Chow Simon Kwoon-Ho, Wong Carissa Hing-Wai, Cui Can, Li Michelle Meng-Chen, Wong Ronald Man Yeung, Cheung Wing-Hoi
Department of Orthopaedics and Traumatology, The Chinese University of Hong Kong, Hong Kong SAR, China.
J Orthop Translat. 2022 Aug 5;36:83-90. doi: 10.1016/j.jot.2022.05.004. eCollection 2022 Sep.
All fracture repairs start with the innate immune system with the inflammatory response known as the inflammatory stage guided and driven by the secretion of chemokine by the ruptured tissue, followed by the sequential recruitment of neutrophils, monocytes and macrophages. These innate immune cells would infiltrate the fracture site and secrete inflammatory cytokines to stimulate recruitment of more immune cells to arrive at the fracture site coordinating subsequent stages of the repair process. In which, subsidence of pro-inflammatory M1 macrophage and transformation to anti-inflammatory M2 macrophages promotes osteogenesis that marks the start of the anabolic endochondral stage.
Literature search was performed on Pubmed, Embase, and Web of Science databases (last accessed 15th April 2021) using "macrophage AND fracture". Review was performed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guideline.
Eleven pre-clinical animal studies out of 429 articles were included in this systematic review according to our inclusion and exclusion criteria. All of which investigated interventions targeting to modulate the acute inflammatory response and macrophage polarization as evident by various markers in association with fracture healing outcomes.
This systematic review summarizes attempts to modulate the innate immune response with focuses on promoting macrophage polarization from M1 to M2 phenotype targeting the enhancement of fracture injury repair. Methods used to achieve the goal may include applications of damage-associated molecular pattern (DAMP), pathogen-associated molecular pattern (PAMP) or mechanical stimulation that hold high translational potentials for clinical application in the near future.
所有骨折修复均始于固有免疫系统，其炎症反应即炎症阶段由破裂组织分泌的趋化因子引导和驱动，随后依次募集嗜中性粒细胞、单核细胞和巨噬细胞。这些固有免疫细胞会浸润骨折部位并分泌炎性细胞因子，以刺激更多免疫细胞募集至骨折部位，从而协调修复过程的后续阶段。其中，促炎M1巨噬细胞的消退及向抗炎M2巨噬细胞的转变促进骨生成，标志着合成代谢性软骨内阶段的开始。
在PubMed、Embase和Web of Science数据库（最后访问时间为2021年4月15日）上使用“巨噬细胞与骨折”进行文献检索。根据系统评价和Meta分析的首选报告项目（PRISMA）指南进行综述。
根据纳入和排除标准，本系统评价纳入了429篇文章中的11项临床前动物研究。所有研究均调查了旨在调节急性炎症反应和巨噬细胞极化的干预措施，各种标志物与骨折愈合结果相关，这一点很明显。
本系统评价总结了调节固有免疫反应的尝试，重点是促进巨噬细胞从M1表型向M2表型极化，以增强骨折损伤修复。用于实现这一目标的方法可能包括应用损伤相关分子模式（DAMP）、病原体相关分子模式（PAMP）或机械刺激，这些方法在不久的将来具有很高的临床应用转化潜力。
