New Tissue Helps Patients Heal Themselves

Originally Published MDDI June 2002

MEDICAL DESIGN EXCELLENCE AWARDS 2002

Dermagraft

Submitted by IDEO (Palo Alto, Calif.); manufactured by Advanced Tissue Sciences Inc. (La Jolla, Calif.)

In 1998, Advanced Tissue Sciences Inc. (ATS) and IDEO won recognition in the first annual MDEA competition for their development of Dermagraft-TC, the first tissue-engineering product approved by FDA. Four years later, they've won MDEA gold for another first: creating a cryogenically preserved, metabolically active human tissue product.

While both are dermal skin products, Dermagraft-TC, now called TransCyte, is a temporary skin covering comprising nonviable cells that is used to heal burns. Its new sister product, Dermagraft, promotes the growth of new skin over hard-to-heal diabetic foot ulcers.

Key to this year's winning entry were advances in the manufacturing process used to create Dermagraft tissues. Dermagraft-TC was grown in 4 x 6-in. sheets using a labor-intensive process that required manual seeding of the cells, space-consuming rotation of the growth containers, and manual injection of the growth culture medium.

The process of growing the new Dermagraft product has been streamlined considerably by using a specially designed bioreactor system with stackable growth manifolds. Each growth manifold includes eight 2 x 3-in. pouches containing matrices that can be automatically seeded, rotated, and fed with growth medium. When growth is complete, the manifold is placed into specially designed equipment that automatically seals and separates each pouch for final packaging. The automated process preserves the aseptic manufacturing environment, minimizes manual operations, and results in a product packaged in the size preferred by physicians.

Currently, most skin ulcers are treated with antibiotics, saline washes, wound debridement, and bandaging, but the wounds heal slowly, if at all. In clinical trials and initial market use, when Dermagraft is applied once a week for up to eight weeks, up to 70% of patients achieve complete healing. "Wounds that have been open for up to two years that didn't respond to other treatments closed in a few weeks when Dermagraft was applied," says Dawn Applegate, ATS director of technology development.

Much of the reason for that success is the fact that the product's live cells, which are embedded in a tissue matrix secreted by the cells, serve as a template for the patient's own healing abilities. "The body doesn't reject dermis, the bottom layer of skin," Applegate explains. "By providing the dermis, we're 'reminding' the wounded skin how to regenerate itself, and that jump-starts the healing process."

The fact that Dermagraft's cells are alive when they're applied to the patient made the product's development, manufacturing, and application especially challenging. The product has the consistency of a wet paper towel, and it is very sensitive to fluctuations in temperature and handling.

"You can't tell if the product is still alive by looking at it, so we did all we could to minimize the ways in which it could be damaged," Applegate says. "We grow and sell the product in the same package, which we call a 'bioreactor system,' to reduce handling and to provide physicians with packaging that simplifies use and minimizes potential for product damage, including temperature fluctuations imposed by physicians transporting the product under their armpit or impact damage that would occur if the product were folded in half, pinched, or scraped."

The 'bioreactor system' Applegate refers to simulates the human body. Cells are seeded on a bioresorbable polymer scaffold, fed a nutrient-rich broth, and maintained at 37°C, normal body temperature. Once the product grows to 2 x 3 in. (the size physicians prefer), the tissue is frozen and stored at –70°C, which preserves the product for five months.

In addition to filling an unmet need in the marketplace, the product caters to physicians' needs, says ATS. "We went to great lengths to figure out what doctors wanted and to give it to them with the design of this product," Applegate says. "From color to size, to rinsing the product with easily available saline rather than another solution, to reducing the rinsing time from 30 minutes to less than 1 minute, we've worked to make doctors happy."

Copyright ©2002 Medical Device & Diagnostic Industry