Regenerative Medicine Improves Muscle Strength, Function in Leg Injuries

Damaged leg muscles grew stronger and showed signs of regeneration in three out of five men whose old injuries were surgically implanted with material derived from a pig bladder, according to a new study conducted by researchers at the University of Pittsburgh School of Medicine and the McGowan Institute for Regenerative Medicine. Early findings from a human trial of the process and from animal studies were published recently in Science Translational Medicine.

“This new study is the first to show replacement of new functional muscle tissue in humans, and we’re very excited by its potential,” senior investigator Stephen F. Badylak said. “These are patients who can’t walk anymore, can’t get out of a car, can’t get up and down from a chair, can’t take steps without falling. Now we might have a way of helping them get better.”

When a large volume of muscle is lost, typically due to trauma, the body cannot sufficiently respond to replace it, explained Badylak, a Pitt professor of surgery and deputy director of the McGowan Institute, a joint effort of Pitt and UPMC. Instead, scar tissue can form, significantly impairing the muscle’s strength and function.

The pig bladder material, known as the extracellular matrix, is the non-cellular biologic scaffold that remains after cells have been removed from the pig bladder. For many years, the material has served as the base for medical products used to repair hernias and treat skin ulcers. Earlier research by Badylak’s team suggested that the extracellular matrix also could be used to regenerate lost muscle by placing the material in the injury site. Once there, it signals the body to recruit stem and other progenitor cells to rebuild healthy tissue.

In the study, Pitt researchers observed five men who, at least half a year earlier, had lost a minimum of 25 percent of leg muscle volume and function—compared to the uninjured limb. The participants underwent a customized regimen of physical therapy for 12 to 26 weeks until their function and strength plateaued for a minimum of two weeks.

Then, the study’s lead surgeon, J. Peter Rubin, surgically implanted a “quilt” of compressed extracellular matrix sheets designed to fill into their injury sites. Within 48 hours of the operation, the participants resumed physical therapy for as much as 26 additional weeks.

The researchers found that, six months after the surgery, three of the participants, two of whom had thigh injuries and one a calf injury, were stronger by 20 percent or more. One thigh-injured patient improved on the “single hop test” by 1,820 percent, another had a 352 percent improvement in a chair lift test and a 417 percent improvement in the single-leg squat test. Biopsies and scans all indicated that muscle growth had occurred. Two other participants with calf injuries did not have such dramatic results, but both improved on at least one functional measure and said they felt better.

“This work represents an important step forward in our ability to repair tissues and improve function with materials derived from natural proteins. There will be more options to help our patients,” said Rubin, who is UPMC Endowed Professor and chair of Pitt’s Department of Plastic Surgery as well as a professor of bioengineering at the University.

The study also showed that six months after an injury, mice treated with extracellular matrices showed signs of new muscle growth, while untreated mice appeared to form typical scars.

The research is being conducted as part of the Muscle Tendon Tissue Unit Repair and Reinforcement Reconstructive Surgery Research Study, which is sponsored by the U.S. Department of Defense and is continuing to enroll new participants.