Hospital for Special Surgery Preclinical Study Finds Earlier ACL Reconstruction is Associated with Lower Risk of Knee Osteoarthritis

A preclinical study by HSS (Hospital for Special Surgery) investigators found that earlier anterior cruciate ligament (ACL) reconstruction led to lower immune cell activity, less inflammation and fewer joint changes associated with knee osteoarthritis compared to delayed surgery. The research team shared their study results today in a poster presentation at the American Academy of Orthopaedic Surgeons 2025 Annual Meeting.

After a knee injury, such as an ACL tear or rupture, immune cells travel to lymph nodes, where they interact with other cells that support and regulate inflammatory responses in the joint. This activity plays a critical role in healing, but prolonged immune cell activity and inflammation can promote osteoarthritis.

“Orthopedic surgeons actively debate the optimal timing of ACL reconstruction after an ACL injury,” says senior study author Scott Rodeo, MD, Vice Chair of Orthopaedic Research, co-director of the Orthopaedic Soft Tissue Research Program, and director of the Center for Regenerative Medicine at HSS. “The original thought for delaying surgery was to let inflammation resolve since operating on a highly inflamed knee can lead to postoperative stiffness, but how long to wait has been unclear.”

Dr. Rodeo and the HSS research team, including Theresa T. Lu, MD, PhD, St. Giles Chair for Research in the HSS Research Institute and pediatric rheumatologist, investigated the timing question in preclinical models of ACL reconstruction. In total, 16 models underwent immediate reconstruction after ACL rupture, 16 underwent surgery a week after injury, and 16 had no surgery. After four weeks, the researchers used advanced techniques to identify and measure the number of immune cells present in the spleen and iliac lymph nodes that drain from the knee.

The researchers observed an increase in several immune cell populations in the two surgical groups compared to the no-surgery group. Immune cell counts were significantly higher in the group that had delayed surgery compared to the group that underwent immediate surgery.

The investigators also assessed cartilage changes associated with osteoarthritis in the preclinical models. The group that had delayed surgery showed more severe and extensive signs of cartilage destruction than the group that had immediate surgery.

“Overall, our preclinical study suggests that immediate ACL reconstruction may lower the risk of developing knee arthritis, tying in with existing studies showing that chronic, unresolved inflammation leads to progressive arthritis after knee injury,” Dr. Rodeo says. “These results inform ongoing human studies at HSS in which we are evaluating the optimal timing of surgery and other factors that affect the role of immune cells and inflammatory responses in ligament healing. In these studies, we are evaluating changes in immune cells and inflammation in lymph nodes using magnetic resonance imaging, joint fluids and blood.”

Authors: Thomas M. Li, MD, Julia Retzky, MD, Camila Carballo, PhD, PT, Jihyun Sim, Lauren E. Simonian, BS, Mohammed Hammad, MD, Yuki Okazaki, MD, PhD, Claire Eliasberg, MD, Theresa T. Lu, MD, PhD, Scott A. Rodeo, MD, FAAOS.

Reference:

¹ Li TM, Retzky J, Carballo C, Sim J, Simonian LE, Hammad M, Okazaki Y, Eliasberg C, Lu TT, Rodeo SA. Early anterior cruciate ligament reconstruction in a murine model is associated with reduced local lymph node responses. Accessed February 10, 2025 at https://submissions.mirasmart.com/AAOS2025/Itinerary/PresentationDetail.aspx?evdid=428

About HSS

HSS is the world’s leading academic medical center focused on musculoskeletal health. At its core is Hospital for Special Surgery, nationally ranked No. 1 in orthopedics (for the 15th consecutive year), No. 3 in rheumatology by U.S. News & World Report (2024-2025), and the best pediatric orthopedic hospital in NY, NJ and CT by U.S. News & World Report “Best Children’s Hospitals” list (2024-2025). In a survey of medical professionals in more than 20 countries by Newsweek, HSS is ranked world #1 in orthopedics for a fifth consecutive year (2025). Founded in 1863, the Hospital has the lowest readmission rates in the nation for orthopedics, and among the lowest infection and complication rates. HSS was the first in New York State to receive Magnet Recognition for Excellence in Nursing Service from the American Nurses Credentialing Center five consecutive times. An affiliate of Weill Cornell Medical College, HSS has a main campus in New York City and facilities in New Jersey, Connecticut and in the Long Island and Westchester County regions of New York State, as well as in Florida. In addition to patient care, HSS leads the field in research, innovation and education. The HSS Research Institute comprises 20 laboratories and 300 staff members focused on leading the advancement of musculoskeletal health through prevention of degeneration, tissue repair and tissue regeneration. In addition, more than 200 HSS clinical investigators are working to improve patient outcomes through better ways to prevent, diagnose, and treat orthopedic, rheumatic and musculoskeletal diseases. The HSS Innovation Institute works to realize the potential of new drugs, therapeutics and devices. The HSS Education Institute is a trusted leader in advancing musculoskeletal knowledge and research for physicians, nurses, allied health professionals, academic trainees, and consumers in more than 165 countries. The institution is collaborating with medical centers and other organizations to advance the quality and value of musculoskeletal care and to make world-class HSS care more widely accessible nationally and internationally. www.hss.edu.

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