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A new preclinical study from Hospital for Special Surgery (HSS) has shed light on the potential benefits of early anterior cruciate ligament (ACL) reconstruction. According to the research team, conducting ACL surgery sooner rather than later leads to significantly lower immune cell activity, less inflammation, and reduced joint damage associated with knee osteoarthritis. These results, presented today at the American Academy of Orthopaedic Surgeons (AAOS) 2025 Annual Meeting, could have important implications for the timing of ACL surgeries in patients.
The Role of Immune Cells in ACL Healing and Osteoarthritis
When a knee injury occurs, such as an ACL rupture, immune cells are activated and travel to the lymph nodes. There, they interact with other cells that help regulate the body’s inflammatory responses in the joint. While this immune response is critical for healing, prolonged or chronic inflammation can increase the risk of developing osteoarthritis. The researchers at HSS, led by Dr. Rodeo, aimed to investigate whether the timing of ACL reconstruction surgery plays a role in managing these immune responses and, consequently, the risk of osteoarthritis.
Study Design and Findings
The HSS research team, which included Dr. Theresa T. Lu, MD, PhD, and pediatric rheumatologist, conducted a preclinical study with 48 animal models to assess the impact of early versus delayed ACL reconstruction. The models were divided into three groups:
- Group 1: Immediate ACL reconstruction after injury (16 models)
- Group 2: Surgery one week after injury (16 models)
- Group 3: No surgery (16 models)
After four weeks, the researchers analyzed the immune cell populations in the spleen and iliac lymph nodes, which drain from the knee, using advanced techniques. The results showed that the immune cell counts were significantly higher in both surgical groups compared to the no-surgery group. Notably, the delayed surgery group had significantly more immune cell activity than the immediate surgery group.
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Cartilage Changes and Osteoarthritis Development
In addition to assessing immune response, the team examined the cartilage in the knee joints for signs of osteoarthritis. They found that the delayed surgery group exhibited more severe and widespread cartilage damage compared to the immediate surgery group. This suggests that waiting too long to reconstruct the ACL may increase the risk of long-term joint destruction.
Implications for ACL Surgery Timing
Dr. Rodeo emphasized the broader implications of these findings, suggesting that early ACL reconstruction may help reduce the risk of developing knee arthritis. He pointed out that chronic, unresolved inflammation is known to contribute to progressive arthritis following a knee injury, aligning with previous studies that have explored the importance of timely surgical intervention.
“Immediate ACL reconstruction could potentially reduce the inflammatory response and prevent the cartilage damage that often leads to osteoarthritis,” said Dr. Rodeo. “This study is a step forward in understanding the relationship between immune responses, inflammation, and the long-term health of the knee joint.”
Ongoing Human Studies at HSS
Building on these promising preclinical results, HSS is currently conducting human studies to further explore the optimal timing for ACL surgery and its effect on immune responses and inflammation. These studies include innovative approaches such as using magnetic resonance imaging (MRI) and analyzing joint fluid and blood to better understand how these factors contribute to ligament healing and the risk of osteoarthritis.
By exploring these critical variables, the research team at HSS hopes to refine surgical guidelines that could ultimately lead to better long-term outcomes for ACL injury patients.
