Preclinical study finds earlier ACL reconstruction is associated with lower risk of knee osteoarthritis

A preclinical study by HSS 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, Ph.D., 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.”