Researchers at the University of Alabama in Huntsville (UAH), part of the University of Alabama System, have identified a promising new use for low-intensity continuous ultrasound that could one day help treat joint injuries and reduce the risk of post-traumatic osteoarthritis. Their findings suggest that the non-invasive approach may divert the body’s immune response from long-lasting inflammation toward tissue repair, offering a potential drug-free strategy to enhance healing.
The study, published in the journal Nature Scientific Reportswas led by Dr. Anuradha Subramanian, professor of chemical and materials engineering. It combined biological research conducted by Dr. Shahid Khan during his doctoral studies with computational and statistical analysis developed by Dr. Satyaki Roy, professor of mathematical sciences, along with contributions from graduate student Owen Trippany. The research was funded by the National Institutes of Health through an R01 grant awarded to Subramanian.
How ultrasound influences immune cells
The team focused on macrophages, specialized immune cells that play a key role in both inflammation and tissue repair, to understand how they respond to continuous low-intensity ultrasound.
“After an injury, the body recruits inflammatory ‘defending’ macrophages (M1) to clear damaged tissue and healing macrophages (M2) to support repair and recovery,” explains Subramanian. “Persistent dominance of defender macrophages may create a prolonged inflammatory environment that contributes to post-traumatic osteoarthritis.”
The researchers wanted to determine if ultrasound could stimulate these immune cells to shift from an inflammatory state to one that promotes healing.
“In an ‘M1’ state, microphages promote inflammation to fight damage or infection, but prolonged M1 activity can also damage healthy tissue,” Subramanian notes. “In contrast, ‘M2-like’ macrophages support tissue repair and recovery. Shifting macrophages toward an M2-like state is important because it can help reduce chronic inflammation while promoting healing in damaged joints. Our findings suggest that continuous low-intensity ultrasound may help restore this balance by promoting a more reparative macrophage response.”
Roy says chronic inflammation is a major factor in the development of post-traumatic osteoarthritis.
“Post-traumatic osteoarthritis is due in part to persistent inflammation that limits tissue repair and accelerates joint degeneration,” adds Roy. “Our team is interested in low-intensity continuous ultrasound because it offers a non-pharmacological, non-invasive approach that can help regulate the behavior of immune cells and promote a more restorative healing environment in injured joints.”
A more realistic model of joint injury
To better recreate the conditions within an injured joint, the researchers relied on fragments of fibronectin, molecules generated as damaged tissue breaks down, rather than using only conventional laboratory methods to trigger inflammation. This approach produced a model that more closely reflects the biological environment that develops after joint injury.
The team also combined transcriptomics, the large-scale study of gene activity, with an advanced computational method known as differential clustering. Instead of analyzing genes one by one, this technique identifies groups of genes whose behavior changes together, providing a broader picture of how immune cells respond to ultrasound treatment.
“This allowed us to study not only which genes changed, but also how groups of genes changed their coordinated behavior in response to ultrasonic stimulation,” says Roy.
First results show a reduction in inflammation
The researchers found that continuous low-intensity ultrasound reduced biomarkers related to inflammation, while increasing markers associated with a more restorative macrophage state, similar to M2.
Although research is still limited to laboratory experiments, the findings suggest that non-invasive, drug-free technologies could eventually be used to influence the behavior of immune cells and improve healing after joint injuries. Researchers believe the technique could be part of future treatments designed to slow the progression of osteoarthritis and improve recovery after joint trauma.
“Next steps will involve validating these findings in animal models of early post-traumatic osteoarthritis and studying how ultrasound-based modulation affects long-term tissue repair in joint injury settings,” says Subramanian.