Effects of Extracorporeal Shock Wave Therapy on Tendon Integrity, Biomechanical Strength, Matrix Remodeling, Inflammation, Angiogenesis, and Tenogenic Differentiation in Rotator Cuff Injury

Extracorporeal shock wave therapy (ESWT) improves tendon-bone healing after rotator cuff injury (RCI), but its underlying cellular mechanisms remain unknown. This study aimed to explore the therapeutic effects of ESWT on RCI, with a particular focus on endothelial cells and tenocytes. The RCI model was established in rabbits by rotator cuff tear surgery, followed by ESWT intervention. Histological evaluation, blood perfusion analysis, biomechanical testing, and assessment of inflammation and extracellular matrix (ECM) degradation were performed in RCI-treated rabbits at week (W) 2, W4, and W8. For the in vitro experiments, human umbilical vein endothelial cells (HUVECs) and human tenocytes were treated with ESWT. ESWT reduced Bonar scores, increased the fibrocartilage area and collagen-positive area, and enhanced blood perfusion and biomechanical strength at most time points in RCI rabbits (all p < 0.05). Moreover, ESWT reduced inflammation and ECM degradation, as reflected by reduced tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and IL-6 and decreased matrix metalloproteinase (MMP)-1 and MMP-9 at most time points in RCI rabbits (all p < 0.05). In HUVECs, ESWT increased proliferation, invasion, branch points, MMP-2, MMP-9, vascular endothelial growth factor A (VEGFA), and fibroblast growth factor 2 (FGF2) (all p < 0.05). In tenocytes, ESWT increased proliferation, collagen I, thrombospondin-4 (TSP4), VEGFA, FGF2, tenomodulin (TNMD), and scleraxis (SCX) (all p < 0.05). ESWT improves tendon integrity, blood perfusion, and biomechanical strength while reducing inflammation and ECM degradation after RCI, possibly via enhanced angiogenic activity in endothelial cells and maintenance of the tenogenic phenotype in tenocytes.