Treating nonhealing wounds with advanced therapies requires knowing exactly what you're treating. For example, when considering engineered tissue products for wound healing, "As always, we want to treat the cause of the wound, prepare the wound bed and treat patient-centered concerns," says Severin Laeuchli, M.D., a dermatologist with the University of Zurich's department of dermatology.
Regarding the wound bed, he says options to assist epithelialization include skin grafts and engineered tissue products. In the latter area, "We can culture fibroblasts, keratinocytes and dermal matrix. All these components play important roles in the wound-healing process. They aid in the migration and proliferation of cells, in the production of extracellular matrix and growth factors and in angiogenesis and protease release. They can also build a scaffold to support new tissue."
Providing scaffolding is a function of most acellular wound-repair products such as Integra (bovine collagen, Integra LifeSciences), he says.
Cellular wound-repair products include epidermal equivalents such as EpiDex (human keratinocytes, Modex Therapeutics) and bilayered skin equivalents such as Apligraf (bovine collagen/human fibroblasts, keratinocytes; Organogenesis).
EpiDex is cultured from keratinocytes from patients' autologous outer hair-root sheath cells because "their proliferative potential does not depend on age of the donor," Dr. Laeuchli says. "The product is delivered on silicone sheets, which are placed on the wound in nonoverlapping fashion. Then the wound is dressed with an absorbent dressing. The lower level of dressing is left on the wound for at least a week."
Many cases require a second layer of cultured skin equivalent later in the process, Dr. Laeuchli says.
In an observational study of the first 68 patients that Dr. Laeuchli and his colleagues treated with EpiDex, "Three-quarters of their ulcers were healed after the nine-month observation period. Only 12 percent showed no response (Ortega-Zilic N, Hunziker T, Läuchli S, et al. Dermatology. 2010;221(4):365-372. Epub 2010 Nov 11).
"Another interesting observation was that 78 percent of patients had complete remission of pain," Dr. Laeuchli says. "We also calculated that the treatment was cost-effective compared to split-thickness skin grafts because in most cases, there's no need for a hospital stay."
One study patient, a woman with pyoderma gangrenosum (PG) who was on immunosuppressive medication and developed a pretibial ulcer, underwent two applications of EpiDex and was completely healed in about three months.
"This is not a typical indication for a tissue engineered product, but PG is very difficult to treat because one must avoid mechanical stimulation of the ulcer," he says.
Apligraf consists of dermal and epidermal layers cultured from human neonatal foreskin keratinocytes and fibroblasts in a matrix of bovine and human collagen, Dr. Laeuchli says. It's approved by the Food and Drug Administration for venous leg ulcers and diabetic foot ulcers.
"How this product works is not entirely clear," Dr. Laeuchli says. Clinicians do know, however, that it delivers young fibroblasts and keratinocytes to the wound, aids in the production of cytokines and probably growth factors and helps to recruit other cell types. "It does not act as a graft; it modulates wound-healing," he says.
Dr. Laeuchli says that in one patient he treated, a 79-year-old female with a 40-year history of large venous ulcers, five applications of the product between June and November 2010 had nearly healed the ulcer.
For a 92-year-old patient with a 62-year history of painful post-thrombotic ulcers, he says, applying Apligraf immediately improved pain scores. He also has used the product successfully to treat a 29-year-old female patient who suffered from livedo vasculopathy that resulted in foot and ankle ulcers.
"Her main problem was pain, which was not controlled with standard analgesics. We applied this bilayered product on these small ulcers, and after four weeks, the ulcers were almost healed, and the pain drastically reduced," Dr. Laeuchli says.