Biotech Devices: Replacing Test Animals, Improving Diagnoses : Part 2

by Food and Drug Administration (FDA)

(Page 2 of 2)

Bioengineered Tissue

Recombinant DNA-derived proteins combined with synthetic materials can function as implants. Two companies, Advanced Tissue Sciences in La Jolla, Calif., and Organogenesis, in Canton, Mass., have a variety of such bioengineered tissues in development, with a few in FDA-sanctioned clinical trials.

The basic recipe for a bioengineered tissue is to sculpt a scaffold from a synthetic material that is accepted in the body, and place cells in or on it. These cells secrete substances as they normally would, or they may be genetically altered to overproduce their natural proteins or manufacture entirely different ones, such as growth factors that might help make the implant more acceptable to the body.

"The primary goal of our tissue engineering research is to grow these tissues as replacements for damaged or failing organs. The benefits of this research could positively impact the lives of patients requiring organ transplants as well as those who suffer from diseases or injuries," says Gail K. Naughton, Ph.D., executive vice president at Advanced Tissue Sciences.

Advanced Tissue Sciences' artificial skin, called Dermagraft, has helped more than 70 burn patients so far in clinical trials. A similar product from Organogenesis, called Graftskin, is being tested to replace skin lost during surgery to remove cancers, moles and tattoos.

"Rather than create a new wound by removing skin from another location on the body, surgeons could use biologically equivalent skin that won't be rejected and will promote natural healing," says David J. Leffell, M.D., chief of surgery at Yale University School of Medicine (New Haven, Conn.), where Graftskin is being tested.

Other tissues on the drawing board at these and other companies include liver, connective tissue, bone marrow, and blood vessels. Some bioengineered tissues are already commercially available for use in toxicity testing, in place of animals.

A scaled-down version of an engineered tissue, a cell implant, is a new route to drug delivery, placing cells that naturally manufacture needed substances precisely where they are needed.

The key advantage of a cell implant is that it is "immunoisolated"; its packaging enables the cells to secrete without being detected by the immune system and destroyed. This is done by surrounding cells with a polymer membrane with holes small enough to allow nutrients in and the therapeutic protein out, while excluding the large molecules and cells responsible for immune rejection, according to Seth A. Rudnick, M.D., president of CytoTherapeutics, Inc. in Providence, R.I.

Prime targets of cell engineers are the beta cells of the pancreas. These cells secrete insulin, a peptide hormone that enables glucose (blood sugar) to enter cells, where it is a source of energy. A cell implant would far better mimic the body's continual secretion of insulin than once or twice daily injections and might prevent some of the damage associated with diabetes caused by the on-again off-again delivery of insulin.

The beta cells lie in a portion of the pancreas called the islets of Langerhans. Researchers have been trying to transplant "naked" islet tissue — just cells — for 20 years, with little success, because the immune system attacks them. Throughout the 1970s and 1980s, various biotechnology companies "played with the idea of encapsulating cells to hide from the immune system. But in two to three months, the capsules broke down," says Rudnick.

Several companies, including CytoTherapeutics and BioHybrid Technologies in Shrewsbury, Mass., are working on finding the right mix of casings and cells to engineer the long-awaited "artificial pancreas." Both companies' products are in the animal testing stage, and both say they will apply to FDA for permission to begin clinical trials by 1994. The same companies are exploring using cell implants in the brain to treat Parkinson's disease and in the spinal cord to relieve chronic pain.

Biosensors

Biosensors wed nature to electronics. A biosensor consists of a biological structure that recognizes another biological structure (such as an enzyme, antibody or receptor), plus a mechanism to transduce, or convert, the reaction of biological recognition into an observable signal, such as a voltage change, light emission, or sound.

Many people who have diabetes use a biosensor to monitor their blood glucose (sugar) levels, information needed several times a day to determine the timing of insulin doses. The device, called a glucose meter, resembles a pen and has been on the market since 1988.

The biological component is the enzyme glucose oxidase. A person drips blood onto a disposable test strip, and inserts the strip into the pen. The enzyme binds to glucose in the blood, producing an electrochemical reaction that stimulates electrodes attached to a meter in the pen device. The meter measures the signal, and in 30 seconds, the blood sugar level flashes on a digital display.

In the future, people with diabetes may be treated from within, thanks to combinations of biotechnology devices. Recombinant DNA-derived insulin, or perhaps transplanted beta cells, may be implanted along with a glucose biosensor that controls rate of insulin delivery.

About the Author

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FDA is A United States government body that oversees medical devices, including contact lenses, intraocular lenses, excimer lasers and eyedrops. In the US, these products must be approved by the FDA before they can be marketed.