机械力与巨噬细胞在骨伤疾病治疗中的研究进展与临床应用

Research Progress and Clinical Application of Mechanical Force and Macrophages in the Treatment of Bone Injury Diseases

摘要: 巨噬细胞作为先天免疫系统的核心成员，在组织稳态维持、损伤修复和炎症调控中扮演着不可替代的角色。近年来，随着生物力学与免疫学的交叉融合，机械力调控巨噬细胞功能已成为骨科疾病治疗的新兴研究方向。本文系统综述了机械力(包括流体剪切力、拉伸应力和压缩力等)通过调控巨噬细胞极化、迁移和吞噬功能影响骨伤修复的分子机制，重点探讨了其在骨关节炎、骨折愈合和骨肿瘤治疗中的转化应用。研究表明，适度的机械刺激可促进巨噬细胞向抗炎M2型极化，增强其组织修复能力；而异常的力学负荷则可能导致促炎M1型巨噬细胞过度活化，加剧组织损伤。基于“力学–免疫–再生”轴的新型治疗策略，如力学免疫调节材料(mechano-immunomodulatory materials)和靶向巨噬细胞机械敏感通道的药物治疗，为骨科疾病的精准干预提供了全新思路。深入理解机械力与巨噬细胞的相互作用机制，将推动骨科治疗从单纯的力学固定或药物干预向多模态协同治疗的范式转变。

Abstract: As a key member of the innate immune system, macrophages play an irreplaceable role in maintaining tissue homeostasis, facilitating injury repair, and regulating inflammation. In recent years, with the interdisciplinary integration of biomechanics and immunology, the regulation of macrophage functions by mechanical forces has emerged as a burgeoning research direction in the treatment of orthopedic diseases. This article systematically reviews the molecular mechanisms through which mechanical forces (including fluid shear stress, tensile stress, and compressive force, among others) influence bone injury repair by regulating macrophage polarization, migration, and phagocytic functions, with a focus on exploring their translational applications in the treatment of osteoarthritis, fracture healing, and bone tumors. Studies have demonstrated that moderate mechanical stimulation can promote the polarization of macrophages toward the anti-inflammatory M2 phenotype, enhancing their tissue repair capabilities; conversely, abnormal mechanical loading may lead to excessive activation of pro-inflammatory M1 macrophages, exacerbating tissue damage. Novel therapeutic strategies based on the “mechanics-immunity-regeneration” axis, such as mechano-immunomodulatory materials and drug therapies targeting macrophage mechanosensitive channels, offer entirely new perspectives for the precise intervention of orthopedic diseases. A profound understanding of the interaction mechanisms between mechanical forces and macrophages will drive a paradigm shift in orthopedic treatment from mere mechanical fixation or drug intervention to multimodal synergistic therapy.