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Synopsis: Unlike extra-articular ligaments that heal spontaneously, the torn ACL becomes covered with synovial myofibroblasts that cause retraction of the ends.
Source: Murray MM, et al. Histological changes in the human anterior cruciate ligament after rupture. J Bone Joint Surg Am 2000;82(10):1387-1397.
Unlike extra-articular ligaments, such as the MCL, the ACL does not heal spontaneously after rupture. Furthermore, efforts at primary repair have resulted in high failure rate because of the lack of ligamentous healing. The exact reasons why the ACL does not heal are speculative. Murray and colleagues have examined this issue by histologically inspecting both torn and intact ACL specimens retrieved at the time of surgery. Specimens were examined for cell and vascular density, collagen organization, and specifically for alpha-smooth muscle actin using immunohistochemical techniques with a mouse monoclonal antibody. Alpha-smooth muscle actin is present in contractile cells such as smooth muscle myofibroblasts.
Murray et al’s initial hypothesis was that following rupture, there would be an increase in the density at the tear site of myofibroblast-like cells known to be present within the substance of the ligament. However, they found that there was an actual decrease in the density of these cells. Therefore, their hypothesis changed as they noted other observations that seemed to explain the lack of healing of the ACL.
Once torn, the ACL goes through four phases described by Murray et al based on the histology. Phase I involves inflammation with an exudate of inflammatory cells surrounding the "mop-end" of the torn ligament. Little clot formation is present on the surface, and no bridging clot or connection between the torn ends is evident. The epiligamentous regeneration phase occurs between three and eight weeks after rupture with migration and proliferation of synovial cells on the surface of the ligament that stain positively for a-smooth muscle actin. These myofibroblast-type cells appear to contract, round off, and retract the torn ends of the ligament. Unlike extra-articular ligaments, the proliferation phase—phase III—didn’t begin until eight weeks following injury. Increased numbers of blood vessels as well as fibroblasts peaked at 20 weeks. The last phase involves remodelling and maturation of the ligament ends between one and two years after rupture.
This study helps us better understand cellular events associated with ACL rupture, the high rate of failure following primary repair, and opens doors for future interventions with biologics. Extra-articular ligament ruptures result in a bridging clot with rapid invasion by fibroblasts and gradual replacement by collagen fibers. This process occurs in the first few weeks following injury. Intra-articular ACL rupture does not follow with clot formation, as the presence of fibrinolytic enzymes in the synovial fluid keeps the hemarthrosis liquid. Thus, the normal healing response is blocked at the very beginning. Furthermore, the synovium migrates over the torn end of the ligaments, and the myofibroblast cells con-tract and smooth off the ends to prevent any hope of end-to-end contact.
Finally, the proliferative phase for fibroblast and new vessel ingrowth does not occur until 8-20 weeks after injury, much later than the first few weeks seen for extra-articular ligament tears. This is far too long for immobilization to allow any primary repair to occur. Interestingly, this is in contrast to other intra-articular structures that also do not heal, such as the avascular portion of the meniscus or articular cartilage, which never show a proliferative phase following injury.
This paper effectively enhances our understanding of why the ACL does not heal after rupture or primary repair, and perhaps may open doors for future studies that biologically manipulate the environment to stimulate the process.