Cullen Breda, Smith Rachel, McCulloch Elaine, Silcock Derek, Morrison Libby
R&DDepartment, Johnson & Johnson Advanced Wound Care, A Division of Ethicon, Gargrave, North Yorkshire, United Kingdom.
Wound Repair Regen. 2002 Jan-Feb;10(1):16-25. doi: 10.1046/j.1524-475x.2002.10703.x.
Proteases play a critical role in many of the physiologic processes of wound repair. However, if their activity becomes uncontrolled proteases can mediate devastating tissue damage and consequently they have been implicated in chronic wound pathophysiology. Previous studies have shown that chronic wound fluid contains elevated protease levels that have deleterious effects, degrading de novo granulation tissue and endogenous biologically active proteins such as growth factors and cytokines. Therefore, we have proposed that an effective therapeutic approach for chronic wounds would be to modify this hostile environment and redress this proteolytic imbalance. Using an ex vivo wound fluid model, we show the ability of a proprietary new wound treatment to bind and inactivate proteases. We have shown that the addition of this test material to human chronic wound fluid obtained from diabetic foot ulcer patients resulted in a significant reduction in the activities of neutrophil-derived elastase, plasmin, and matrix metalloproteinase when compared to wet gauze. This study provides mechanistic evidence to support the hypothesis that this novel treatment modality for chronic wounds physically modifies the wound microenvironment, and thereby promotes granulation tissue formation and stimulates wound repair.
蛋白酶在伤口修复的许多生理过程中起着关键作用。然而，如果它们的活性不受控制，蛋白酶会介导严重的组织损伤，因此它们与慢性伤口的病理生理学有关。先前的研究表明，慢性伤口渗出液中蛋白酶水平升高，具有有害作用，会降解新生肉芽组织以及内源性生物活性蛋白，如生长因子和细胞因子。因此，我们提出，一种针对慢性伤口的有效治疗方法是改变这种不利环境并纠正这种蛋白水解失衡。使用体外伤口渗出液模型，我们展示了一种专有的新型伤口治疗方法结合并使蛋白酶失活的能力。我们已经表明，将这种测试材料添加到从糖尿病足溃疡患者获得的人慢性伤口渗出液中，与湿纱布相比，中性粒细胞弹性蛋白酶、纤溶酶和基质金属蛋白酶的活性显著降低。这项研究提供了机制证据，以支持这一假设，即这种针对慢性伤口的新型治疗方式通过物理方式改变伤口微环境，从而促进肉芽组织形成并刺激伤口修复。
