A University of Wisconsin–Madison spinoff that makes an innovative material designed to speed healing of serious burns has begun a large clinical trial for the “regenerative skin tissue” it has been developing since 2000.

Stratatech, now a Mallinckrodt Pharmaceuticals company, aims to prove to the Food and Drug Administration that the material, called StrataGraft, is safe and effective for treating severe burns. Intense burns can be painful, even deadly, because they destroy key protections against infection and dehydration.

Today, treatment involves removing a portion of the patient’s intact skin and grafting it to the burned site. In contrast, StrataGraft is designed to cover deep burns with a matrix containing human skin cells.

These cells, called keratinocyte progenitors, are able to form the epidermis, or top layers of skin. It is possible that the progenitor cells also produce and release growth factors that stimulate regeneration of the patient’s own skin cells, yet evoke a very limited immune response.

In 2015, after its second clinical trial, Stratatech announced that StrataGraft had fully closed deep, partial–thickness burns on 27 of 28 patients in three months.

In August 2016, Stratatech was purchased by Mallinckrodt Pharmaceuticals of the United Kingdom.

Allen–Hoffmann is on leave from her position as professor of pathology and surgery at UW–Madison’s School of Medicine and Public Health.

StrataGraft has completed two rounds of clinical trials. The make–or–break phase three trial that has now started will be performed over several years at multiple sites nationally. The product is based on certain unique cells that appeared in Allen–Hoffmann’s lab in the late 1990s. After her technician, Sandy Schlosser, pointed them out, “I can distinctly remember saying, as I was sitting at the microscope, ‘I think this colony of keratinocytes looks amazingly basal,’” Allen–Hoffmann recalls. Although the cells had an extraordinary ability to survive in culture, they were not malignant.

“It was fascinating,” she says. “When cultured appropriately, they can recapitulate the 3–D architecture of skin tissue. They made a wonderful model system for research on skin biology.”

In 2007 StrataGraft’s potential appeared with the first human patient. Within a week or so, Allen–Hoffmann says, “the surgeon called to say the material had become adherent to the wound bed, there was no acute immune response, and it was ‘pinking up,’ indicating a new blood supply. ‘Why don’t we leave it on, it’s looking good.’”

For the sake of caution, the trial required removal of the skin substitute after seven to 10 days, but the first results were no fluke. StrataGraft was left in place in subsequent studies, and even though it was getting a blood supply, the DNA of the implanted cells was not found in patients after three months.

As it stands now, StrataGraft is being investigated to see how it adheres to the wound to protect against infection and dehydration. Then, like normal skin, it falls off. “This is not inconsistent with how our skin functions in life,” Allen–Hoffmann says. “The cells differentiate, move up, and ultimately fall off the body.”

Tests to date have compared StrataGraft to the current standard of care, called autografting. This skin graft transfer of the patient’s healthy skin does cover the burn site, but it creates additional wounds that are painful and subject to infection, and the results are inconsistent.

“The whole goal in these proof–of–concept studies was to remove less uninjured skin, thereby avoiding yet another painful wound,” Allen–Hoffmann says. “So we have shown that we could treat individuals who would have required autografts. We are now in a phase three clinical trial for StrataGraft, with a larger patient population than earlier trials,