Some wounds do not follow the typical healing trajectory and show very little, if any, progress. They dreadfully threaten the patients' quality of life and may even lead to limb amputation and death. Several interrelated systemic and local factors may cause a delay in wound healing. The microenvironment of these wounds can be different from wounds that heal spontaneously or with standard treatment. As discussed in the present work, proteases’ levels or activity can be elevated in some cases of chronic ulcers; infection can aggravate the situation. A detailed overview of the proteases’ effect on wound healing is presented in this work. Assuming untimely or irregularly excessive proteolytic activity plays a pathological role, some researchers targeted attenuation of protease level as a strategy to promote healing. This can be done via different approaches, including physical removal, inhibiting their activity, and controlling their expression directly through gene silencing or indirectly, for instance, by resolving infection. Apart from targeting protease modulation as a therapeutic strategy, many studies have examined the protease state to gain insights into the underlying mechanisms by which a remedy, dressing, or specific therapy has affected the healing process. This study aims to provide an overview of the studies in these two categories. Of course, various proteases are involved in the healing process, but in each study, usually, only one or some of them are investigated; matrix metalloproteinase-2 (MMP-2), MMP-9, and human neutrophil elastase (HNE) are among them. Furthermore, in some cases, cumulative proteolytic activity is evaluated in terms of gelatinolytic, collagenolytic, or caseinolytic activity, which is also absolutely beneficial. Some research groups have considered the potential of proteases as a diagnostic or prognostic biomarker and have tried to develop some sensors or indicators; this topic is also covered in the present work.

中文翻译：

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控制和监测慢性伤口中蛋白酶水平的方法

有些伤口不遵循典型的愈合轨迹，即使有进展，也很少。它们严重威胁患者的生活质量，甚至可能导致截肢和死亡。一些相互关联的全身和局部因素可能会导致伤口愈合延迟。这些伤口的微环境可能与自然愈合或标准治疗的伤口不同。正如本研究中所讨论的，在某些慢性溃疡病例中，蛋白酶的水平或活性可能会升高。感染会使情况恶化。这项工作详细概述了蛋白酶对伤口愈合的影响。假设不合时宜或不规则的过度蛋白水解活性发挥病理作用，一些研究人员将降低蛋白酶水平作为促进愈合的策略。这可以通过不同的方法来完成，包括物理去除、抑制其活性以及通过基因沉默直接控制其表达或通过解决感染等间接控制其表达。除了将蛋白酶调节作为治疗策略外，许多研究还检查了蛋白酶状态，以深入了解药物、敷料或特定疗法影响愈合过程的潜在机制。本研究旨在概述这两​​类研究。当然，愈合过程涉及多种蛋白酶，但在每项研究中，通常只研究其中的一种或部分；其中包括基质金属蛋白酶-2 (MMP-2)、MMP-9 和人中性粒细胞弹性蛋白酶 (HNE)。此外，在某些情况下，根据明胶分解、胶原分解或酪蛋白分解活性来评估累积的蛋白水解活性，这也是绝对有益的。一些研究小组考虑了蛋白酶作为诊断或预后生物标志物的潜力，并尝试开发一些传感器或指示器；目前的工作也涵盖了这个主题。