Wound healing is complex, and it is dynamic. Exactly how to foster the ideal healing environment has long vexed surgeons across multiple disciplines.
Yes, treatments, which at one time involved amputation, have evolved, but they are still far from perfect. Compression therapy heals only about 70% of ulcers after 6 months. Skin graft surgeries, while less invasive than amputations, confer risk of poor healing at the donor site as well as the host site.
Regenerative medicine approaches wound healing in a totally new way. Treatments including spray-on, cell-based skin substitutes are allowing wounds the chance to heal from the inside out as opposed to the outside in. Slowly, but surely, these therapies are changing the playing field and reshaping how doctors address intractable wounds.
Geoffrey C. Gurtner, MD, a professor and associate chairman of surgery and a professor of materials science and engineering at Stanford University School of Medicine in Stanford, Calif, has watched the field take shape.
“When I trained, we performed major surgery for these slow-healing wounds such as amputations or free flaps,” Gurtner tells Plastic Surgery Practice. “Over the past 10 to 15 years, a variety of technologies have improved care, and there are even more on the horizon.”
The first major development in wound healing was negative-pressure wound therapy, and this has been helpful in avoiding major free flap surgery. “We have progressed to almost universal use of negative pressure in a variety of disciplines,” he says.
Then came the first-generation skin substitutes such as Dermagraft and Apligraf. “These have shown efficacy in randomized control trials, and going forward, there will be new and improved versions that will change how we heal wounds,” he says.
Gurtner likens where we are right now in wound care to where infection control was in the 1930s when Sulfa antibiotics were discovered. “We have a product that works a little bit,” he says of the first-generation skin substitutes. “Over the next 20 to 30 years, we will have something that will work robustly,” he predicts. “We are waiting for our penicillin.”
WOUND, HEAL THYSELF
The skin substitutes show that cell-based therapy works. “Now it is a question of what is the best cell-based therapy for wound healing,” he says. “We don’t know the answer yet, but we will.”
Researchers are now tinkering with different types of cells. At first, they were hot on fibroblast cells from the foreskin of neonates, but these cells tend to disappear. They can, however, deliver growth factors and cytokines to the site of the injury.
The challenge is finding the right cell type and placing it in the right environment and in the right patient, he says. “Regenerative medicine is opening our eyes to which are the right cells for any part of the body,” he says. Different wounds require different cells to heal. “We don’t need the same cells to form bone, form skin, and/or create volume.”
Gurtner’s lab is focused on the environment that leads to scarless healing, and this starts with answering some very basic questions. “Why is it that we could heal without scars at one point in our development but have lost that potential?”
Another challenge is optimizing the delivery system. “Spraying is one way, but it’s not a one-size-fits-all solution,” he says.
To that end, a recent study published in The Lancet highlighted an experimental “spray-on skin” which puts a coating of donated skin cells and blood-clotting proteins over venous leg ulcers. When combined with compression bandaging, the new product resulted in faster healing and greater likelihood of wound closure than compression bandaging alone. Healthpoint Biotherapeutics, Fort Worth, Texas, is developing the product.
“We are moving toward placing cells in the wound and, whether growth factors or other cell products mediate the process, inviting some communication to take place with the wounded tissue,” says Herbert B. Slade, MD. He is a pediatrician at the University of North Texas Health Science Center in Fort Worth and the chief medical officer at Healthpoint Biotherapeutics. “The belief is that the cells have a modulating effect on the wound while they persist, which could include the generation of signals calling stem cells to that location.”
Some labs are using keratinocytes from hair follicles to create discs that can be placed over wounds to stimulate healing, but processing takes up to 5 weeks.”This takes too long, and many patients have already begun healing by the time the disc is ready,” he says. Adipose-derived stem cells can also be procured and processed in a more timely fashion, and may help treat many types of wounds in the future.
When Gurtner gleans his crystal ball, he sees a wide range of wound-healing technologies available on and off the shelf and used in inpatient and outpatient settings. “I think we will have a portfolio of products much as we do in mature areas of medicine that includes cells and delivery devices that lead to accelerated healing in burn patients, diabetes patients, and patients with catastrophic injuries.”
Denise Mann is the editor of Plastic Surgery Practice. She can be reached at [email protected]