Genetically Engineered Skin Substitute Is Designed to Promote Wound Healing

BUFFALO, N.Y. -- Bioengineers at the University at Buffalo and Shriners Burns Hospital-Boston have created a genetically engineered skin that expresses a protein that promotes wound healing. It is believed to be the only artificial tissue designed to express keratinocyte growth factor, KGF.

Their research, published today (April 1, 2001) in the FASEB Journal of the Federation of American Societies of Experimental Biology, suggests that a skin substitute could be developed that would accelerate the generation of new skin following severe injuries or burns.

The research demonstrates for the first time that a growth factor can bring about significant changes in the three-dimensional organization and function of a skin equivalent in vitro.

Stelios T. Andreadis, Ph.D., assistant professor in the UB Department of Chemical Engineering, director of the UB Bioengineering Laboratory and lead author on the paper, said the researchers have submitted a grant proposal for animal studies aimed at confirming whether the artificial skin would have a therapeutic effect.

The co-authors are Karen E. Hamoen, Martin L. Yarmush and Jeffrey Morgan, all of Massachusetts General Hospital, Harvard Medical School and Shriners Burns Hospital-Boston.

"Our goal was to create genetically modified skin equivalents that secrete keratinocyte growth factor as a means to accelerate wound healing," said Andreadis.

"We also wanted to create a model system to study the effects of this protein on the development and morphogenesis of engineered skin tissues."

Andreadis said the presence of KGF "appears to have profound effects on wound healing, by spurring the proliferation of skin cells."

He added that the genetically modified tissue substitute has a number of advantages that make it a good candidate for a skin substitute.

"What's significant about our substitute is that it contains the basement membrane -- the matrix molecules that the cells of the epidermis like to sit on -- that retains the natural composition and topography of skin," he added.

The genetically engineered skin also has high mechanical stability and is pliable, important advantages over skins made from collagen gels, which, he said, have a consistency similar to that of gelatin and therefore are much more difficult to use.

Most important, Andreadis explained, the engineered tissue has good barrier function, preventing dehydration and protecting against pathogens.

"This is very important for burn patients who have lost a substantial fraction of their total body surface area and who suffer from excessive dehydration and bacterial infections," he said. "Because they are very much like real skin, the engineered cell-based skin equivalents can provide these functions."