There have been many technological advances in wound care over the past decade, ranging from research into the wound healing model to the role of growth factors and the use of living skin constructs in clinical practice. With this in mind, our expert panelists take a closer look at Apligraf and their experiences in using this product. Q: Do you use Apligraf much in your practice? If so, when do you use it in the course of treatment? A: Both Robert Snyder, DPM, and Sheldon Ross, DPM, use Apligraf frequently in their practices. David Armstrong, DPM, says he uses Apligraf if he does not see predictable healing following three to four weeks of conservative therapy, which consists of aggressive debridement and offloading. Dr. Ross concurs, noting that he usually uses the product to treat diabetic or venous stasis ulcerations that do not respond to conventional wound care within four to six weeks. He also uses Apligraf on several patients who have large wounds, which require more than one graft per site. “A construct such as Apligraf can also act as a ‘stimulatory packet,’ which may form a matrix that was previously lacking. It is, in essence, a ‘bag of growth factors,’” explains Dr. Snyder. Although the FDA has approved Apligraf for treating diabetic ulcerations and venous ulcers, Dr. Snyder believes the modality can also help treat problems including burns, status post-Mohs cancer surgery and pressure ulcers. Q: Some doctors do not feel comfortable working with Apligraf because it is cumbersome to handle and tears easily. What has been your experience and what techniques do you use? A: Although he doesn’t think working with Apligraf is difficult, Dr. Snyder says you may need practice to master the technique and offers the following advice. First, drizzle saline over the Apligraf before removing it from the container. Then grasp the graft with two atraumatic forceps at 10 o’clock and 2 o’clock. Gently lift the Apligraf from the container and place it epidermis down on the inside of the top cover. If you have a mesher, place the graft down on a carrier of 1.5:1 in the same fashion. Pie-crust with a #11 blade or mesh, if appropriate. Bring the top cover (or carrier) to the wound. Gently tease the graft off the cover and place it on the wound. If you place the graft on the cover or carrier with the epidermis down, you can easily place Apligraf on the wound, dermis side down, without repositioning the graft. There is almost no graft manipulation or excessive handling, according to Dr. Snyder. Dr. Armstrong recommends applying the product manually and then using cotton-tipped applicators to help spread the tissue over the wound site. He tends “to allow for a great deal of overlap of the graft over the margins of the wound.” Dr. Ross says he has had no problems with graft tearing and does not think working with Apligraf is cumbersome. “The worst problem I have experienced is the rolling of the graft edges, but if you maintain proper epidermal-dermal orientation, you won’t have a problem applying the graft,” points out Dr. Ross. “I work in a close sterile environment, transferring the graft from the transfer media container directly to a mesh plate.” Dr. Ross says he carefully teases the graft edge from the container with the blunt side of a scalpel handle, grasps it on two ends using sterile forceps in each hand and transfers it epidermal side down. If necessary, he trims the graft and then either meshes or incises it using a #11 blade. Then he brings the mesh plate directly to the wound site with the dermal side up and inverted and places the graft directly into the wound. Q: In your experience, does Apligraf actually “take” like an autograft? What would you expect to see on the first post-operative visit? A: In his experience, Dr. Ross says there have been many cases in which Apligraf took like an autograft. However, Dr. Armstrong disagrees, saying he believes many people made mistakes initially because of their expectations in terms of what to look for. “What was once considered by some to be ‘slough’ on the wound one to two weeks post-grafting is now known to be metabolically active graft,” explains Dr. Armstrong. “One should not disturb this until it dissipates. Other bioengineered products, such as Dermagraft, behave differently in the wound. Therefore, there is definitely an observational as well as a mild technical learning curve to overcome in order for these modalities to reach their full therapeutic potential.” Dr. Ross always tells his patients to expect their grafts either to take like regular skin grafts or act as wound dressings to promote better