There is new hope for patients needing skin grafts, as new and improved methods of creating artificial skin may appear in the near future.
In a recent study, Yale researchers have begun to explore alternative artificial skin grafts with improved longevity and reliability, important for patients with compromised blood circulation, diabetics and the elderly.
Jeffrey Schechner, M.D., assistant professor of dermatology at the Yale School of Medicine, created skin grafts using endothelial cells secured from discarded human umbilical cords. Endothelial cells line blood vessels and promote the growth of blood vessels, called vascularization, in the grafts.
Artificial skin grafts have been available for many years to aid healing of burns, persistent ulcers and trauma wounds. The only reliable method of skin grafting has been a graft from another part of the patient’s own body. But for severely injured patients this is not always possible and grafts are derived by artificial means. This method, however, fails to provide an adequate blood supply to deliver oxygen and nutrients to the skin.
“Artificial skin has… not [functioned like an organ] or grafted into the patient,” Schechner said. “They are considered ‘biological dressings.'”
Schechner seeded endothelial cells engineered to over-express Bcl-2, a gene that enhances blood vessels’ growth, into skin stripped of its cells and left only with structural elements. These grafts were successfully transplanted onto mice.
“In addition to using normal endothelial cells, we genetically modified them for better performance … by over-expressing a gene which enhanced the maturation of blood vessels,” Schechner said. “The modification, at least in this study, greatly improves the performance of the blood vessels.”
David Enis, M.D., a Ph.D. student currently participating in another Yale study using endothelial cells, said the technology’s many uses may lead to the development of more complex artificial organs.
“Theoretically this is a technology that could be applied to a variety of synthetic organs,” Enis said. “[Schechner is] using skin, well-suited to making skin grafts, but you could easily put in other cell types to mimic other types of tissue — you could… make a vascularized pancreatic tissue that might be useful in the treatment of diabetes.”
A researcher in Schechner’s study, Jordan Pober, M.D., professor of immunology, pathology and dermatology at the Yale School of Medicine said biological and commercial issues may slow the availability of the new skin to patients. Recipients of skin transplants, like those of any organ transplant, run the risk of immunological rejection of the new organ.
“I think the issue there comes down to … are we going to cause an immunologic response and will we be able to treat that?” Pober said. “If we don’t, [the skin] could, in theory, be ready for clinical trials in very short order … if it does create an immunologic reaction … optimistically in a year or two we could come up with an approach to treat that problem.”
However, Pober said the disappointing economic performance of existing artificial skin could hamper the practical application of this new skin, as companies may be wary of investing.
“The barrier to the science might be moderate, but the barrier to commercializing it and making it available might be never [be met],” Pober said. “It depends on a marketing decision.”
The team received a Roche Organ Transplantation Research Foundation grant, which supports cutting-edge organ transplantation research worldwide. The other researchers included Saara K. Crane, Feiya Wang, Anya M. Szeglin, George Tellides, Marc I. Lorber and Alfred L.M. Bothwell.