The Effect of Vitamin C and -Acetylcysteine on Tendon-to-Bone Healing in a Rodent Model of Rotator Cuff Repair.

BACKGROUND

Oxidative stress inhibits tendon-to-bone healing after rotator cuff repair. Regulation of oxidative stress has the potential to accelerate this healing, but its mechanism remains unclear.

PURPOSE

To investigate the effects of reducing oxidative stress by applying antioxidants, such as -acetylcysteine (NAC) and vitamin C (VC), on rotator cuff repair in a rat rotator cuff repair model.

STUDY DESIGN

Controlled laboratory study.

METHODS

A total of 48 Sprague Dawley rats underwent bilateral surgery to repair the infraspinatus tendon to its insertion site 1 week after detachment. Rats were assigned to either the NAC group, the VC group, or a control group. Histological evaluation was performed via hematoxylin-eosin or toluidine blue staining, and oxidative stress was assessed via dihydroethidium intensity and protein carbonyl concentration at 3 and 6 weeks. Superoxide dismutase 1 (SOD1), SOD2, SOD3, peroxiredoxin 5, collagen type I (COL1), COL3, matrix metalloproteinase 1 (MMP-1), MMP-3, and MMP-13 expression and SOD activity were determined at 3 and 6 weeks. Biomechanical tests were performed at 6 and 12 weeks.

RESULTS

Histological evaluation showed that the number of chondrocytes in the NAC group at 6 weeks and in the VC group at 3 and 6 weeks, the area of fibrocartilage at 6 weeks in the VC group, and collagen fibers at 6 weeks in the NAC and VC groups were significantly increased compared with those in the control group. Dihydroethidium intensity at 3 and 6 weeks and protein carbonyls at 6 weeks in the NAC and VC groups were significantly decreased. SOD1 expression and SOD activity at 3 weeks in the VC group and peroxiredoxin 5 expression at 6 weeks in the NAC group were significantly upregulated compared with that in the control group. COL3 expression was significantly upregulated at 6 weeks in the VC group, and MMP-13 expression was significantly decreased at 6 weeks in the NAC and VC groups. The biomechanical strength showed no significant difference.

CONCLUSION

Antioxidant treatment, via NAC or VC administration, reduced oxidative stress in the rotator cuff repair site and accelerated healing.

CLINICAL RELEVANCE

These findings provide essential indications to develop clinical strategies for improved healing after rotator cuff surgical repair in patients.