Cyclosporin A encouraged a wave of transplants and also helped set the stage for the current rise in "tissue engineering" as scientists call the construction of whole artificial organs. Transplant surgeons, who no longer lost patients because of the rejection of their transplants, now were faced with a new frustration--losing patients for lack of donor organs. One of those frustrated doctors was Joseph Vacanti at Boston's Children's Hospital, home of the first successful human organ transplant. In 1983, Vacanti began talking with his friend Robert Langer, a chemical engineer at the Massachusetts Institute of Technology, about the feasibility of making an artificial liver and possible other artificial tissues to save the lives of his young patients.

It was a tall order. Nobody had built any kind of working organ, let alone one as complex as the liver. In addressing this task, Langer called considerable experience to bear on attacking the problem in a rational way. In the mid-1970s, he had developed some polymer systems for M. Judah Folkman of Harvard University, who was then investigating the role of new blood vessels in promoting the growth of cancerous tumors, and was looking for a slow-release mechanism to release compounds that block the chemical messengers that control angiogenesis, the formation of new blood vessels. Langer discovered that polymers such as ethylene-vinyl acetate, which absorb very little water, could slowly deliver these chemical messages.

One polymer that Langer eventually focused on was polyglycolic acid, or PGA, which was also used in synthetic degradable sutures and had reached the market in 1970. PGA itself had been known since at least 1950, when Norton Higgins of DuPont patented a three-step process for making it from glycolic acid by carefully manipulating temperature and pressure. The patent Higgins filed did not mention medical applications, but in 1963 Edward Schmitt and Rocco Polistina of American Cyanamid Company filed a patent for the formation of sutures from PGA. When the sutures reached the market seven years later, they were rapidly adopted as a strong, reliable, and workable replacement for the traditional collagen-based absorbable sutures that surgeons had used until then.

Using PGA and similar polymers, Langer crafted degradable and nondegradable polymer pellets into an intricate porous structure that allowed the slow diffusion of large molecules. (This finding is the foundation of much of today's controlled drug delivery technology.) Loaded with chemical messengers, the pellets played a key role in Langer and Folkman's 1975 discovery in cartilage of the first compound that blocks the formation of new blood vessels, thereby halting tumor growth.

In 1984, at about the same time he was approached by Joseph Vacanti, Langer teamed up with Henry Brem, a brain cancer surgeon at Johns Hopkins Medical Institutions, to test his new techniques using polymers against brain cancer. Although there were new tools for finding tumors, including computed tomography and magnetic resonance imaging scanners, the most malignant brain cancers remained largely untreatable. Cancer cells remaining after the tumor's removal were protected from chemotherapy drugs by the so called blood-brain barrier, which prevents a variety of bloodborne chemicals from penetrating the brain. Brem wondered if polymers could slowly release cancer-killing drugs right where they were needed--in the brain itself.

Langer responded by designing surface-degrading polymers that released medicines at a controlled rate. In 1992, Brem and Michael Colvin, now director of the Duke Cancer Center, implanted drug-bearing polymer wafers after brain surgery. The wafers prolonged the lives of both experimental animals and human patients. Since the chemicals were released locally, they did not result in the systemic toxicity typical of anticancer drugs. With FDA approval in 1996, the wafers represent the first new treatment for brain cancer in 25 years. Similar slow-delivery systems are now being used to treat prostate cancer, endometriosis, and severe bone infections.


All these efforts laid the groundwork for researchers' continuing search for a framework for growing replacement body parts and organs, such as livers. By now scientists had learned that human cells grown on flat plates did not produce the normal array of proteins, while cells grown on three-dimensional scaffolds had relatively normal biochemistry. At first the best results were obtained from PGA, but since the best source of fibrous PGA in 1984 was degradable sutures, hours were spent unwinding sutures to transform the fibers into meshlike plastic scaffolds to support liver cells. Still, by 1986, liver cells on plastic frameworks were surviving and functioning after transplantation into animals, laying the groundwork for using polymer scaffolds to create a variety of tissues, from bone to cartilage to skin.

The polymer scaffolds, made with nonwoven fabric techniques borrowed from the textile industry, have now been used to grow at least 25 types of cells in animals or people and have thus become a kind of generic framework for artificial organs. Biotechnology firms are using the scaffolds to make artificial skin for treating diabetic ulcers and severe burns. They multiply living cells in culture (from tissue that is normally discarded during surgery), and then "seed" the cells on the polymer scaffold. Applied to the patient's wound, the material protects against deadly infection and fluid loss. More important, the cells it carries release chemical growth factors, signals that stimulate normal cellular growth at the wound site. These chemicals account for the roughly 60 percent improvement in healing that diabetics like Frank Baker experience with artificial skin. As tissue engineers look to the future, they are talking about using polymer scaffolds to grow nerve cells for use in spinal cord repairs, bone or cartilage cells for joint repairs, pancreatic cells to make insulin for diabetics, and liver cells to make livers for transplantation.

Through all of these efforts by many kinds of scientists, several facts stand out. The path from need to benefit travels through many areas of science and technology and depends crucially on the insights provided by basic research. The first polymer inventors made progress by transforming natural materials in hit-or-miss fashion, but their work greatly accelerated after basic researchers clarified the fundamental characteristics, such as the relation between size or molecular weight and physical properties, that govern the behavior of polymers. Similarly, the progress in medicine and biology that gave birth to organ transplantation still relies on basic research into the role of chemical messengers, genetic codes, and cellular function. As polymer science and materials engineering join forces with biology and medicine to produce these modern miracles, we again see how interdisciplinary collaboration and essential basic and applied research remain the true source of benefits as simple--and profound--as a living tissue that can be created in the laboratory.