The 2022 Orthopaedic Research and Education Foundation (OREF) Clinical Research Award was presented to Martha Murray, MD, FAAOS, and her collaborators for outstanding clinical research related to musculoskeletal disease or injury. Dr. Murray and her colleagues studied techniques to restore the anterior cruciate ligament (ACL) after a tear, leading to FDA de novo 510(k) approval in December 2020 of the bridge-enhanced ACL restoration (BEAR) implant, the first implant to stimulate ACL healing. The research team previously won the Kappa Delta Ann Doner Vaughn Award in 2013 for the preclinical work leading to the proof of concept of the BEAR implant.
“Our hypothesis was that restoring, rather than replacing, the ACL would have some inherent advantages, including keeping the muscles and tendons around the knee intact, leading to less pain and weakness,” said Dr. Murray, orthopaedic surgeon-in-chief of the Orthopedic Center at Boston Children’s Hospital and professor of orthopaedic surgery at Harvard Medical School. “However, all of those advantages would not be enough if the knee wasn’t stable or the knee didn’t feel right to the patient with the BEAR implant as compared to the current gold standard of ACL reconstruction.”
How the BEAR implant works
In most tissue injuries, such as the medial collateral ligament, blood pools and clots in the tear site, connecting the two ligament ends. Tissue can then grow into that provisional scaffold and heal the injury. However, this doesn’t happen in ACL injuries. When an ACL is injured, a blood clot doesn’t form at the injury site, most likely due to synovial fluid (a thick liquid found within the joint) washing out the clot. The researchers determined that the absence of the provisional scaffold in the ACL was the key reason it fails to heal.
Working with her colleagues, Dr. Murray utilized an extracellular matrix (ECM) that could be manufactured into a porous implant that serves as a substitute scaffold and absorbs and holds the blood in the ACL tear site. The BEAR implant is secured by a suture to connect the ends of the torn ACL and then saturated with the patient’s blood to allow a clot to form and eventually reunite the ligament.
Moving to human trials
After researchers demonstrated that the biomechanical outcomes were equivalent to those of ACL reconstruction in preclinical trials, the first human clinical trial was set up to evaluate patient safety.
Two 10-patient cohorts were established, with initial follow-up at three months postoperatively to assess infection rates, inflammation requiring medical intervention, reoperation, and other adverse events.
Patients with a complete, midsubstance ACL tear received either the BEAR implant or autograft ACL reconstruction. At the three-month mark, no patients had joint infections or signs of significant inflammation. Both groups had similar pain scores, knee swelling, and opioid pain medication requirements. No BEAR implants needed to be removed and no arthrofibrosis was seen in the BEAR implant group. Hamstring strength was significantly better in the BEAR implant group.
At the two-year mark, there were no failures in either group. BEAR implant patients reported an average score of 92 and graft patients reported an average score of 85 on the International Knee Documentation Committee (IKDC) subjective scores, a patient-reported outcome measure. Hamstring strength remained higher in the BEAR implant group compared to the ACL reconstruction group. Two years postoperatively, the BEAR implant produced equivalent or better outcomes to ACL reconstruction and further research could continue.
BEAR II trial leads to FDA approval
In a randomized, controlled trial of 100 patients (median age, 17 years) with a complete ACL tear, 65 patients were randomized to the BEAR implant group and 35 patients to the control group to receive an autograft ACL reconstruction. All patients received physical therapy and were followed for two years.
Two years postoperatively, 99 percent of the patients were able to be assessed for follow-up. Both patient groups had similar IKDC scores (average of 89 for BEAR implant patients and average of 85 for ACL reconstruction patients). Arthrometer testing to measure differences in knee laxity between the healthy knee and the injured knee showed comparable anterior-posterior laxity between the two techniques. Patients who had the BEAR implant had significantly higher mean hamstring muscle strength indices than the patients in the ACL reconstruction group.
High reinjury rates in active adolescents are an issue following ACL reconstruction, with revisions rates ranging from 10 percent to 28 percent. For adolescents who undergo a simple suture repair, the risk for reinjury is even higher, at almost 50 percent after three years. The BEAR implant group had a revision rate of 14 percent, which is lower than the suture repair rate and similar to ACL reconstruction rates.
“The study showed that the hamstring strength in patients was significantly better, which is very important to patients,” said Dr. Murray. “Any time you take a graft from another part of the body, that graft site can be painful and then the knee still doesn’t feel quite right. With the BEAR implant, patients felt their knee return to normal more quickly. By doing a double-blinded, randomized, controlled trial, orthopaedic surgeons now have a better understanding of the outcomes they can expect for their patients. These data will help surgeons and patients make an informed decision on what procedure is right for them.”
- Gagliardi AG, Carry PM, Parikh HB, Traver JL, Howell DR, Albright JC: ACL repair with suture ligament augmentation is associated with a high failure rate among adolescent patients. Am J Sports Med. 2019;47(3):560-6.