Eccentric mechanical stimulation promotes rotator cuff healing by regulating macrophage polarization in a murine model.

Abstract

BACKGROUND: Eccentric mechanical stimulation (EMS) has been proposed as a potential therapy for tendon-bone injuries. Macrophages, as key immune cells, may play a significant role in promoting tendon-bone injury healing through mechanical stimulation, because of their polarization. This study aims to investigate the role of macrophages in rotator cuff injury repair promoted by EMS. METHODS: A total of 96 male C57BL/6 mice were used to establish a rotator cuff injury repair model and were randomly divided into 4 groups: Control, EMS, control + clodronate liposomes, and EMS + clodronate liposomes. Specimens were collected at 2 and 4 weeks postoperatively for histologic, radiologic, immunohistochemical, and biomechanical analyses. RESULTS: At 2 weeks postoperatively, the EMS group exhibited a thicker fibrocartilage layer and increased expression of M2 macrophages compared with other groups. At 4 weeks, histologic analysis revealed higher fibrocartilage and proteoglycan content in the EMS group, with increased local expression of M2 macrophages and reduced expression of M1 macrophages. Micro-computed tomography results showed superior bone volume-total volume fraction, trabecular bone number, and trabecular bone thickness in the EMS group. Biomechanical testing indicated higher failure load and ultimate strength in the EMS group. The positive effects of mechanical stimulation were significantly diminished after macrophage depletion using clodronate liposomes. CONCLUSION: Macrophages may play a crucial role in the repair of rotator cuff injuries promoted by EMS. The therapeutic benefits are partly attributed to the regulation of macrophage function, with EMS reducing M1 macrophage expression and enhancing M2 macrophage polarization. This promotes the healing of rotator cuff tendon-bone injuries and suggests that targeting macrophage polarization may have positive effects on tendon-bone interface injury recovery.