Eccentric Mechanical Stimulation Promotes Rotator Cuff Healing by Regulating Macrophage Polarization in a Murine Model.

Abstract

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, due to their polarization. This study aims to investigate the role of macrophages in rotator cuff injury repair promoted by EMS. A total of 96 male C57BL/6 mice were used to establish a rotator cuff injury repair model and were randomly divided into four groups: Control, EMS, control + clodronate liposomes (Con-CL), and EMS-CL groups. Specimens were collected at two and four weeks postoperatively for histological, radiological, immunohistochemical, and biomechanical analyses. At two weeks postoperatively, the EMS group exhibited a thicker fibrocartilage layer and increased expression of M2 macrophages compared to other groups. At four weeks, histological 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-CT results showed superior bone volume fraction (BV/TV), trabecular number (Tb.N), and trabecular thickness (Tb.Th) in the EMS group. Biomechanical testing indicated higher failure load (FL) and ultimate strength (US) in the EMS group. The positive effects of mechanical stimulation were significantly diminished after macrophage depletion using CL. Macrophages may play a crucial role in the repair of rotator cuff injuries promoted by eccentric mechanical stimulation. The therapeutic benefits are partly attributed to the regulation of macrophage function, with eccentric mechanical stimulation reducing M1 macrophage expression and enhancing M2 macrophage polarization. This promotes rotator cuff tendon-bone injuries healing and suggests that targeting macrophage polarization may have positive effects on tendon-bone interface injuries recovery healing in rotator cuff repair. Basic Science Study; In Vivo Animal Model.