Dramatic advances in the fields of biochemistry, cell and molecular biology, genetics, medicine, biomedical engineering and materials science have given rise to the remarkable new cross-disciplinary field of tissue engineering, which uses synthetic or naturally derived, engineered biomaterials to replace damaged or defective tissues in animals or people. Tissue engineering potentially offers dramatic improvements in medical care for hundreds of thousands of patients annually, new therapies for currently intractable problems, and equally dramatic reductions in medical costs.

Emergent (i.e. clinical trials or early market) technologies include encapsulated cells (producing insulin, pain medication), skin substitutes, wound-healing aids, and stem cell bioreactors. Developments in the forseeable future may be blood vessel, cartilage, liver, and cardiac muscle replacement, implantable scaffolds laced with factors encouraging nerve regrowth, bioreactors for growing a wide variety of cells, more effective vaccines, and whole organ xenotransplants.

All in all, it is estimated that tissue engineering solutions potentially could better address diseases and disorders accounting for about half of the nation's total health care costs. The nacent field of Tissue Engineering is already improving health care by providing the first real treatment for serious burns, rather than the palliative therapy which is the industry standard, and providing extracorporeal devices to manage organ failure. A mature Tissue Engineering Industry could carve out new industry sectors by replacing tissues and organs endangered by trauma, disease, or genetic deficiencies; eliminate the morbidity and mortality associated with transplant recipient queues; and developing reliable, "off-the-shelf" diagnostic tools, to name a few.

Several technologies come together in tissue engineering. Culturing of human or animal cells--including bone, cartilage, endothelial, liver, marrow, muscle, nerve, skin, and stem cells--has been demonstrated in proof-of-principal projects. Naturally derived or synthetic materials have been be fashioned into "scaffolds" that when implanted in the body--as temporary structures--provide a template that allows animal (or, in a few cases, human) cells to grow and form new tissues while the scaffold is gradually absorbed. Cells have been engineered to become miniature "bioreactors", secreting therapeutic molecules from within capsules which protect against immune rejection. Transgenic animals have been generated which lay the groundwork for "designer donors" to provide a source of cells, tissues, and organs for long-term xenografts.

Although this early research often has been promising, significant technical challenges remain before products can be brought to clinical trials and subsequent commercialization, including

• techniques to scale up cell culturing to produce commercial quantities of viable cells without introducing contamination or unwantedgenetic 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.

The first tissue engineered products were recently launched (Alloderm^TM, Integra^TM and Dermagraft-TC^TM skin substitutes). Industry support for the initial ATP focused program on tissue engineering (97-07) was expressed in over 50 white papers (representing 80 organizations), and 56 submitted proposals. Debriefings were requested by 80% of the unsuccessful applicants, and many indicated a serious intent to submit proposals to ATP again. Basic research and initial feasibility studies of particularly promising applications have been conducted at numerous academic centers supported by U. S. Government and private funding. Industry attendance and participation at scientific meetings shows not only a continuing commitment, but also slow progress in many key areas related to fundamental issues like biocompatibility.

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, and the requirements for integration of sometimes disparate technologies (like cell biology and materials science) are high. Many of the technical breakthroughs like designing the optimal barrier to immune attack while allowing diffusion of useful molecules are considered too applied for other funding sources (i.e. NIH or NSF). At the same time, technical challenges such as extrapolating a few millimeters of axon outgrowth to full nerve regeneration are too risky for most Venture Capitalists. ATP could (and has) not only accelerated advances in this area, but also provides encouragement to other investors to take on more R&D risk.

Date created: November 1998
Last updated: April 12, 2005