During a 2018 game, Alex Smith suffered a compound fracture that broke both the tibia and fibula in his right leg. The former 49ers quarterback soon developed life‑threatening necrotizing fasciitis, a rare bacterial infection that led to sepsis and required 17 surgeries.
Muscle loss
To save his life and avoid amputation, doctors removed large amounts of muscle tissue. This caused volumetric muscle loss (VML).—a condition that overwhelms the body’s natural ability to regenerate muscle. When Smith returned to the field nearly two years later, many called his comeback a “miracle.”
Skeletal muscle is one of the body’s most dynamic tissues. It enables movement and can repair itself after injury using stem cells. But when large portions of muscle are destroyed—after severe injuries like gunshot wounds or extensive surgery—VML exceeds the regenerative capacity of muscle stem cells.
Despite how common these injuries are, no standardized way exists to assess VML, and little is known about why regeneration consistently fails. Current treatments include free muscle transfer and specialized bracing, but outcomes vary.
New Research
Now, new research from the University of Michigan may explain why traumatic muscle injuries often don’t heal.
Working with collaborators at Georgia Tech, Emory University, and the University of Oregon, U‑M scientists studied VML in mice. They found that immune cells become dysregulated after injury and interfere with stem cell repair. In non‑healing injuries, neutrophils—a type of white blood cell—remained at the injury site far longer than normal, signaling that they were not functioning correctly.
The team also discovered that communication between neutrophils and natural killer (NK) cells affected muscle stem cell–mediated repair. When neutrophils signaled to NK cells, they essentially prompted NK cells to self‑destruct.
The findings suggest that altering communication between these immune cells could change healing outcomes. This may open the door to new therapies that restore muscle function and prevent limb loss in people with VML.
The researchers hope that, with better treatments, recovery from devastating muscle injuries will no longer be considered a “miracle”—but a medical expectation.
To read the source release, click here.