Purpose

The failure in timely healing of wounds is a central feature in chronic wounds that leads to physiological, psychological and economic burdens. Macrophages have been demonstrated to have various functions in wounds including host defense, the promotion and resolution of inflammation, the removal of apoptotic cells and tissue restoration following injury. Accumulated evidence suggests that macrophage dysfunction is a component of the pathogenesis of non-healing wounds. While the overall signaling cascades have been well understood, their complex interplay and a detailed characterization of events that are disrupted in chronic wounds have still not emerged satisfactorily.

Methods

The existing literature was reviewed to summarize the regulation of macrophage polarization in wound closure and dysregulation in non-healing wounds. Further, the review also underscored the role of Nrf2 in promoting macrophage-mediated regulation in wound responses and in particular, macrophage involvement in iron homeostasis that is impaired in chronic wounds such as in diabetes.

Results

The mechanisms involved in the reprogramming of macrophage subtypes in chronic wounds are still emerging. Furthermore, treating non-healing wounds has increasingly been shifting focus from generic treatments to the development of targeted therapies. Increasing evidence suggests the need for modeling wound tissue in vitro which may very well serve a critical aspect to characterize the relevant factors that sustain chronic wounds in vivo such as the constant iron overload at the wound site from recurrent infection and bleeding.

Conclusion

The development of targeted therapies and also developing a reliable means to monitor assisted healing of chronic wounds are two major goals to be pursued. In addition, identifying molecular targets that can regulate macrophages to aid tissue restoration in chronic wounds would serve the crucial step in realizing both aforementioned goals.

中文翻译：

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巨噬细胞在正常和糖尿病伤口愈合反应中的介导。

目的

伤口不能及时愈合是慢性伤口的主要特征，这导致生理，心理和经济负担。已经证明巨噬细胞在伤口中具有多种功能，包括宿主防御，炎症的促进和消退，凋亡细胞的去除以及损伤后组织的恢复。越来越多的证据表明，巨噬细胞功能障碍是伤口不愈合的原因之一。尽管已经全面理解了整个信号传导级联，但是它们的复杂相互作用和在慢性伤口中被破坏的事件的详细表征仍未令人满意。

方法

对现有文献进行了综述，以总结伤口愈合中巨噬细胞极化的调节和非愈合伤口的失调。此外，该综述还强调了Nrf2在促进巨噬细胞介导的伤口反应调节中的作用，尤其是巨噬细胞参与铁稳态中的铁稳态，而铁稳态在诸如糖尿病的慢性伤口中受损。

结果

慢性伤口中巨噬细胞亚型重编程的机制仍在出现。此外，治疗无法愈合的伤口越来越多地将重点从一般治疗转移到靶向治疗的发展。越来越多的证据表明，需要在体外​​对伤口组织进行建模，这可能非常有用，可以用来表征在体内维持慢性伤口的相关因素，例如由于反复感染和出血而在伤口部位持续不断的铁超负荷。

结论

靶向治疗的发展以及监测慢性伤口辅助愈合的可靠手段的开发是两个主要目标。另外，鉴定可调节巨噬细胞以帮助慢性伤口组织恢复的分子靶标将对实现上述两个目标至关重要。