ACL injuries occur at a high frequency in the US with approximately 400,000 ACL reconstructions being performed each year in the US. The anterior cruciate ligament is a major stabilizer of the knee joint and courses through the middle of the joint. Injuries of the ACL do not heal spontaneously, and suture repair of these injuries has been shown to have a high failure rate (over 90%). Thus, suture repair has been abandoned in favor of ACL reconstruction, where the injured ACL is removed and replaced with a tendon graft. While ACL reconstruction is a good operation for restoring gross knee stability, it does not restore joint motion, or prevent the premature development of osteoarthritis in many patients.Current data suggests that 76% of patients with an ACL tear will develop osteoarthritis at only 14 years from injury -- whether they have an ACL reconstruction or not. Thus, new treatments for an ACL injury, which are less invasive and have the potential to minimize patient morbidity, are highly desirable. Bio-enhanced ACL repair, using a tissue engineered approach to stimulate healing, is one such strategy.
Our work has focused on new ways to treat ACL injury to try to improve patient outcomes. We wondered if outcomes would be better if we encouraged the ACL to heal, rather than replacing it. To make this work, we would need to find out why it doesn’t heal naturally. Through a series of studies, we compared ligaments that do heal (like the medial collateral ligament of the knee) with ligaments that don’t (like the ACL) to find out where the differences lie. We found that when the MCL tears, a blood clot forms between the torn tissue ends and serves as a bridge for the tissue to heal back into. However, for the ACL, the joint fluid prevented the blood from forming a solid clot, so there was no structure rejoining the two ends of the ligament, and no structure for the torn ends to heal into.
We hypothesized that this was the major reason the ACL wouldn’t heal on its own. We worked on developing a scaffold that we could place between the two torn ends of the tissue to use as a substitute bridge. After trying multiple materials, we found a protein-based scaffold that would work. We tried adding different growth factors to the scaffold and found that in the end, the blood that forms the scaffold in other tissues is actually the best biologic agent for stimulating ACL healing as well. The new technique involved taking the protein scaffold and loading it with a few cc's of blood and placing it in between the torn ends of the ACL. The scaffold would make the blood clot and hold it in place long enough for the ACL to heal.
When we tried this in a preclinical model, we found that the strength of the healing ligament was similar in the knees treated with repair and those treated with reconstruction. When we then looked at what happened at one year after surgery, we found that the strengths of the two techniques were not statistically different, and the knees treated with a bioenhanced repair had less arthritis than those treated with a reconstruction.
If these same results hold up in human trials, we will have developed a less-invasive and improved method for treating patients with ACL tears. Functional healing of the torn ACL using a bio-enhanced repair technique could significantly impact treatment of hundreds of thousands of patients each year in the US alone. The immediate benefits for the patient would be a far less invasive surgical procedure that ACL reconstruction as no graft harvest is required. The long-term benefits for patients are potentially even greater, as retention of the proprioceptive nerve fibers in the ACL, complex anatomy of the insertion sites and fan shape of the ligament will more closely restore the normal dynamic biomechanics of the knee and thus is likely to decrease the premature osteoarthritis seen in the knees of patients after an ACL tear. With the successful completion of our ongoing translational studies guided by the FDA to make sure the technique is as safe as possible to try in human patients, we will be positioned to begin clinical trials of this novel approach to treat ACL injuries.
About Martha Murray
Martha Murray received her master's degree in materials science and engineering from Stanford University and her medical degree from the University of Pennsylvania. She completed a residency in orthopedic surgery at Harvard Medical School and fellowships in pediatric orthopedics and sports medicine at Boston Children's Hospital.
Dr. Murray also specializes in the clinical care and surgical treatment of patients with knee injuries, including injuries of the ACL, meniscus, and cartilage. If you would like to schedule an appointment, please call 617-355-3501.
- The ACL Handbook: Knee Biology, Mechanics, and Treatment. Murray MM, Vavken P, Fleming BC. Springer, 2013.
- The effect of skeletal maturity on functional healing of the anterior cruciate ligament. Murray, MM, Magarian, EM, Harrison, SL, Zurakowski, D, and Fleming, BC. J Bone Joint Surg Am, 2010 Nov;92(11):2039-49.
- Activation by collagen provides sustained release of anabolic cytokines. Harrison, S, Vavken, P, Kevy, S, Jacobson, M, Zurakowski, D, and Murray, MM. Platelet Am J Sports Med. 2011 39(4):729-34.
- Reduced platelet concentration does not harm PRP effectiveness for ACL repair in a porcine in vivo model. Mastrangelo AN, Vavken P, Fleming BC, Harrison SH, and Murray, MM. J Ortho Res, 2011 Jul;29(7):1002-7.
- Biomechanical outcomes after bio-enhanced anterior cruciate ligament repair and anterior cruciate ligament reconstruction are equal in a porcine model. Vavken, P, Fleming, BC, Mastrangelo, AN, Machan, JT, Murray, MM. Arthroscopy, 2012 May;28(5):672-80.
- In situ non-invasive T2*-weighted MRI derived parameters determine ex vivo structural properties of an ACL reconstruction or bio-enhanced primary repair in a porcine model. Biercevicz, A, Miranda, DL., Machan, JT, Murray, MM, Fleming, BC. Am J Sports Med. 2013 Jan 24.
Dr. Murray's Curriculum vitae
Articles on PubMed.org authored or co-authored by Dr. Murray.