Bench-to-bedside: Bridge-enhanced anterior cruciate ligament repair

Abstract

Anterior cruciate ligament (ACL) injuries are one of the most well-known orthopaedic injuries and are treated with one of the most common orthopaedic procedures performed in the United States. This surgical procedure, ACL reconstruction, is successful at restoring the gross stability of the knee. However, the outcomes of ACL reconstruction can be limited by short and long-term complications, including muscle weakness, graft rupture, and premature osteoarthritis. Thus, new methods of treating this injury are being explored. This review details the pathway of how a tissue engineering strategy can be used to improve the healing of the ACL in preclinical studies and then translated to patients in an FDA-approved clinical study. This review paper will outline the clinical importance of ACL injuries, history of primary repair, the pathology behind failure of the ACL to heal, pre-clinical studies, the FDA approval process for a high risk medical device, and the preliminary results from a first-in-human study. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:2606-2612, 2017.

Keywords: biomaterials, repair and tissue engineering; cell biology; knee ligament; surgical repair.

Figure 1

The primary defect for healing of intra-articular injuries. Wounds for tissues outside of the joint (like the MCL) fill with a bioactive fibrin clot after injury. In contrast, wounds inside the joint (intra-articular, like the ACL) fail to form this provisional scaffold and, therefore, are missing a key component of successful wound healing. The wound remains open, and healing cannot occur (Used with permission from Murray and Spindler 2005 [68])

Figure 2

The distal femur cartilage 1-year after A) an untreated ACL rupture, B) after conventional ACL reconstruction, C) after bridge-enhanced ACL repair, and D) after bridge-enhanced ACL reconstruction. Note the damage to the medial femoral condyle in the untreated, ACL reconstructed knees, and bridge-enhanced ACL reconstructed knees (black arrows), and the lack of damage in the medial femoral condyle in the bridge-enhanced ACL repair and bridge-enhanced ACL reconstructed knees (white arrow) [61]. (Used with permission from Murray and Fleming 2013)

Figure 3

Stepwise demonstration of the “Bridge-Enhanced ACL repair” technique using the collagen-based scaffold. In this technique, the torn ACL tissue is preserved (A). A whip stitch of #2 absorbable suture (purple suture) is placed into the tibial stump of the ACL. Small tunnels (4 mm) are drilled in the femur and tibia and an extracortical button with two #2 nonabsorbable sutures (green sutures) and the #2 absorbable ACL sutures attached to it is passed through the femoral tunnel and engaged on the proximal femoral cortex. The nonabsorbable sutures (green) are threaded through the scaffold, tibial tunnel and secured in place with a second extracortical button. The collagen-based scaffold is then saturated with 5 mL of the patient’s blood (B), and the tibial stump pulled up into the saturated scaffold (C). The ends of the torn ACL then grow into the collagen-based scaffold and the ligament reunites (D). (Used with permission from Murray et al. 2016[67]).