healing. “I like to check the graft site after four days, so I almost always see a normal appearing graft site, that is one with normal appearing skin as a graft,” offers Dr. Ross. For Dr. Snyder, the topic of Apligraf taking like an autograft is “somewhat controversial.” He says Apligraf likely incorporates into the wound and does not take in the traditional sense, leading to a different clinical appearance, especially on the first few dressing changes, the first of which typically is in five to seven days. “Therefore, the wound may have a slight malodor and occasionally the graft appears to be sloughing off,” explains Dr. Snyder. “The surrounding tissue may be somewhat macerated. This clinical appearance is usually no cause for alarm and, in most cases, does not represent infection.” If you see no signs of clinical infections, Dr. Snyder warns to resist the temptation of debriding away the graft, culturing the wound which remains and starting the patient on antibiotics, pending results of the cultures. Instead, he recommends you see the patient more frequently and carefully monitor him or her. He says in most cases, the graft will start to solidify and incorporate itself into the wound bed. Q: What method would you typically use to adhere the graft to the wound bed? What dressing would you use for subsequent dressing changes? A: All three DPMs suggest using mepitel or another product to stabilize the wound. Dr. Armstrong says typically, he either staples the graft to the bed or simply lays it on without attachment. He says he has found some benefit in using a silicone-based non-adherent dressing, like mepitel, over the wound. Dr. Armstrong also has found great utility in pre-treating his patients for one or two weeks with a dressing which contains silver, such as Acticoat (Smith and Nephew). “Silver, which has significant broad-spectrum antimicrobial properties, can substantially reduce the bacterial bioburden in the wound and thus improve results,” says Dr. Armstrong. Dr. Snyder suggests using mepitel or Xeroform gauze to stabilize the graft against the wound bed and notes there are other available alternatives, including sutures, staples and steri-strips. First, Dr. Snyder says you should apply mepitel or Xeroform gauze carefully over the graft and then apply a layer of Lyofoam gauze or comparable hydrocellular dressing material. If you expect a fair amount of drainage, cut additional strips of this material and place them over the original hydrocellular dressing. Apply gauze, a gauze roll and Coban. If you are treating a patient with venous ulcer disease, Dr. Snyder says the compression should go from behind the toes to below the knee. He recommends keeping the dressing in place for five to seven days and repeating it every time you change the dressing. Dr. Ross says he likes using the “old-fashioned” method of suturing his grafts in place with simple nylon sutures. He puts a piece of mepitel over the wound and places sterile, saline-soaked cotton balls over the mepitel in the wound to ensure good adherence between the graft and wound bed. Dr. Ross then covers it with four-by-fours and secures it with kling. Then he utilizes a compression bandage, anything from Profore to simple tubgrip, depending on the patient’s vascular status. Dr. Ross says subsequent dressings will consist of non-adherent dressing, often Vasoline-impregnated gauze and kling. Q: Has Apligraf been of significant value to your patients? How often do you have to reapply the grafts to accomplish healing? A: Dr. Snyder and Dr. Ross say patients have found Apligraf beneficial. Dr. Snyder says he reapplies the product for “extremely recalcitrant wounds,” but will wait six weeks before doing it. Dr. Ross rarely has had to reapply a graft. Usually, Dr. Armstrong uses one or two applications of Apligraf. “Many wounds that were previously resistant to healing or required autograft can now be treated safely and expeditiously in an office setting with consistent results,” emphasizes Dr. Snyder. Dr. Snyder (shown below) is a Diplomate of the American Board of Podiatric Surgery and the American Academy of Wound Management. Dr. Armstrong is the Director of Research and Education within the Department of Surgery, Podiatry Section at the Southern Arizona Veterans Affairs Medical Center. Dr. Ross is a Diplomate of the American Academy of Wound Management.
References 1. Snyder RJ. Graftskin (Apligraf) and regranex gel: an overview. Podiatry Management. November/December 2001: 39-50. 2. Falanga V, et. al. Prognostic factors for healing venous and diabetic ulcers. Wounds 2000; 12 (5 supplement): 42A-46A.