Discovery of unexpected mechanism may help improve healing across muscle injuries

At the cellular level, the mechanics of how muscle tissue repair occurs gets complicated. There are significant differences between, say, tearing a muscle in a sports injury versus muscle tissue wasting away from diseases like muscular dystrophy.

Now, a new study led by experts at Cincinnati Children's reports finding a shared-and unexpected-mechanism that may help improve healing across several types of muscle injury.

The eye-opening study was published online Nov. 21, 2025, in Current Biology. The study was led by first author Gyanesh Tripathi, PhD, and corresponding author Michael Jankowski, PhD, who leads the Research Division at Cincinnati Children's Department of Anesthesia and is Associate Director of Basic Science Research for the Pediatric Pain Research Center.

The twist involves the role played by one immune cell type called macrophages. These white blood cells are better known as microscopic garbage trucks that engulf harmful bacteria, dead cells, and other unwanted debris.

The biggest surprise about this was finding that a macrophage has a synaptic-like property that delivers an ion to a muscle fiber to facilitate its repair after an injury. It's literally like the way a neuron works, and it's working in an extremely fast synaptic-like fashion to regulate repair."

Michael Jankowski, PhD, corresponding author

Researchers have known for some time that macrophages are involved in responding to muscle injury. They release various molecules, including cytokines and chemokines, that facilitate inflammation, affect pain sensation, and promote myofiber growth and regeneration.

Jankowski and colleagues started out looking for clues that might reduce the pain involved in post-surgery recovery. Their hope has been to find potential alternatives to existing pain medications that can come with significant side effects.

They did not find the pain-reducing clue. Instead, they found a mechanism that speeds muscle repair, which may inspire new medicines for slowing muscle wasting and helping injured people. The study also suggests that macrophages could potentially serve as another type of "delivery vehicle" for cellular therapies to treat even more conditions.

What are these macrophages up to?

"These are infiltrating macrophages, a very specific type. They're not ones already residing in the tissue. These come in after damage occurs," Jankowski says.

In a series of experiments involving mouse models of two distinct types of injury, the researchers tracked how the macrophages interacted with the myofibers that form muscle tissue. In fact, they were able to capture key moments of the activity in real time.

Using short bursts of a designer chemical to induce activation, the team watched the macrophages forming synaptic-like contacts with the myofibers. The immune cells then delivered calcium ions directly to the myofibers, which hastened an acute-injury healing process. Within 10 to 30 seconds, the researchers detected bursts of electrical activity within the affected muscles.

"This occurs in a very rapid fashion. You can activate the macrophage and make the muscle twitch subtly almost immediately," Jankowski says.

Meanwhile, the connected macrophages triggered a similar process of cell regeneration that helped mice with disease-like muscle damage. After detecting damage, the immune cells flocked to the area and induced waves of muscle fiber activity. After 10 days, treated mice showed larger numbers of new muscle fibers compared to a control group.

"A similar synaptic-like response worked in both scenarios," Jankowski says.

Next steps

More study is needed to determine if human macrophages behave the same way after muscle injury, and if so, much work would be needed to learn how to control the process in therapeutic ways.

The team also wants to learn more about one unexplained result of the work: Even though the infiltrating macrophages helped speed healing, their activity did not appear to reduce measures of acute pain sensation. Understanding more about why could help explain why about 20% of children who receive surgery experience longer term pain symptoms.

And looking forward, the researchers plan to explore more about what else a macrophage might be able to deliver to muscle cells.