Madison-based Stratatech, a privately held regenerative medicine company, has genetically modified its StrataGraft living human skin substitute to actively fight costly bacterial infections that routinely develop at the site of burns and other severe skin injuries, such as skin ulcers.

Stratatech’s StrataGraft tissue is a second-generation human skin substitute that exhibits normal human skin structure and function. It is manufactured using the company’s proprietary NIKS human keratinocytes, which were discovered at the University of Wisconsin. Keratinocytes are the cells that make up approximately 90 percent of the epidermis or outer layer of the human skin. NIKS cells are a consistent source of pathogen-free, non-tumor producing, long-lived adult progenitor cells. These cells faithfully reproduce normal human skin tissue architecture and barrier function when cultured appropriately.

The addition of the ability to proactively fight bacterial infection is a discovery with long-reaching implications. Bacterial infection is a primary cause of skin graft rejection and can significantly increase the hospital cost of burn and other skin injury patients.

The major method for controlling bacterial infections is through the use of antibiotics; however antibacterial resistance has become, and is continuing to grow, as a major public health concern.

In contrast, Stratatech’s new genetically engineered tissue, called ExpressGraft Enhance skin substitute, enables the immediate topical delivery of a potent anti-infective that actively inhibits bacterial growth and promotes re-growth of the patient’s own cells. The skin substitute was tested against A. baumannii, a pathogenic, multi-drug-resistant bacterium responsible for an increasing number of virulent hospital-acquired infections.

The antibiotic resistance of A. baumannii and other bacteria is a major challenge in the treatment of burns and other skin injuries, not just in the United States, but around the world. Bacterial infection is a major obstacle to wound healing and the primary reason for short-term skin graft failure. A 2004 U.S.-based study found that burn patients infected with A. baumannii had average hospital costs of nearly $100,000 more than uninfected patients with similar burns.

Stratatech’s skin substitute was also generated using a non-viral sector or carrier. The company believes this is the first time a virus-free approach has been used to genetically modify a living, cell-based tissue substitute.

According to data published online in the medical journal Molecular Therapy, Stratatech’s modified tissue contained 139-fold more anti-infective proteins, called host defense peptides, than unmodified tissue in vitro.
An in vivo model of an infected, third-degree burn also was used to assess the bacteria-fighting ability of the genetically engineered tissue. The study showed that the modified tissue reduced the growth of A. baumannii by 100-fold compared to unmodified tissue.

“Bacterial infection is a substantial cause of skin graft rejection and additional health care costs,” says Lynn Allen-Hoffmann, Ph.D., Stratatech’s founder, chief scientific officer and chief executive. “The potent anti-infective capability Stratatech has engineered in our living human skin substitute can be an important tool in improving skin-injury patient outcomes and in reducing the incidence and expense of hospital-acquired infections. We look forward to beginning the clinical evaluations of our antimicrobial skin substitute in the near term.”

The new tissue is being developed through a worldwide exclusive license from the Wisconsin Alumni Research Foundation.

The company’s work on genetically engineered living human skin substitute was funded in part by a Small Business Innovative Research grant from the National Institute of Diabetes and Digestive and Kidney Diseases.