Researchers at UAH have discovered an ultrasound-based approach that may help reduce harmful inflammation and support joint healing
Telephone line: Ross Nelson
Newswise – With an aging population experiencing joint pain and inflammation at an all-time high, researchers at the University of Alabama in Huntsville (UAH), part of the University of Alabama System, have found… New results published Which suggests that continuous low-intensity ultrasound may help shift the body’s immune response from prolonged inflammation to tissue repair, a discovery that could ultimately contribute to new treatments for joint injuries and post-traumatic osteoarthritis.
The study was published in the journal Nature Scientific reportsIt was conducted by an interdisciplinary team of researchers at UAH under the leadership of Dr. Anuradha Subramanian, professor of chemical and materials engineering. The work combined biological experiments conducted by Dr Shahid Khan as part of his PhD using computational and statistical methods developed by Dr Satyaki Roy, Professor of Mathematical Sciences, along with additional contributions from graduate student Owen Tribbiani. The research was supported by funding from the National Institutes of Health through an R01 grant awarded to Dr. Anuradha Subramanian.
The research investigates how non-invasive ultrasound affects macrophages, which are specialized immune cells that play a key role in inflammation and healing.
“After injury, the body recruits inflammatory ‘defense’ macrophages (M1) to remove damaged tissue and healing macrophages (M2) to support repair and recovery,” Subramanian explains. “The persistent dominance of defensive macrophages can create a long-term inflammatory environment that contributes to post-traumatic osteoarthritis.”
The UAH team investigated whether continuous low-intensity ultrasound could encourage macrophages to move away from this long-term inflammatory state and toward one associated with tissue repair.
“In the case of M1, microphages promote inflammation to fight damage or infection, but prolonged M1 activity can also damage healthy tissue,” Subramanian says. “In contrast, ‘M2-like’ macrophages support tissue repair and recovery. Shifting macrophages toward an M2-like state is important, because it may 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 compensatory macrophage response.”
“Post-traumatic osteoarthritis is driven in part by persistent inflammation that limits tissue repair and accelerates joint degeneration,” Roy adds. “Our team is interested in continuous low-intensity ultrasound because it offers a non-pharmacological, non-invasive approach that may help regulate immune cell behavior and promote a more reparative healing environment in affected joints.”
To better replicate what happens after a joint injury, the researchers used fibronectin fragments — molecules produced during tissue breakdown — rather than relying solely on traditional laboratory methods used to stimulate inflammation. This innovation allowed the team to create a model that closely resembles the biological environment inside the affected joint.
To support the study, Roy combined transcriptomics, a large-scale analysis of gene activity, with an advanced computational technique called differential clustering. This technique provides a way to find groups of genes that behave similarly when something changes, rather than just grouping together genes that generally look similar. Rather than examining individual genes separately, this approach allowed the researchers to identify coordinated changes across groups of genes, providing a broader view 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 ultrasound stimulation,” says Roy.
Results showed that continuous low-intensity ultrasound reduced markers associated with inflammation while increasing markers associated with a more compensated M2-like macrophage state.
While the work is still in the laboratory research phase, the results highlight the potential of non-pharmacological and non-surgical techniques to influence immune behavior and support recovery after infection. The researchers believe this approach could ultimately complement future treatments aimed at slowing the progression of osteoarthritis and improving healing after joint trauma.
“Next steps will include validating these findings in animal models of post-traumatic osteoarthritis and studying how ultrasound-based modulation affects long-term tissue repair in cases of joint injury,” Subramanian says.
