Exploring The Potential Of Bioengineered Alternative Tissues

Pages: 22 - 29
Clinical Editor: Lawrence Karlock, DPM

Bioengineered alternative tissues, or skin substitutes, can lead to success in patients with wounds that have not responded well to other modalities. Accordingly, our expert panelists offer a closer look at where these products fit into the wound healing armamentarium and share pertinent pearls from their clinical experience with these products. Q: What skin substitutes do you utilize in treating lower extremity wounds? A: Paul Kim, DPM, has had success using Apligraf® (Organogenesis) for more superficial chronic wounds. He cautions practitioners that it may take multiple applications of Apligraf to convert a chronic wound to an acute wound. Apligraf works well at stimulating granulation tissue, according to Dr. Kim. He adds that sometimes wounds treated with Apligraf attain complete closure without the need for a split-thickness skin graft (STSG). Dr. Kim finds Integra® (Integra Life Sciences) works well in deeper wounds and decreases the overall wound depth. He uses it to build up the floor of the wound and notes he may follow up by applying Apligraf. As Dr. Kim states, the conjunctive use of negative pressure wound therapy also appears to speed up the wound healing process. Michael Miller, DO, has used Apligraf and Oasis (Healthpoint) in his outpatient practice with “excellent” results. He participated in Oasis trials and found success in using the product to help treat venous and diabetic ulcers. Dr. Miller has also used Dermagraft (Advanced Biohealing) to facilitate healing in difficult wounds. John S. Steinberg, DPM, prefers the term “bioengineered alternative tissues” (BATs) to “skin substitutes,” which he feels can be “very misleading.” He often uses Apligraf and Integra in the OR and the clinic setting. Dr. Steinberg is just starting to have experience with Graft Jacket (Wright Medical). Q: What products do you prefer for a plantar neuropathic diabetic ulcer and why? A: Dr. Steinberg describes this as “a loaded question,” saying the true variable is the depth of the wound and not the anatomic location. He uses Integra for deeper wounds that require regeneration of deep soft tissue layers. Dr. Steinberg uses Apligraf for more superficial wounds in order to facilitate epidermal growth and closure. The key to healing plantar wounds does not depend on the product that one utilizes, according to Dr. Kim. Rather, he says the most important concept is offloading. As Dr. Kim notes, one needs to accommodate or surgically remove/reconstruct the offending bony prominence. “Without dealing with the underlying focal pressure, all BAT products will fail eventually,” claims Dr. Kim. When it comes to plantar neuropathic diabetic ulcers, Dr. Miller cites Regranex, Promogran and Promogran Prisma (Johnson and Johnson) as effective. He applies Apligraf to non-infected, mostly granular wounds. Dr. Miller notes the product forms epithelial tissue quickly and fills the wound depth. He says one can apply GraftJacket to deeper, necrotic wounds with bone or tendon involvement. The product seals the wound from the outside environment and also incorporates into the tendon, decreasing the potential for tendon loss, according to Dr. Miller. Dr. Miller also uses PriMatrix (TEI Biosciences), a new acellular collagen dermal tissue matrix derived from fetal bovine skin. As he explains, the body can remodel the matrix into a functional tissue and the product becomes easily vascularized. “My goal is to promote healing through improved patient compliance by making the treatments as simple and involving as little patient manipulation as possible,” says Dr. Miller. Q: Do you ever utilize split-thickness or full-thickness skin grafts on the plantar foot? A: To cover defects on weightbearing areas, one can use a well-designed rotational or transpositional flap, according to Dr. Kim. He recommends designing the flap in such a fashion so it is derived from a non-weightbearing area. Dr. Kim says one can use a STSG to graft the area vacated by the flap. By using such a technique, Dr. Kim says he has not had to use a full-thickness graft. Dr. Steinberg uses both types of grafts. He says clinicians may now use bioengineered alternative tissues and VAC therapy (KCI) to regenerate the plantar soft tissue layers first and then apply a glabrous STSG. “We perform drastically fewer free flaps using this approach,” notes Dr. Steinberg. On the other hand, Dr. Miller says with the availability of “so many excellent skin substitutes out there,” he is reluctant to create a donor wound to heal a patient’s primary wound. Q: How would you compare Graft Jacket to Apligraf and Oasis? A: Oasis, a porcine intestinal submucosa, offers an acellular matrix scaffold that provides a foundation for wound healing, according to Dr. Miller. He notes the tissues replace the porcine cells with human cells. Oasis, which Dr. Kim calls “readily available and accessible,” has worked better for him for superficial venous ulcers. Dr. Steinberg mostly uses the biologic dressing for superficial wounds or as a follow-up to Apligraf or a STSG. As Dr. Miller describes it, Apligraf is a living bilayer