Application of new skin equivalents is a straightforward proposition
Application of new skin equivalents is a straightforward proposition
Here’s one practitioner’s step-by-step guide
(Editor’s note: A few years ago, bioengineered skin equivalents were considered in the realm of science fiction. But last month, in the first of a two-part series, we highlighted the rapid growth of this new treatment methodology. In this issue, we describe how one such product is administered.)When the patient presented to Morton Altman, DPM, in Palm City, FL, the outlook wasn’t good. The man had a venous leg ulcer on the right medial malleolus that had been present on and off for 30 years. Skin grafting had been unsuccessful, and the wound periodically broke down. The man’s wife, a nurse, rendered consistent care, and the patient was reportedly conscientious in caring for his wound, which measured approximately 7 cm x 5 cm.
As an alternative to failed curative techniques, Altman applied Apligraf, a skin equivalent manufactured by Organogenesis in Canton, MA, to the wound and re-examined it after four days. He was unsure of the results, so he recovered it and checked again three weeks later. A very thin membrane of skin appeared to have formed over the wound. At four weeks, a dried scab ringed the wound, which had decreased in size. The wound’s edges had developed a black eschar, which Altman clipped off. At about six weeks, the last of the scab came off, revealing healthy skin.
Altman’s clinical trial experience with Apligraf, described as a full-thickness allographic skin substitute that includes both dermal and epidermal components, includes two trials: one involving patients with venous leg ulcers, and the other for patients with diabetic foot ulcers.
Apligraf is approved for use in Canada and Australia, but not yet in the United States. The federal Food and Drug Administration is currently reviewing the product’s premarket approval application for the treatment of venous ulcers. The company reports that Apligraf has been used on more than 500 patients. (For details of other products and their statuses, see chart, p. 14.)
In a hypothetical case, here is the application process Altman follows:
A patient presents with a venous leg ulcer, secondary to varicose veins, located above the ankle joint malleolus. The patient is likely to have had a history of varicose vein problems and probably has worn support stockings. Wound breakdown might have occurred as a result of a bumped ankle.
Altman first conducts a thorough history and physical exam, and appropriate testing to determine with certainty that venous disease is the underlying cause of the wound. Venous ulcers typically appear relatively shallow and clean, though they may ooze quite a bit of fluid. Infections are not as common as with other types of wounds, such as diabetic ulcers. If venous disease is confirmed, but the wound has been present for a month or less, Altman says he would probably opt for more conservative management, such as compression. If the wound is older, he follows this protocol:
• Cleaning.
Clean the wound with saline-moistened gauze and cover it with some type of non-adherent dressing that will not damage the wound upon removal. Apply compression with an Ace wrap or an Unna boot.
• Waiting.
Wait three to five days to see if the wound begins healing on its own. If improvement is seen, Altman continues conservative treatment. If the wound appears the same or worse, he considers using Apligraf. "You want to heal the wound as fast as possible," he says. "The longer the wound is present, the greater the chance for morbidity, the more difficult it is to heal, and the higher the cost. I would now proceed aggressively," says Altman. "You will certainly hear varying opinions on this, and some would say to continue conservative treatment for several months before using Apligraf. But I would go with Apligraf if there isn’t 20% to 30% wound closure within the first week after I’ve seen the patient."
• Preparation.
Prepare the skin replacement for application. The product is shipped by overnight delivery and has a stated shelf life of five days at room temperature or a little warmer. It is stored in a petri dish containing a growth medium. Altman stores Apligraf in an incubator until needed. Once teased out of the growth medium, the Apligraf membrane is ready for placement on the wound. Altman first trims the membrane to 10% to 20% larger than the wound. The side of the membrane that is in direct contact with the growth medium is the dermal layer, which is placed against the patient’s skin.
• Application.
Apply the membrane to the wound. Once the membrane is in place, Altman trims it finely with iris scissors so its edge just covers the wound margins. Sometimes the membrane needs to be fenestrated, or cut with small slits. "Venous ulcers tend to exude a lot of fluid, which needs a route to escape through or around the Apligraf," Altman explains. "If those escape routes aren’t available, the membrane could float right off the wound."
• Covering.
Cover the wound with non-adherent dressing (Altman finds Tegapore or Telfa suitable), and apply a compressive wrap to hold the membrane against the wound. "You don’t have to suture, because the Apligraf is in direct contact with the wound," he notes.
Use gauze to push membrane into deep wounds
In the case of deep wounds, which are common in diabetic foot ulcers, greater care needs to be taken to ensure that the Apligraf membrane is in direct contact with the wound bed, he says. In such cases, Altman bunches up some gauze and gently pushes the Apligraf/dressing assembly down into the wound. "There has to be intimate contact between the membrane and the wound, or the skin replacement won’t have a chance to take," he explains.Diabetic foot ulcers present additional challenges. The wounds are usually on the bottom of the foot in a weight-bearing location. Even when patients have crutches, they often put weight on the wound, decreasing the likelihood that any treatment will be successful, including bioengineered skin equivalents.
After a couple of days, Altman changes the dressing and observes the progress of the wound. A couple of events may have taken place:
— The Apligraf may have begun to biodegrade, in which case the wound may appear pus-filled, cheesy, and thickened. That does not indicate an infection, however; just the degradation of the original membrane. "It shows that the replacement is still active and still able to emit cytokines," he says.
— Another possibility is that the Apligraf adheres to the wound, and the first stages of healing become apparent. The rate of healing varies tremendously by patient. "The wound may look a little shallow because there’s nothing to fill in underneath, but it still looks like it’s healing," adds Altman.
— A third possibility is that the membrane doesn’t adhere to the wound, and either comes off when the dressing is removed or has floated completely off the skin.
If you’re not certain about what has transpired and the wound looks beefy red with signs of granulation tissue, Altman recommends redressing the wound and checking it again in three weeks to a month. If the membrane has not adhered or if the wound has not shrunk by about 50% or more, Altman usually applies another layer of Apligraf.
Interestingly, Altman has had the best results when Apligraf is applied to large venous ulcers that have persisted for a year or more. "They responded far better than ulcers of short duration or smaller ulcers," he says. That’s why he initially chooses conservative treatment for short-duration wounds before turning to skin replacement.
He noted that some patients respond very quickly to Apligraf (i.e., two to three days), while others don’t exhibit results for weeks. Failures also occur. A high bacterial load in the wound decreases the chance of success.
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