Injury is a sad fact of military service, especially in wartime. According to a study performed by scientists at the Uniformed Services University of the Health Sciences, by far the most frequent is soft tissue injuries to skin, fat and muscle.
Of these, muscle damage is particularly difficult to heal. Beyond a certain size—about one cubic centimeter—the body simply cannot do it. As a result, people experiencing this kind of trauma, called volumetric muscle loss, lose function of the muscle, and experience deformation, scar tissue or contracted muscles.
According to a study from 2015 in the Journal of Rehabilitation Research and Development (a peer-reviewed publication put out by the Department of Veterans Affairs), volumetric muscle loss is typically permanent.
“The current primary standard of care for [volumetric muscle loss] injuries is physical rehabilitation,” says Benjamin Corona, lead author of the study. “The documented cases available do not indicate significant functional recovery unless energy returning orthoses [braces or other devices] are used. Physical rehabilitation alone will not promote regeneration of the lost tissue.”
Corona and his team of researchers looked at the records of more than 500 service members who were discharged from the military due to injuries between 2001 and 2007. They found that most broken bones sustained in combat result in open wounds, and that while the bone can often be repaired, the muscle is left damaged. Service members who sustained broken bones are often disqualified from service not because of the break, but because of disability due to the soft-tissue wound.
“Despite a tremendous amount of attention given to bone healing after type III open tibia fracture, based on the current findings it is appropriate to conclude that soft-tissue complications make the majority contribution to disability of salvaged limbs,” the authors wrote. “The development of therapies addressing [volumetric muscle loss] has the potential to fill a significant void in orthopedic care.”
Historically, the best course of treatment was to use a flap of muscle, either from a different part of the body or rotated from a connected muscle, to cover the wound. This helps to heal, but cannot provide the normal use of an uninjured muscle, and so the limb where the injury occurred is often permanently disabled.
“There have been a lot of attempts to replace lost muscle,” says Li Ting Huang, a staff scientist at Acelity, a biotech company that provides regenerative technology to the Department of Defense. “Those [muscle flap transfers] generally don’t work too well, because for a muscle to function it needs the enervation, it needs to have nerves running through it. So you need to kind of reconnect all of the nerves and blood vessels as well, to keep the implanted muscle alive and functioning. This is something that is very difficult to do.”
Huang is leading a new muscle regeneration technology project, which aims to modify the company’s existing technology to solve volumetric muscle loss.
“The main thing is, obviously there’s the large unmet clinical need for a product like this, especially for the patient population that we’re looking at, for military servicemen and women,” says Huang.
Acelity rebranded a couple of years ago, but its core businesses are in wound regeneration, and its products can be found in military and veteran’s hospitals, as well as public ones, and even in war zones. Primarily, they include negative pressure wound therapy (which draws out fluid and brings blood to the wound), webs of organic material called tissue matrices for skin wound recovery, and a preservation solution that keeps the tissue matrices viable for up to two years.
Those matrices are what Huang is jumping off from as she builds her muscle regeneration technology.
She starts with a pig muscle, and uses a proprietary process that strips the tissue of all cell components, which can cause inflammation or even be rejected by the body. The resulting material, called an acellular muscle matrix, looks eerily like real muscle, complete with texture and fibers, except it is pale and almost translucent.
Then, the matrix is surgically implanted, taking care to align it to match the existing tissue. With rehabilitation and therapy to help the existing muscle tissue grow, Huang argues it can mend the muscle back together.
A more recent paper in Biomaterials by Corona examines the use of acellular matrices in healing volumetric muscle loss. His conclusion is less rosy, concluding that while muscle recovery occurs, it is not to such a degree as to offer the power needed for the muscle to operate. “The existing data do not support the capacity of acellular biological scaffolds to promote a physiologically meaningful volume of skeletal muscle tissue,” Corona and co-author Sarah Greising wrote. That said, they add that “acellular biological scaffolds remain a vital tool for VML repair that should continue to be developed in conjunction with other biomaterial, biological, and rehabilitative therapeutic strategies.”
Huang says she has gotten the process to work in rats. Next comes larger animals, and she isn’t keen to speculate farther than that, though she says she is working to expand the size of the matrices, which were originally about six centimeters square.
“Personally, for me, this project has been one of the most satisfying projects I’ve worked on,” she says. “Especially since it can help a patient population that has sacrificed so much for our country.”