PT Classroom - The latest research of ACL reconstruction and repair with an emphasis on the bridge-enhanced ACL repair (BEAR)  ׀ by Billie Weber, SPT


The latest research of ACL reconstruction and repair with an emphasis on the bridge-enhanced ACL repair (BEAR)

The anterior cruciate ligament (ACL) is an important stabilizer of the knee joint (1,2,3,4). It is an intracapsular structure that runs from the medial wall of the lateral femoral condyle to the anterior intercondylar area of the tibial plateau (3). The main function of the ACL is to act as a rotary guide in the screw home mechanism and to limit anterior translation and internal rotation of the tibia on the femur (2,3).

Each year, more than 200,000 ACL injuries occur in the United States (Figure 2) (5). Oftentimes, these injuries arise during high velocity movements, like cutting, pivoting, or landing a jump (3). They can occur at any age, but they tend to occur more frequently in young, active adults (2,3). Furthermore, women are 35 times more likely than men to sustain an ACL injury (6), especially if participating in sports that involve cutting and pivoting (1). ACL injuries can be treated conservatively with physical therapy, but 65% of the time, ACL ruptures are treated surgically.5 Surgical reconstruction involves removing the torn portions of the ACL and replacing it with a patellar or hamstring tendon graft. The graft is most often an autograft, but it could also be an allograft (2). While ACL reconstruction improves the overall stability of the knee, it does not prevent the development of post-traumatic osteoarthritis (2,4,6). One study found that post-traumatic osteoarthritis occurred as high as 78% of the time 14 years after injury (7).

Therefore, researchers are searching for a different approach to prevent post-traumatic osteoarthritis in surgically reconstructed knees. The latest research focuses on a bio-enhanced repair that involves the use of scaffolds, cell seeding, and growth factors to augment ACL primary suture repairs and reconstructions (4,9).

Scaffolds are bio-engineered tissues that serve to initiate and promote healing of the ACL. In a suture repair, scaffolds help to form a bridge between the torn ends of the ACL to allow for ligament regrowth and repair (4,8,9). Scaffolds have also been used to enhance reconstructions by placing it around the graft. Typically, scaffolds are designed to contain what is normally found in the extracellular matrix of the ligament. Therefore bio-active scaffolds are often seeded with cells and injected with platelets to release a variety of growth factors that are necessary for repair (8).

Cell seeding is another type of bio-enhanced repair technology that is being investigated (4,9). This technology involves supplementing the repair with exogenous cells, like fibroblasts or bone marrow stomal cells (BMSC), to enable faster and better healing of the ACL (4,9). One in vitro study showed that 10 times more collagen was produced when fibroblasts were added to a collagen scaffold. Another study compared ACL reconstructions with a non-seeded silk scaffold and a BMSC-seeded silk scaffold in a sheep model. The results from this study showed that the BMSC-seeded silk scaffold reconstructions had better healing as measured by histological evidence (9). Similar studies have found comparable results as evidenced by histological analysis, biomechanical evidence, and higher load-to-failure rates (4).

Growth factors are also being investigated for use in bio-enhanced ACL repairs. In vitro studies of epidermal growth factor (EGF), fibroblast growth factor (FGF), insulin-like growth factor (IGF), platelet-derived growth factor (PDGF), and transforming growth factor (TGF) increase collagen synthesis and cell proliferation (4,8,10). Several studies have shown the benefits of growth factors in vitro. However, growth factors face challenges in vivo. Typically endogenous growth factors are released by host cells in the human body over time; whereas exogenous growth factors are supplemented in a one-time dose. In addition, exogenous growth factors have been found to be cleared from the joint within a few hours (4,10). Thus researchers have been trying to find a better way to incorporate growth factors into the repair process.

Plasma-rich protein (PRP) contains a multitude of growth factors and has been used to successfully treat bony and soft tissue conditions in animal studies and clinical trials (10,11). Researchers have also attempted to stimulate the healing of ACL and ACL grafts with PRP and have observed varying results (4, 11). A systematic review concluded that the use of PRP in ACL reconstructions is slightly beneficial on graft maturation but has little to no effects on the healing of the graft-bone interface. The study went on to state that more research was necessary to determine the efficacy of PRP in the use of ACL healing. The mixed results seen in a variety of PRP and ACL repair studies could be due to the large concentration of fibrinolysis found within synovial joints. Fibrinolysis is an enzyme that degrades fibrin, a protein that is necessary for blood clot formation. With decreased blood clot formation, fewer growth factors will be secreted by the platelets participating in the clot and less growth will occur. However, when PRP is combined with collagen, a copolymer is formed that is not as susceptible to the fibrinolysis. Thus the copolymer could be beneficial in bio-enhanced repairs.

Therefore, it has been proposed that fibrin-based PRP could be combined with a collagen scaffold to create a suitable environment for ligament healing. This proposal has led to the creation of Bridge-Enhanced ACL Repair (BEAR), which stimulates the ACL to repair itself. The BEAR involves suturing a collagen scaffold to the torn ends of the ACL to form a bridge. Once in place, platelets are injected into the scaffold and a clot is formed. Slowly the torn ends of the ACL grow into the scaffold and reform the ligament (4).


