Background: The use of soft-tissue grafts for anterior cruciate
ligament reconstruction delays the healing process. This delay may be due to
biochemical and/or biomechanical insults. We hypothesized that the blocking
effect of a2-macroglobulin on synovial matrix
metalloproteinase activity may enhance the healing of tendon graft in a bone
tunnel.
Methods: The study was performed on twenty-eight healthy, skeletally
mature New Zealand White rabbits. Each rabbit underwent bilateral anterior
cruciate ligament reconstruction with use of the ipsilateral semitendinosus
tendon. Alpha-2-macroglobulin (a2-macroglobulin) was injected
into the knee joint in one limb, and the contralateral limb served as a
control. The rabbits were killed two weeks (fourteen rabbits) or five weeks
(fourteen rabbits) after the operative procedures. The presence of matrix
metalloproteinases in synovial fluid, and the blocking effect of
a2-macroglobulin on them, were determined with enzymatic
assays. Healing between the tendon and the bone tunnel was assessed
morphologically by determining the presence of fibrovascular tissue and
collagen fibers. Healing also was assessed quantitatively by measuring the
ultimate load to failure of the reconstructed complex.
Results: There was an increase in matrix metalloproteinases in the
control group; in contrast, there was a decrease in the study group (p <
0.05). In the control specimens, the fibrovascular tissue at the bone-tendon
interface had developed into dense connective tissue with poor
vascularization. In the treated specimens, the bone tunnel had more areas of
denser connective-tissue ingrowth. The interface tissue was more mature and
contained numerous perpendicular collagen bundles (Sharpey fibers). The
ultimate load to failure was significantly greater in the
a2-macroglobulin-treated specimens than in the untreated
controls at both two and five weeks.
Conclusions: The present study demonstrated that
a2-macroglobulin blockade of matrix metalloproteinases can
enhance bone-tendon healing. This effect of a2-macroglobulin
could occur through its effect solely on collagenase or on a subset of matrix
metalloproteinases that are present at the healing interface.