Current status and potential of primary ACL repair

Abstract

Anterior cruciate ligament (ACL) rupture occurs in hundreds of thousands of active adolescents and young adults each year. Despite current treatment, posttraumatic osteoarthritis following these injuries is common in these young patients. Thus, there is widespread clinical and scientific interest in improving patient outcomes and preventing osteoarthritis. The current emphasis on the removal of the torn ACL and subsequent replacement with a tendon graft (ACL reconstruction) stems from adherence to a long-held and widely accepted doctrine that the ACL has only a limited healing response and, therefore, cannot heal or regenerate with suture repair. Recent work has shown that, despite an active biologic response in the ACL after injury, the two ends of the torn ligament never reconnect. Additional studies have detailed findings after placement of a substitute provisional scaffold in the wound site of the ACL injury to bridge the gap and initiate healing of the ruptured ligament after primary repair. This technique, called enhanced primary repair, has significant potential advantages over current ACL reconstruction techniques, including the preservation of the complex attachment sites and innervation of these structures, thus retaining much of the biomechanical and proprioceptive function of these tissues. This manuscript summarizes the recent in vitro and in vivo studies in the area of enhancing ACL healing using biologic supplementation. Subsequent work in this area may lead to the development of a novel approach to treat this important injury.

FIGURE 1A and B

Schematic of the enhanced suture repair technique. In 1A, the location of the ACL between femur and tibia is illustrated. The enlarged view on the right (1B) shows a transected ACL treated with suture repair where the sutures are attached to an anchor in the bone at the femoral insertion site and then are passed through the longer distal ACL segment and tied to reapproximate the proximal and distal ACL segments. The growth factor hydrogel is introduced into the wound site to stimulate biologic repair. (Reproduced with permission from Murray MM, Spindler KP, Abreu E, et al. Collagen-platelet rich plasma hydrogel enhances primary repair of the porcine anterior cruciate ligament. J Orthop Res. 2007;25:81–91).

Figure 2

Premature osteoarthritis after anterior cruciate ligament (ACL) injury. Radiographs of a 40 year old man who had sustained an ACL rupture 20 years earlier. Note the joint space narrowing and osteophyte formation consistent with premature osteoarthritis (arrow) on the medial aspect of the left knee (knee with ACL tear) and the preservation of medial joint space in the knee with the intact ACL on the right (arrow).

Figure 3

Histologic response of the human ACL to rupture. A. Histologic appearance of the normal ACL showing fibroblasts (blue nuclei; 40X). B. Histologic appearance of ACL tissue 3 months after rupture showing increased cell density in the ligament ends (40X). C. Area of increased vessel density in ruptured ACL fragments at 3 months after injury (20X). D) Synovial layer which has reformed over the ligament ends at 8 weeks after rupture (BV = blood vessel, 40X). Sections are immunohistochemistry for alpha-smooth muscle actin (SMA) where red demonstrates a positive stain for SMA, with a blue counter-stain for cell nuclei18.

Figure 4

Representative micrographs of slit wounds made with a modified Beaver blade in the center of the MCL and ACL seven days earlier in a canine knee. Note that the MCL wound is filled with a provisional scaffolding material containing high amounts of multiple growth factors important in tissue healing (here, immunohistochemistry for FGF-2 where red is a positive stain). In the ACL wound, however, the defect remains unfilled, even after seven days. (Adapted with permission from Steiner, ME, Murray, M.M. and Rodeo, S.A. Strategies to Improve Anterior Cruciate Ligament Healing and Graft Placement, American Journal of Sports Medicine, 2008, 36(10), pages 176–8923.)

Figure 5

Representative micrographs of the wound site in the extra-articular patellar ligament (EA row) and the intra-articular ACL (IA row) after three weeks in vivo. Note the filling of the wound site in the EA ligament with an active repair process occurring within the provisional scaffold (top row). In contrast, the ACL wounds remain unfilled (bottom row) 25. (Reproduced with permission from Murray, MM., Spindler, K.P., Ballard, P., Welch, T., Nanney, LB. Enhanced Histologic Repair in a Central Defect in the ACL with a Collagen-PRP Scaffold. J Orthop Res, 2007, 25(8):1007–1017.)

Figure 6

Proposed pathway for accelerated fibrinolysis after joint injury. The increased secretion of urokinase plasminogen activator (u-PA) results in high levels of plasmin in the inflammatory synovial fluid. This is a likely mechanism for the accelerated fibrinolysis noted in the joint after injury. (t-PA: tissue plasminogen activator. PAI-1 and 2: Plasminogen activator inhibitor 1 and 2. uPAR: urokinase-type plasminogen activator receptor.

Figure 7

Novel hypothesis of the failure of ACL healing. For the medial collateral ligament (MCL) which is outside the joint, injury is followed by formation of a provisional scaffold in the form of a fibrin clot. The scaffold is gradually remodeled as the tissue heals (top row). No fibrin clot is found at the injury site of the anterior cruciate ligament (ACL), which is inside the knee joint. Without a provisional scaffold, the wound site remains empty and healing cannot proceed.

Figure 8

Load at yield and maximum load for the three groups: suture repair alone (Suture), suture repair plus collagen-platelet composite (Suture/PRP), and intact ACLs (Intact ACL). Differences were observed between intact ACLs and each of the other two groups (denoted by #). Load at yield and maximum load were both significantly higher for suture repair plus collagen-platelet composite compared to suture repair alone as denoted by asterisks. Error bars represent standard deviations. Arrow designates yield strength of ACL reconstruction at a similar time point44. (Adapted with permission from Steiner, ME, Murray, M.M. and Rodeo, S.A. Strategies to Improve Anterior Cruciate Ligament Healing and Graft Placement, American Journal of Sports Medicine, 2008, 36(10), pages 176–8923.).