In what is surely the best use of pig bladders since the invention of the football, researchers have used a scaffold derived from pig bladder extracellular matrix to mobilize muscle stem cells and regrow large amounts of muscles that had been lost in wounds.

The findings open up new therapeutic possibilities for patients who have lost such large amounts of muscle that the body's natural repair capacities cannot replace them, a condition known as volumetric muscle loss.

Smaller muscle wounds can be repaired by the body with relative ease. But, senior author Stephen Badylak told reporters at a press conference, "when you lose so much muscle that the gap is too large for the normal restorative process to occur, the end result is typically filling that gap with scar tissue," which leads to a marked loss of function.

All five patients described in the paper, which appeared in the May 1, 2014, issue of Science Translational Medicine, had such extensive loss of function despite having multiple surgeries and extensive physical therapy. In some cases, the loss of function of the affected limb had been bad enough for the patients – some of whom were military personnel who had been injured by IEDs, while others were civilians who had suffered accidents – to consider amputation.

"The things that you and I take for granted, getting out of a chair, taking steps, stepping off a curb, getting out of a car, these are the types of deficits that these individuals had," Badylak said. "Frankly, most of these patients have been through hell."

Sometimes, muscles can be transplanted, or tendons rerouted, to have existing muscles take over the functions of lost ones. But that often amounts to robbing Peter to pay Paul. "You are removing function from another part of the body, and once you move that muscle, the growth of the nerves is not always satisfactory," co-author Peter Rubin said told reporters.

Strategies aimed at producing new muscle tissues have been based on cell delivery. But first author Brian Sicari succinctly summed up the key sticking point to that approach.

"Where do you get the cells?"

So in their work, Badylak and his colleagues, who are at the University of Pittsburgh, used a different approach instead: They mobilized the body's own muscle stem cells through the use of a scaffold made out of pig bladder.

The scaffold essentially drew out the body's own stem cells, which repopulated the scaffold with enough muscle cells to close large gaps and, in several cases, improve functional outcomes.

Using an approach that contains no cells has advantages that range from the clinical to the regulatory, Badylak said.

On the clinical side, the patients do not need to be permanently immunosuppressed as organ recipients do because although the recipient immune system does recognize the implants as foreign, "the recognition that occurs is not only not destructive, it's actually beneficial. . . . You want the recipient to recognize it, because the signals that are transmitted are constructive signals to the immune system. There is recognition, but it's a friendly recognition rather than a destructive recognition."

And on the regulatory side, "when you've got an approach that does not involve the delivery of cells, that greatly simplifies regulatory hurdles that need to be overcome, and also the cost of the therapy."

To make sure that the effects they observed were not natural long-term improvements, the authors tested their scaffold on patients who had been injured at least six months before entering the study. In practice, all of the injuries were at least a year old, with the oldest being more than seven years in the past.

If the patients had been treated soon after sustaining their injuries "which is certainly possible and may even be preferable," Badylak said – it would not have been possible to say how much improvement would have occurred without the treatment.

The researchers also made sure their observed results were due to the surgery by first treating them with an intense regimen of physical therapy tailored to their injury. Only when the patients showed no further improvement in response to ongoing physical therapy did they implant them with the matrix.

Using this protocol, three out of five patients improved after surgery, though Badylak said that the other two failed only because they did not show improvement on every one of the criteria the researchers had established. "By the rules we established going into the study, we had to technically call them failures," he said. But "these patients will tell you that they're better."