Cultured skin substitutes speed recovery from massive burn injuries
By Glenn D. Warden, M.D., and Steven Boyce, Ph.D.
July 10, 2001
Pediatric burn injuries are one of the greatest hazards of childhood, injuring more than 100,000 children each year. Many of these injuries are severe enough to require multiple surgeries to replace and heal the damaged skin. Among the many requirements for recovery from such a massive injury is the permanent replacement of burned skin to restore the protective barrier against infections and other complications. Cultured skin substitutes provide alternatives for the patient and the clinician for faster closure and healing of massive burn wounds.
Since 1990, the tissue engineering laboratory at the Cincinnati Shriners burn hospital has achieved remarkable success in closure of burn wounds using cultured skin grafts. This approach provides an experimental alternative to skin grafting in cases where enough unburned skin is not available for use as a donor site. The cultured skin grafts are made from the patient's skin cells, in combination with a medical fabric that dissolves after grafting to the wound.
From a biopsy of skin as small as four square inches, cells are isolated from the outer skin (epidermis) and from the inner skin (dermis). The cells are then grown in a special nutrient solution that stimulates them to divide exponentially (2, 4, 8, 16, 32, 64, etc.), and they can then be stored in liquid nitrogen for many years if needed. From this small skin area, the lab team can grow large populations of cells that are combined with a fabric made from a natural protein called collagen.
After combining the skin cells with the fabric, the outer surface is exposed to the air which stimulates development of the epidermal barrier, or the protective surface of the skin. Cultured skin grafts are then taken to the operating room where the surgeon applies them to the patient's wounds and puts a traditional burn dressing over the area. The wounds are healed usually within one to two weeks after grafting, and the patient is able to begin the rehabilitation phase of his recovery.
Cultured skin grafts are most valuable in patients who have received second- or third-degree burns over more than 50 percent total body surface area, which limits availability of donor skin for conventional skin grafting. In catastrophic burns of more than 80 percent of the body surface, availability of donor skin is very limited, as is the number of times that the same donor site can be used for regular skin grafts.
In addition, the maximum expansion of donor skin by conventional grafting is about four times the area of the donor site. By comparison, cultured skin can be grown to more than 100 times the area of the biopsy. In theory, this means that the entire body could be covered with cultured skin starting with just about one percent of the body surface, or about the size of the palm of the hand. Enough cultured skin can be grown to cover the catastrophic burns in about two months from the time of injury.
Shriners Hospitals and the University of Cincinnati are working closely with the U.S. Food and Drug Administration (FDA) to gain approval for this method as a valid alternative to conventional skin grafts. We are collecting data to submit to the FDA for evaluation. After our data are reviewed, the next step is to reproduce these therapeutic benefits at other hospitals. Toward this goal, multi-center studies are being planned. Successful completion of these studies is required before this advanced treatment method can be introduced as a routine therapy.
This year alone more than 15 patients have benefited from the cultured skin grafting method at the Cincinnati Shriners Hospital. These cases demonstrate two important accomplishments for the research team. First, because less donor skin is required, the number of surgical procedures to harvest donor skin is reduced, and there is less scarring of donor sites. Second, because harvesting and healing of donor sites are reduced, healing of donor sites is faster, and the time required for final wound closure is also reduced. Wound closure is a major milestone in recovery from massive burns because it reduces the risk of other complications. In addition, the functional and cosmetic outcome after treatment with cultured skin substitutes is no different than treatment with conventional skin grafts.
To evaluate the quality of healed skin after treatment with cultured skin substitutes, a central focus has been placed on the clinical outcome - in terms of function and cosmetic properties of the healed skin. The tissue engineering lab here at the Cincinnati Shriners burn hospital uses instruments to measure the parameters of these outcomes on a numerical scale. The lab has adapted instruments developed for dermatology that can evaluate the hydration, softness, color, shape and blood flow of the healed skin. These instruments provide benchmark standards for researchers and clinicians to compare individual skin properties by clinical examination. Establishing these standards for skin composition and performance of engineered tissues, including cultured skin, has been undertaken by the American Society for Testing and Materials, the FDA and Shriners Hospitals.
Another future goal for our tissue engineering lab involves the restoration of normal skin color after grafting of wounds with cultured skin. Normal skin color has been documented in preclinical studies with cultured skin, and it is expected that skin color matching in clinical treatment will soon become a reality.
Use of cultured skin substitutes for wound closure has reduced the amount of donor skin required by more than 10 times compared with conventional skin grafts. Effective wound closure with these skin substitutes has reduced the number of surgeries to harvest donor skin and decreased the time of recovery of severely burn-injured children.
The medical advantages of the skin substitutes, together with comprehensive care of the burn team, have contributed to the recovery of patients with greater than 90 percent burns. For these patients, additional cultured skin grafts can be made for reconstructive surgery without additional donor sites. This combination of advanced technology with high quality outcome is expected to allow use of cultured skin for treatment of burn scars and other plastic surgery procedures in the near future. Introduction of these advances is expected to result in faster recovery, fewer complications and improved outcome in the treatment of catastrophic burn injuries.
July 10, 2001
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