Failed healing of rotator cuff repair correlates with altered collagenase and gelatinase in supraspinatus and subscapularis tendons

Am J Sports Med. 2012 Sep;40(9):1993-2001. doi: 10.1177/0363546512456519. Epub 2012 Aug 15.


Background: Despite improvements in arthroscopic rotator cuff repair technique and technology, a significant rate of failed tendon healing persists. Improving the biology of rotator cuff repairs may be an important focus to decrease this failure rate. The objective of this study was to determine the mRNA biomarkers and histological characteristics of repaired rotator cuffs that healed or developed persistent defects as determined by postoperative ultrasound.

Hypothesis: Increased synovial inflammation and tendon degeneration at the time of surgery are correlated with the failed healing of rotator cuff tendons.

Study design: Case-control study; Level of evidence, 3.

Methods: Biopsy specimens from the subscapularis tendon, supraspinatus tendon, glenohumeral synovium, and subacromial bursa of 35 patients undergoing arthroscopic rotator cuff repair were taken at the time of surgery. Expression of proinflammatory cytokines, tissue remodeling genes, and angiogenesis factors was evaluated by quantitative real-time polymerase chain reaction. Histological characteristics of the affected tissue were also assessed. Postoperative (>6 months) ultrasound was used to evaluate the healing of the rotator cuff. General linear modeling with selected mRNA biomarkers was used to predict rotator cuff healing.

Results: Thirty patients completed all analyses, of which 7 patients (23%) had failed healing of the rotator cuff. No differences in demographic data were found between the defect and healed groups. American Shoulder and Elbow Surgeons shoulder scores collected at baseline and follow-up showed improvement in both groups, but there was no significant difference between groups. Increased expression of matrix metalloproteinase 1 (MMP-1) and MMP-9 was found in the supraspinatus tendon in the defect group versus the healed group (P = .006 and .02, respectively). Similar upregulation of MMP-9 was also found in the subscapularis tendon of the defect group (P = .001), which was consistent with the loss of collagen organization as determined by histological examination. From a general linear model, the upregulation of MMP-1 and MMP-9 was highly correlated with failed healing of the rotator cuff (R(2) = .656).

Conclusion: The upregulation of tissue remodeling genes in the torn rotator cuff at the time of surgery provides a snapshot of the biological environment surrounding the torn rotator cuff that is closely related to the healing of repaired rotator cuffs.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Arthroscopy
  • Biomarkers
  • Case-Control Studies
  • Collagenases / genetics*
  • Female
  • Gelatinases / genetics*
  • Humans
  • Male
  • Middle Aged
  • Rotator Cuff / diagnostic imaging*
  • Rotator Cuff / pathology*
  • Rotator Cuff / surgery
  • Rotator Cuff Injuries
  • Tendons / pathology
  • Tendons / physiopathology*
  • Treatment Failure
  • Ultrasonography
  • Wound Healing / genetics*
  • Wound Healing / physiology


  • Biomarkers
  • Collagenases
  • Gelatinases