skin substitute that provides a dermal and epidermal layer with 48 growth factors. The product is layered on a bovine collagen scaffold and, as he says, “provides all the tissues needed to heal a wound and the growth factors to jumpstart the wound.” Dr. Kim says Apligraf is “more versatile” and one can use it in both deep and superficial diabetic and venous wounds. However, he notes Apligraf is more expensive than Oasis and needs more preparation. Apligraf has been “of great benefit” in Dr. Steinberg’s practice and he notes it is the only living bioengineered tissue for diabetic foot ulcerations. Dr. Steinberg describes Graft Jacket as a processed allograft that serves as a biologic dressing with a number of wound benefits. “They are each very unique products and can offer significant benefit when applied to the right wound at the right time,” notes Dr. Steinberg. Q: When do you utilize these advanced skin substitutes, earlier or later, in the treatment of a wound? A: Early utilization of these advanced wound products is important, according to Dr. Steinberg. “The mentality of waiting for a wound to become chronic and fail a lengthy care regimen is outdated,” he continues. “The sooner you intervene with advanced healing modalities, the better the wound bed will be prepared to receive them.” He says it is not very difficult to identify patients who will have problems with wound healing. Measuring wounds weekly “will tell you volumes,” emphasizes Dr. Steinberg. Dr. Kim reiterates that BAT products are not “skin substitutes” as they are not meant to replace skin. He adds that BATs convert chronic wounds to acute wounds or provide a scaffold for tissue to penetrate. Dr. Kim says one can use BATs early in wound care but he normally waits until seeing evidence that the wound has become chronic. To measure this, he uses Sheehan’s yardstick, saying one should expect wounds to heal at a rate of about 10 to 15 percent per week or decrease by 50 percent in one month.1 If the healing rate is below the aforementioned benchmark, Dr. Kim uses BAT products to “kick-start” the wound. If Dr. Kim is unhappy with the wound’s healing progression, he will change the BAT product to another. Dr. Kim lets smaller wounds heal by secondary intention. When it comes to a wound with a large surface area and a nice granular bed, Dr. Kim says he will apply a STSG. Initially, Dr. Miller tends to use less expensive products. He says offloading is key and also cites the basic tenets of wound care (i.e. frequent debridement, keeping the wound moist, etc.) and good glycemic control. If a patient does not respond or plateaus, Dr. Miller reassesses the patient and tends “to go to a more advanced product.” Q: Do you have any pearls when it comes to post-op dressings with these products? A: Dr. Miller prefers using Versatile 1 (Blue Sky Medical) due to its lower pressures and ease of use. He adds that several of his colleagues have had satisfactory results with it. For him, the keys are constant negative pressure to “secure” the graft down and enhance healing. He feels this results in faster and better “take,” and ultimately quicker recovery and ambulation for the patient. As far as BAT products go, Dr. Kim is mainly concerned with their stability in the wound bed following application. He recommends tacking the BAT down with staples or stitches around the edge of the wound. Dr. Kim also says one can find success by using non-adherent dressings like Mepitel® or Adaptic® over the bioengineered alternative tissues. He advises using a porous dressing since it will permit the exudates to drain from the wound. When it comes to an outer dressing, if one is not using negative pressure wound therapy, Dr. Kim suggests using any combination of a dressing sponge with Kerlix® or Kling®. For Dr. Steinberg, the choice is straightforward. One should use a nonadherent dressing for the first layer, an antimicrobial dressing for the second layer and a dressing that retains moisture for the third layer. He says deeper wounds often necessitate VAC therapy to manage the drainage appropriately and to keep the graft material adherent to the wound base. Dr. Kim is an Associate of the American College of Foot and Ankle Surgeons. He is an Assistant Professor at Midwestern University College of Health Sciences. Dr. Miller is certified in chronic wound management and board certified in general surgery. He is the Medical Director of four wound healing centers in Indiana. Dr. Steinberg is a Fellow of the American College of Foot and Ankle Surgeons. He is an Assistant Professor in the Department of Plastic Surgery at the Georgetown University School of Medicine in Washington, D.C. Dr. Karlock (pictured) is a Fellow of the American College of Foot and Ankle Surgeons, and practices in Austintown, Ohio. He is a member of the Editorial Advisory Board for WOUNDS, a Compendium of Clinical Research and Practice.



References 1. Sheehan P, Jones P, Caselli A, Giurini JM, Veves A. Percent change in wound area of diabetic foot ulcers over a 4-week period is a robst predictor of complete healing in a 12-week prospective trial. Diabetes Care 2003 Jun;26(6):1879-1882.


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