研究，以监测表面活性剂局部应用于人体伤口和正常皮肤时的安全性和耐受性。未观察到不良反应。与对照组相比，表面活性剂的表皮下伤口愈合明显更快。我们的研究提供了肺表面活性剂作为慢性皮肤伤口的创新治疗的强有力的候选者，并作为治疗烧伤伤口的添加剂，以减少炎症和防止过度瘢痕形成。
Lung surfactants are used for reducing alveolar surface tension in preterm infants to ease breathing. Phospholipid films with surfactant proteins regulate the activity of alveolar macrophages and reduce inflammation. Aberrant skin wound healing is characterized by persistent inflammation. The aim of the study was to investigate if lung surfactant can promote wound healing. Preclinical wound models, e.g. cell scratch assays and full-thickness excisional wounds in mice, and a randomized, phase I clinical trial in healthy human volunteers using a suction blister model were used to study the effect of the commercially available bovine lung surfactant on skin wound repair. Lung surfactant increased migration of keratinocytes in a concentration-dependent manner with no effect on fibroblasts. Significantly reduced expression levels were found for pro-inflammatory and pro-fibrotic genes in murine wounds. Because of these beneficial effects in preclinical experiments, a clinical phase I study was initiated to monitor safety and tolerability of surfactant when applied topically onto human wounds and normal skin. No adverse effects were observed. Subepidermal wounds healed significantly faster with surfactant compared to control. Our study provides lung surfactant as a strong candidate for innovative treatment of chronic skin wounds and as additive for treatment of burn wounds to reduce inflammation and prevent excessive scarring.