The effect of matrix metalloproteinase inhibition on tendon-to-bone healing in a rotator cuff repair model

J Shoulder Elbow Surg. 2010 Apr;19(3):384-91. doi: 10.1016/j.jse.2009.07.010. Epub 2009 Oct 2.


Hypothesis: Recent studies have demonstrated a potentially critical role of matrix metalloproteinases (MMPs) and tissue inhibitors of matrix metalloproteinases (TIMPs) in the pathophysiology of rotator cuff tears. We hypothesize that local delivery of a MMP inhibitor after surgical repair of the rotator cuff will improve healing at the tendon-to-bone surface interface.

Materials and methods: Sixty-two male Sprague-Dawley rats underwent acute supraspinatus detachment and repair. In the control group (n=31), the supraspinatus was repaired to its anatomic footprint. In the experimental group (n=31), recombinant alpha-2-macroglobulin (A2M) protein, a universal MMP inhibitor, was applied at the tendon-bone interface with an identical surgical repair. Animals were sacrificed at 2 and 4 weeks for histomorphometry, immunohistochemistry, and biomechanical testing. Statistical comparisons were performed using unpaired t tests. Significance was set at P < .05.

Results: Significantly greater fibrocartilage was seen at the healing enthesis in the A2M-treated specimens compared with controls at 2 weeks (P < .05). Significantly greater collagen organization was observed in the A2M-treated animals compared with controls at 4 weeks (P < .01). A significant reduction in collagen degradation was observed at both 2 and 4 weeks in the experimental group (P < .05). Biomechanical testing revealed no significant differences in stiffness or ultimate load-to-failure.

Conclusion: Local delivery of an MMP inhibitor is associated with distinct histologic differences at the tendon-to-bone interface after rotator cuff repair. Modulation of MMP activity after rotator cuff repair may offer a novel biologic pathway to augment tendon-to-bone healing after rotator cuff repair.

MeSH terms

  • Animals
  • Biomechanical Phenomena
  • Bone and Bones / drug effects*
  • Bone and Bones / physiopathology
  • Collagen / biosynthesis
  • Disease Models, Animal
  • Enzyme Inhibitors / pharmacology
  • Fibrocartilage / physiology
  • Male
  • Matrix Metalloproteinase Inhibitors*
  • Rats
  • Rats, Sprague-Dawley
  • Rotator Cuff / physiopathology*
  • Rotator Cuff / surgery
  • Tendons / drug effects*
  • Tendons / physiopathology
  • Wound Healing / drug effects*
  • alpha-Macroglobulins / pharmacology


  • Enzyme Inhibitors
  • Matrix Metalloproteinase Inhibitors
  • alpha-Macroglobulins
  • Collagen