The effects of N-acetylcysteine and adipose-derived stem cells on tendon healing in chronic rotator cuff tears: a rabbit model study.

Abstract

BACKGROUND: Rotator cuff tears are associated with significant morbidity, and retear rates after surgical repair remain high, largely due to chronic degenerative changes such as muscle atrophy and fatty infiltration. This study aims to evaluate the effects of locally injected adipose tissue-derived stem cells and orally administered N-acetylcysteine, individually and in combination, on tendon healing in a rabbit model of chronic rotator cuff rupture. METHODS: Thirty-two male New Zealand white rabbits were used as models of chronic rotator cuff tear, surgically established by detaching the supraspinatus tendon and delaying repair to create a chronic defect. The rabbits were divided into four groups: Group A (control, saline-treated), Group B (N-acetylcysteine-treated), Group C (adipose tissue-derived stem cells-treated), and Group D (combined adipose tissue-derived stem cells and N-acetylcysteine-treated). Chronic rotator cuff tear repairs were conducted after six weeks. Histological, immunohistochemical, and biomechanical assessments were performed 12 weeks post-repair. Key outcomes included collagen organization, fatty infiltration, type I collagen expression, and tensile strength. RESULTS: Histopathological analysis revealed significantly improved collagen fiber alignment, reduced fatty infiltration, and decreased inflammation in Groups C and D compared to Groups A and B (p&#x2009;<&#x2009;0.001). Immunohistochemical analysis revealed higher Type I collagen reactivity in Groups C and D, with Group D exhibiting the highest reactivity (p&#x2009;<&#x2009;0.001). Biomechanical testing confirmed significantly increased load to failure in Groups C and D, with Group D achieving the highest values (p&#x2009;<&#x2009;0.001). CONCLUSIONS: Adipose tissue-derived stem cells and N-acetylcysteine independently promote tendon healing, with adipose tissue-derived stem cells showing superior effects on collagen organization and fatty infiltration reduction. Combined treatment with adipose tissue-derived stem cells and N-acetylcysteine demonstrated synergistic effects, resulting in optimal tendon regeneration and strength. These findings support the potential of adipose tissue-derived stem cells and N-acetylcysteine as complementary therapies for chronic rotator cuff injuries. Further research is warranted to explore their mechanisms of action and clinical applications.