• Active or completed projects: 26
• Estimated ATP funding: $ 51.1 M
• Industry cost-share funding: $ 68.5 M

Potential for U.S. Economic Benefit. Dramatic advances in the fields of biochemistry, cell and molecular biology, genetics, biomedical engineering and materials science have given rise to the remarkable new cross-disciplinary field of tissue engineering. Tissue engineering uses synthetic or naturally derived, engineered biomaterials to replace damaged or defective tissues, such as bone, skin, and even organs.

Several technologies come together in tissue engineering. Large-scale culturing of human or animal cells—including skin, muscle, cartilage, bone, marrow, endothelial and stem cells—may provide substitutes to replace damaged components in humans. Naturally derived or synthetic materials may be fashioned into "scaffolds" that when implanted in the body—as temporary structures—provide a template that allows the body’s own cells to grow and form new tissues while the scaffold is gradually absorbed. Pancreatic beta cells required to produce insulin may be encapsulated in engineered biomolecular cages that allow them to function normally in a foreign host without triggering immune responses. Biocompatible polymers may be developed to cover implants and shield them from adhesion of circulating proteins that initiate rejection responses. Transgenic animals may provide a source of cells, tissues, and organs for xenografts.

Tissue engineering potentially offers dramatic improvements in medical care for hundreds of thousands of patients annually, and equally dramatic reductions in medical costs. Organ transplants alone present many opportunities because of the significant shortage of donor organs. More than 10,000 people have died during the past five years while waiting for an organ transplant. Infectious agents such as hepatitis C and HIV further complicate the organ transplants, and recipients generally must remain on costly immunosuppressive drugs for the balance of their lives. Outcome studies have shown that the survival rates for major organ transplants are poor despite their high cost. "Engineered" replacement organs could sidestep many of the hazards and problems associated with donor organs, and at lower cost.

For example, 4,166 liver transplants were performed in the United States between 1987 and 1989. At the end of five years, the total medical costs for the survivors and the 1,887 patients who died within the five-year period came to $960 million. Estimates place the cost of an implantable artificial liver, plus attendant surgical procedures, at $50,000, with follow-up costs of $2,000 per year for five years. If so, 4,166 liver patients could be treated for five years at a total cost of $250 million—a savings of $710 million—and with a higher survival rate and better quality of life for the patients. In fact, a tissue-engineered artificial liver is currently under development for temporary use (outside the body) until a permanent donor organ becomes available. Ultimately, it could become an implantable device totally replacing the need for donor organs if the remaining technical obstacles can be overcome. Industry estimates that ATP co-funding would shorten this process by up to five years.

Other equally promising applications include replacement of lost skin due to severe burns or chronic ulcers; replacement or repair of defective or damaged bones, cartilage, connective tissue, or intervertebral discs; replacement of worn and poorly functioning tissues such as aged muscles or corneas; replacement of damaged blood vessels; and restoration of cells that produce critical enzymes, hormones, and other metabolites.

Among the potential economic benefits from advanced tissue engineering technologies, reduced costs due to the availability of less expensive treatments for major medical problems is obvious, but indirect savings and dramatic improvements in treatment outcomes and quality of life for patients may prove to be even more important. Diabetes mellitus, for example, is a seriously debilitating disease affecting more than 14 million Americans. Counting in the secondary illnesses associated with diabetes—including circulatory, retinal, and renal complications leading to blindness, kidney disease, limb amputations, and heart disease—the estimated annual direct and indirect costs of diabetes come to about $120 billion, or more than 10 percent of the nation’s total annual healthcare costs.

Many of these secondary illnesses are associated with the wide swings in blood glucose levels associated with current therapies. An "artificial pancreas" created by tissue engineering that reproduces the instantaneous response of the normal pancreas to changing glucose levels would dramatically lower the occurrence of these secondary illnesses and, not incidentally, dramatically improve the lives of diabetes sufferers. Such a device has been demonstrated experimentally, but significant research issues remain in extending the technology to commercial scales. If we put the cost of a successful artificial pancreas at $20,000, the annual healthcare costs for diabetes and its secondary effects could be reduced 10- to 20-fold.

All in all, it is estimated that tissue-engineering solutions potentially could address diseases and disorders accounting for about half of the nation’s total healthcare costs.

Technology Challenge and Industry Commitment. Industry support for the ATP focused program on tissue engineering is expressed in over 50 white papers. Basic research and initial feasibility studies of particularly promising applications have been conducted at numerous academic centers supported by the National Institutes of Health, the National Science Foundation, the Pugh Foundation, the American Red Cross, and the Howard Hughes Foundation, among others.

Although this early research often has been promising, significant technical challenges remain before the technologies can be commercialized and the nation can reap the benefits. In particular, several basic enabling technologies must be developed:

• techniques to scale up cell culturing to produce commercial quantities of viable cells without introducing contamination or genetic changes to the product;
• techniques for long-term tissue and cell storage to make products globally available in varying environmental conditions;
• technologies for the efficient manufacture of biocompatible materials from chemical synthesis or transgenic plants and animals;
• tissue-engineered products with chemical or physical properties needed to inhibit potential adverse reactions by the host; and
• universal-donor cell lines with multiple potential uses that are non-immunogenic in humans.

Significance of ATP Funds. Tissue engineering is a technology just emerging from basic research. Many of the companies now involved are small—often start-ups—and the research risks posed by the early technical barriers are high. ATP support targets basic underlying technologies that industry will need to make possible artificial organs, xenografts, and other dramatic tissue-engineering therapies of the future. The ATP Tissue Engineering Program provides a focal point for U.S. research in this field, promoting and strengthening industrial alliances among companies with complementary ideas and technical capabilities.

The ATP focused program in tissue engineering addresses:

• innovative technologies in biomaterials, including the design and production of both biocompatible synthetics and naturally derived biomaterials;
• cellular components, including techniques for large-scale culturing of human and animal cells and the development of transgenic animals as a source of cells and tissue;
• manufacturing processes, including technologies to enhance and scale up production of new tissue-engineered products to help ensure that the new therapies are available to a large patient population at reasonable cost; and
• implantation/transplantation technologies, including devices and tests to monitor transplantation and implantation procedures and to assure the performance of the transplants/implants, as well as the storage technologies needed to make tissue-engineering therapies available on a global basis in widely varied environments.

The ATP focused program specifically does not address the development of non-biological implants such as the metal or plastic valves, joints, pacemakers and other devices currently in clinical use.

Additional Information. For information about eligibility, how to apply, and cost-sharing requirements, contact the Advanced Technology Program:

(800)-ATP-FUND (800)-287-3863
http://www.atp.nist.gov
email: atp@nist.gov
fax: (301) 926-9524
A430 Administration Building
National Institute of Standards and Technology
Gaithersburg, MD 20899-0001

For technical information, contact:
Mrunal Chapekar, ATP Program Manager
(301) 975-6846
e-mail: mrunal.chapekar@nist.gov
fax: (301) 548-1087

Date created: January 1999
Last updated: April 12, 2005