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


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.


CONCLUSIONS
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.
Sports Medicine and Shoulder Surgery, Laboratory for Soft Tissue Research, Hospital for Special Surgery, New York, NY 10021, USA.
Asheesh
A
Bedi
David
D
Kovacevic
Carolyn
C
Hettrich
Lawrence V
LV
Gulotta
John R
JR
Ehteshami
Russell F
RF
Warren
Scott A
SA
Rodeo
D000818:Animals; D001696:Biomechanical Phenomena; D001842:Bone and Bones / Q000187:drug effects* / Q000503:physiopathology; D003094:Collagen / Q000096:biosynthesis; D004195:Disease Models, Animal; D004791:Enzyme Inhibitors / Q000494:pharmacology; D051445:Fibrocartilage / Q000502:physiology; D008297:Male; D061965:Matrix Metalloproteinase Inhibitors; D051381:Rats; D017207:Rats, Sprague-Dawley; D017006:Rotator Cuff / Q000503:physiopathology* / Q000601:surgery; D013710:Tendons / Q000187:drug effects* / Q000503:physiopathology; D014945:Wound Healing / Q000187:drug effects*; D000511:alpha-Macroglobulins / Q000494:pharmacology
D004791:Enzyme Inhibitors; D061965:Matrix Metalloproteinase Inhibitors; D000511:alpha-Macroglobulins; D003094:Collagen