A few large animal studies have demonstrated improved ACL histology and biomechanical properties in both reconstruction and repairs with the bio-enhanced repair technique (4). One study demonstrated that the bio-enhanced ACL repairs had comparable strength to ACL reconstructions at 3, 6, and 12 months post-operatively in large animals (10). Moreover, two different studies in pigs observed similar results between the ACL primary repair supplemented with collagen-platelet composite bridge and the ACL reconstruction (4). Furthermore, one of those studies, Murray and Fleming 2013 saw significantly reduced post-traumatic osteoarthritis in the bio-enhanced repair and BEAR groups in comparison to the non-treatment and reconstruction groups (Figure 2) (8).

Figure 2. Distal ends of a pig femur in four different experimental groups: ACL transection (ACLT), ACL reconstruction using patellar tendon autograft (ACLR), bridge-enhanced repair with a scaffold and autologous blood (BE-Repair), and bridge-enhanced ACL reconstruction with scaffold and autologous blood (BE-ACLR). Post-traumatic osteoarthritis can be observed at black arrows (8).


While the mechanism of the BEAR that is responsible for preventing the post-traumatic osteoarthritis is unknown, it is thought to be due to the anti-inflammatory effect of platelets (4,10). Platelets release cytokines and growth factors that increase the number of chondrocytes and enhance matrix production while it minimizes the concentration of pro-inflammatory molecules (4,8). Furthermore, it has been found that platelets decrease the overall number of cytokines within the cartilage and synovium, prevent the production of excess synovial fluid, and promote the production of proteoglycans and type II collagen. Therefore, the platelets may act to protect the chondrocytes and slow the development of post-traumatic osteoarthritis. It has also been proposed that preservation of the torn ends of the ACL may allow for the conservation of proprioception. Thus, in situations that place excessive stress on the knee, the hamstrings may be elicited to contract and dynamically protect the knee (4). This could prevent further injury to the knee joint.

Although still in development, the BEAR technique has had encouraging pre-clinical results (4,8,10). In 2014, the first-in-human study to test the BEAR procedure was approved by the FDA. In February 2015, the first BEAR was performed on a human with MRI evidence of a relatively normal ACL at 12 months post-operative (12). A small, pre-clinical trial is ongoing with 10 individuals participating in the BEAR experimental group. Thus far, all patients in the BEAR experimental group have healing ACL tissue and are on the same timeline as those repaired with an ACL reconstruction (13). A larger, second pre-clinical trial is currently accepting participants.

Despite the BEAR being a relatively new technique, the results of animal studies and the current pre-clinical trial data are promising. At this time, the BEAR is comparable to having an ACL reconstruction without some of the common issues that arise with using an autograft. However, It will take several years to determine if the BEAR is truly as effective as the ACL reconstruction and whether or not it is capable of preventing the development of post-traumatic osteoarthritis. That being said, if the BEAR is successful, it could shape the future of the ACL reconstruction and become the dominant form of treatment for ACL ruptures within the next five years.

Last revised: Ocotber 18, 2016
by Billie Weber, SPT


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2.) Monk P, Davies L, Hopewell S, et al. Surgical versus conservative interventions for treating anterior cruciate ligament injuries. Cochrane Database Sys Rev. 2016:4(CD011166). doi: 10.1002/14651858.CD011166.pub2.
3.) Neumann D. Knee. In: Neumann D. Kinesiology of the musculoskeletal system: foundations for rehabilitation. 2nd ed. St. Louis, MO: Mosby; 2010
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8.) Murray MM, Fleming BC. Use of a bioactive scaffold to stimulate ACL healing also minimizes post-traumatic osteoarthritis after surgery. Am J Sports Med. 2013;41(8):1762-1770. doi:10.1177/0363546513483446.
9.) Teuschl A, Heimel P, Nuernberger S, van Griensven M, Redl H, Nau T. A novel silk fiber-based scaffold for regeneration of the anterior cruciate ligament: histological results from a study in sheep. Am J Sports Med. 2016;44(6): 1547-1557. doi: 10.1177/0363546516631954.
10.) Proffen BL, Sieker JT, Murray M. Bio-enhanced repair of the anterior cruciate ligament. Arthroscopy. 2015;31(5):990-997. doi:10.1016/j.arthro.2014.11.016.
11.) Kopka M, Bradley J. The use of biologic agents in athletes with knee injuries. The Journal of Knee Surgery. 2016;29(5): 379-386. doi: 10.1055/s-0036-1584194.
12.) Murray M. Q+A: what you need to know about the bridge-enhanced ACL repair. Boston Children’s Hospital Web site. Published March 2016. Accessed August 19, 2016.
13.) Martha Murray, MD. Boston Children’s Hospital Web site. Accessed August 19, 2016.

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