Fetz Allison E, Bowlin Gary L
Department of Biomedical Engineering, University of Memphis, Memphis, Tennessee, USA.
Tissue Eng Part B Rev. 2022 Apr;28(2):437-450. doi: 10.1089/ten.TEB.2021.0013. Epub 2021 May 11.
Tissue injury initiates a tissue repair program, characterized by acute inflammation and recruitment of immune cells, dominated by neutrophils. Neutrophils prevent infection in the injured tissue through multiple effector functions, including the production of reactive oxygen species, the release of granules, the phagocytosis of invaders, and the extrusion of neutrophil extracellular traps (NETs). However, these canonical protective mechanisms can also have detrimental effects both in the context of infection and in response to sterile injuries. Of particular interest to biomaterials and tissue engineering is the release of NETs, which are extracellular structures composed of decondensed chromatin and various toxic nuclear and granular components. These structures and their dysregulated release can cause collateral tissue damage, uncontrolled inflammation, and fibrosis and prevent the neutrophil from exerting its prohealing functions. This review discusses our knowledge of NETs, including their composition and morphology, signaling pathways, inhibitors, and contribution to inflammatory pathologies, as well as their role in the resolution of inflammation. In addition, we summarize what is known about the release of NETs as a preconditioning event in the response to biomaterials and highlight future considerations to target the neutrophil response and enhance biomaterial-guided tissue repair and regeneration. Impact statement Neutrophil extracellular trap (NET) release is an active process programmed into the neutrophil's molecular machinery to prevent infection. However, the release of NETs on biomaterials appears to be a significant preconditioning event that influences the potential for tissue healing with largely detrimental consequences. Given their contribution to inflammatory pathologies, this review highlights the role of NETs in the response to biomaterials. Together, the studies discussed in this review suggest that biomaterials should be designed to regulate NET release to avoid maladaptive immune responses and improve the therapeutic potential of tissue-engineered biomaterials and their applications in the clinical setting.
组织损伤启动组织修复程序，其特征为急性炎症和免疫细胞募集，其中以中性粒细胞为主导。中性粒细胞通过多种效应功能预防受损组织感染，这些功能包括活性氧的产生、颗粒释放、病原体吞噬以及中性粒细胞胞外陷阱（NETs）的挤出。然而，这些典型的保护机制在感染情况下以及对无菌性损伤的反应中也可能产生有害影响。对于生物材料和组织工程而言，特别值得关注的是NETs的释放，NETs是由解聚的染色质以及各种有毒的核成分和颗粒成分组成的细胞外结构。这些结构及其失调的释放可导致附带组织损伤、不受控制的炎症和纤维化，并阻碍中性粒细胞发挥其促进愈合的功能。本综述讨论了我们对NETs的认识，包括其组成和形态、信号通路、抑制剂以及对炎症性疾病的影响，以及它们在炎症消退中的作用。此外，我们总结了关于NETs释放作为对生物材料反应中的预处理事件的已知信息，并强调了针对中性粒细胞反应以及增强生物材料引导的组织修复和再生的未来考虑因素。影响声明中性粒细胞胞外陷阱（NET）的释放是中性粒细胞分子机制中设定的一个主动过程，用于预防感染。然而，生物材料上NETs的释放似乎是一个重要的预处理事件，它影响组织愈合的潜力，且大多会产生有害后果。鉴于它们对炎症性疾病的影响，本综述强调了NETs在对生物材料反应中的作用。本综述中讨论的研究共同表明，生物材料的设计应旨在调节NET的释放，以避免适应不良的免疫反应，并提高组织工程生物材料的治疗潜力及其在临床环境中的应用。
