Bioengineered tissue offers new hope for wound and burn patients
Products are new, but results look promising
(Editor’s note: This is the first of a two-part series on one of the newest advances in wound healing bioengineered skin. In the March issue of Subacute Care Management, we’ll discuss techniques for application of these new products to patients.)
Bioengineered tissue, a technology that was considered revolutionary only a few years ago, is on the verge of becoming one of the most important breakthroughs in the treatment of burns and chronic and acute dermal lesions.
Considering the fact that millions of people suffer from various types of dermal wounds, the possible clinical and economic impact of products that accelerate healing is apparent. For instance, by many estimates, the direct and societal costs of treating nonhealing pressure sores, venous ulcers, diabetic ulcers, and burns runs into billions of dollars annually in the United States alone. Should bioengineered skin and related products prove to be more effective and predictable than the myriad of wound dressings now on the market, the potential to decrease suffering and costs will be remarkable.
One company’s trial showed that when its bioengineered tissue was used, 100% wound closure was achieved in a median 57 days, compared with 181 days for patients receiving standard care. (For details, see related story, p. 15.)
Conceptually speaking, bioengineered skin (also referred to as skin equivalent or artificial skin) is a straightforward proposition. In one representative model, a three-dimensional matrix fabricated from a bioabsorbable organic material serves as a nursery, so to speak, for living skin cells, explain sources at Smith and Nephew, an international company involved in tissue engineering. This nonliving scaffolding supports the growth and expansion of dermal and/or epidermal cells that have been harvested from a donor.
Nonhuman donors can be used
Depending on the type of skin equivalent being produced, donors can be human or nonhuman. When maintained in the proper environment with the right nutrients, the cells will grow within the framework of the scaffolding.
Cells used to seed the matrix may be cultured in vivo or in vitro, during which time they bond to the scaffold material and eventually begin to perform their intended functions. The scaffolding materials can be natural (e.g., collagen, hyaluronic acid) or synthetic (e.g., polyglycolic acid, polyactic acid). Organs besides skin also have been targeted for tissue engineering, such as cartilage, the liver, and vascular system components.
Once the graft is applied to a patient’s wound or burn, it acts as either a temporary covering (until an autograft or other treatment can be applied) or permanent skin replacement, says George McKinney, PhD, chief operating officer of Integra LifeSciences Corporation in Plainsboro, NJ. Bioengineered grafts can be attached via sutures, staples, or simple compression and need a moist environment to ensure their survival. A moisture-retaining dressing may be used for this purpose.
Bioengineering firms are taking several therapeutic approaches to developing skin equivalents. Epidermal replacements consist of keratinocytes grown alone or in close association with a carrier vehicle, such as a polymeric film or bio-reabsorbable matrix.1 Dermal replacements consist of a structure able to support the infiltration, adherence, proliferation, and production of new fibroblasts. Full-skin substitutes combine components of both epidermal and dermal replacements, McKinney adds. Bioengineered skin can be categorized by the sources of their biological building blocks, as follows:
• Autologous bioengineered tissue, or autografts, are harvested from a donor patient and then are grafted back onto the donor, says Liza Ovington, PhD, president of Ovington and Associates, a wound care consulting company in Fort Lauderdale, FL. One benefit of autografts is that they stand a very small chance of being rejected, and the risks of disease transmittal are small. On the other hand, this type of graft requires time to develop and cannot be used on demand. In addition, graft harvesting is a painful procedure.
• Allogenic grafts, or allografts, originate from a donor source and are grafted onto a different recipient. Allografts bear increased potential for graft rejection and disease transmission, making pre-graft tissue screening for pathogens crucial. Because they do not require the recipient to double as the donor, allografts can be stored indefinitely and then used immediately, explains Gary Gentzkow, MD, executive director of worldwide medical affairs at Advanced Tissue Sciences in La Jolla, CA. A common source for human allografts is neonatal foreskins that are intensely screened for bacterial and viral contamination.
• Xenogenic tissue grafts, or xenografts, are transferred from one species to another. This process has not gained widespread favor among tissue bioengineers with regard to wound repair.
Two tissue-engineering therapies have been tested on a large scale for chronic wounds and are awaiting Food and Drug Administration approval. Both of them contain living cells, says William H. Eaglstein, MD, chairman of the department of dermatology and cutaneous surgery at the University of Miami School of Medicine in Florida. One therapy starts as a mesh of absorbable surgical suture. Live dermal skin cells are taken from a neonatal foreskin and added to the mesh in a chamber of growth media. The tissue that grows from the skin cells is laid down over the ulcer, and the bioengineered tissue begins to heal.
"We have reason to believe it heals by stimulating the host tissue," Eaglstein says. "We think that the engineered skin isn’t really even there after the healing is complete. "
The second therapy is more complex, beginning with connective tissue such as a tendon from a cow. That tissue is transformed into a gel that is combined with dermal skin cells from a neonatal foreskin. After the two have grown together, a layer of epidermal cells is added on top. This provides a two-layered skin with both layers composed of living cells, says Eaglstein.
With both therapies, the skin grafts are applied once a week for several weeks, one on top of another. Eaglstein notes that the second type of bioengineered tissue therapy shortened the healing time of venous ulcers from about 150 days to 50 days. Rejection of these engineered tissues has not been a problem, he adds.
Not all skin replacements contain living skin cells. Instead, they rely on in vivo tissue regeneration. Some consist of the scaffolding component alone; when applied to a wound, they support the expansion and growth of healthy skin at the wound margins.
Reference
1. Parenteau NL, Sabolinski ML, Mulder G, Rovee DT. "Wound Research." In: Krasner D, Kane D. Chronic Wound Care. 2nd ed. Wayne, PA: Health Management Publications; 1997, pp. 389-395.
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