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

• Published in: Journal of shoulder and elbow surgery 2010-04, Vol.19 (3), p.384-391
• Main Authors: Bedi, Asheesh, MD, Kovacevic, David, MD, Hettrich, Carolyn, MD, Gulotta, Lawrence V., MD, Ehteshami, John R., MD, Warren, Russell F., MD, Rodeo, Scott A., MD
• Format: Article
• Language: English
• Subjects: alpha-Macroglobulins - pharmacology; Animals; Biological and medical sciences; Biomechanical Phenomena; Bone and Bones - drug effects; Bone and Bones - physiopathology; Collagen - biosynthesis; Disease Models, Animal; Diseases of the osteoarticular system; Enzyme Inhibitors - pharmacology; Fibrocartilage - physiology; inhibitor; Male; Matrix metalloproteinase; Matrix Metalloproteinase Inhibitors; Medical sciences; Orthopedics; Rats; Rats, Sprague-Dawley; Rotator Cuff - physiopathology; Rotator Cuff - surgery; rotator cuff repair; tendon-bone healing; Tendons - drug effects; Tendons - physiopathology; Wound Healing - drug effects
• ISSN: 1058-2746; 1532-6500
• DOI: 10.1016/j.jse.2009.07.010

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 α-2-macroglobulin (A2 M) 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 A2 M-treated specimens compared with controls at 2 weeks ( P < .05). Significantly greater collagen organization was observed in the A2 M-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.