Tissue Engineering

Biology 103
2000 Third Web Report
On Serendip

Tissue Engineering

Nimia Barrera

Imagine a day when people with liver failure can be cured with implanted "neo-organs" made of liver cells and plastic fibers. Imagine a day when insulin-dependent diabetics will not have to take frequent insulin injections because they have semi-synthetic replacement pancreases. A place in time when kidney dialysis machines are obsolete because anyone with damaged kidneys can be outfitted with new ones grown from their very own cells(1). Sound like science fiction? Not to scientists working in tissue engineering, a field of science that is barely a decade old.

Tissue engineering is a new field with a relatively simple concept: you start with some building material (e.g., extracellular matrix, biodegradable polymer), shape it as needed, seed it with living cells and bathe it with growth factors. When the cells multiply, they fill up the scaffold and grow into three-dimensional tissue, and once implanted in the body, the cells recreate their intended tissue functions. Blood vessels attach themselves to the new tissue, the scaffold dissolves, and the newly grown tissue eventually blends in with its surroundings (2). Tissue engineering uses synthetic or naturally derived, engineered biomaterials to replace damaged or defective tissues, such as bone, skin, and even organs (3).

Some people call it "the seaweed that's changing medicine" (4). A combination of cultured cells and special polymers are being used to grow tissue. This began with surgeon Joseph Vascanti of Harvard Medical School and biomedical engineer Robert Langer of the Massachusetts Institute of Technology (4). They had been trying for more than a year to devise new ways to grow thick layers of tissue in the laboratory - a first step toward their long-term goal of growing replacements for damaged tissues and organs. Their success began when they made the connection: branching is nature's way of maximizing surface area to supply thick tissue with nutrients, and polymer materials that branch, rather than staying completely solid, would be porous enough to support growing tissue in the lab(4).

Today, thanks to this realization and the continuing research in this field, some of the simpler tissues, including skin and cartilage, have already made their way into clinics. Furthermore, fueled by recent advances in polymer chemistry, in the design of the bioreactors that incubate tissues, and in the understanding of basic cell and tissue biology, researchers are also beginning to grow organs with more complex architecture.

Every day thousands of people of all ages are admitted to hospitals because of the malfunction of some vital organ. Because of a dearth of transplantable organs, many of these people will die. In perhaps the most dramatic example, the American Heart Association reports only 2,300 of the 40,000 Americans who needed a new heart in 1997 got one (5). Lifesaving livers and kidneys likewise are scarce, as is skin for burn victims and others with wounds that fail to heal. It can sometimes be easier to repair a damaged automobile than the vehicle's driver because the former may be rebuilt using spare parts, a luxury that human beings simply have not enjoyed.

An exciting new strategy, however, is poised to revolutionize the treatment of patients who need new vital structures: the creation of man-made tissues or organs, known as neo-organs. In one scenario, a tissue engineer injects or places a given molecule, such as a growth factor, into a wound or an organ that requires regeneration. These molecules cause the patient's own cells to migrate into the wound site, turn into the right type of cell and regenerate the tissue (5). In the second, and more ambitious, procedure, the patient receives cells - either his or her own or those of a donor - that have been harvested previously and incorporated into three-dimensional scaffolds of biodegradable polymers, such as those used to make dissolvable sutures (5). The entire structure of cells and scaffolding is transplanted into the wound site, where the cells replicate, reorganize and form new tissue. At the same time, the artificial polymers break down, leaving only a completely natural final product in the body - a neo-organ. The creation of neo-organs applies the basic knowledge gained in biology over the past few decades to the problems of tissue and organ reconstruction, just as advances in materials science make possible entirely new types of architectural design.

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 (3).

Needless to say, tissue engineering branches out into many different fields. It is no wonder that so many companies are investing in researching and developing this new field. Mayo Clinic, Selective Genetics, M. D. Anderson Cancer Center, and Genzyme Tissue Repair are just a few of the many companies that are currently involved in this type of research. But what goes into this? Researchers must answer these questions: What specific concentrations of the molecules are needed for the desired effect? How long should the cells be exposed? How long will the factors be active in the body? Certainly multiple factors will be needed for complex organs, but when exactly in the development of the organ does one factor need to replace another? Controlled drug-delivery technology such as transdermal patches developed by the pharmaceutical industry will surely aid efforts to resolve these concerns (5).

Ten millennia ago the development of agriculture freed humanity from a reliance in whatever sustenance nature was kind enough to provide. The development of tissue engineering should provide an analogous freedom from the limitations of the human body (5).

WWW Sources

1)The Promise of Tissue Engineering, Scientific American

2)Tissue Engineering, FIBROGEN Website

3)ATP Focused Program: Tissue Engineering, ATP Website

4)Tissue Engineering: Lab-Grown Organs Begin to Take Shape, Science Magazine

5)Growing New Organs, Scientific American