The three-eared mouse is a pretty good emblem of where medical science could take us in the new millennium. The burgeoning field known as tissue engineering didn’t even exist 15 years ago. Today its pioneers are finding that almost any biological material can be coaxed from a culture dish. Bioengineered skin, bone and cartilage are already reaching the clinic. Lab-grown organs, though farther off, are also in the works. And a handful of visionaries are pursuing brain and eye devices that would incorporate both living tissue and electronic gadgetry–A la cyborgs. The day your local tissue lab can grow you a functioning hand or heart is still decades away, but the scenario gets more plausible every week. “In the coming century,” says Dr. Joseph Vacanti, a surgeon at Boston’s Children’s Hospital and a founder of the field, “I think we’ll learn to generate living prosthetics for every organ system in the body.”
The first test-tube tissues to hit the mass market will be “structural” ones, such as skin, bone and cartilage. Several biotech companies are already racing to license skin substitutes that could revolutionize the treatment of burns and other serious wounds. Burns alone place 150,000 Americans in the hospital each year, and 13,000 of those burns are deep enough to require skin grafts. In that procedure, a specialist cuts away dead tissue and covers the exposed viscera with cadaver skin to create a temporary barrier against infection and water loss. As the wounds start to heal, the specialist removes the cadaver tissue and replaces it with thin sheets of skin stripped from other parts of the patient’s body. Unfortunately, cadaver skin is scarce enough that patients may die waiting for it. It also varies wildly in quality, and is quickly rejected by the immune system.
The new lab-grown substitutes address all of those problems. Starting with cells from the foreskins of circumcised infants, engineers can now mass-produce postcard-size sheets of durable, uniform tissue that the body readily accepts. At Advanced Tissue Sciences (ATS) of La Jolla, Calif., technicians grow the cells on biodegradable lattices to produce the functional equivalent of dermis, the thick, inner layer of natural skin. A Massachusetts firm called Organogenesis has brewed a more complete skin substitute, which includes both dermis and epidermis. Both companies have asked the FDA to approve their products as remedies for the deep, nonhealing skin ulcers that cause 75,000 amputations a year among U.S. diabetics. ATS will also market a temporary covering for severe burns–a move that could forever remove the need for cadaver skin. And if Organogenesis’s Apligraf can be adapted to burns, it could spare people the agony of follow-up grafts as well.
While the skin makers strive to make our outer layers replaceable, other researchers are learning to create fully functional bone substitutes. Until recently, the only way to replace missing bone tissue was to borrow it from another part of the body–a painful, expensive and risky proposition–or to try transplanting it from a cadaver. Several companies now sell bone substitutes made from sea coral and other foreign substances, and at least one innovator has gone a step farther, developing grafts that the body can convert into living material.
Working with calcium phosphate, University of Texas chemist Richard Lagow builds structures that approximate the various textures of natural bone. The grafts can be made more or less porous, depending on their intended location. And when surgeons implant these devices, they’re continually broken down and refurbished along with the surrounding tissue. So far only a half-dozen test subjects (all dogs) have received Lagow’s bone substitute, but all have fared well. Implants placed in the animals’ front legs have converted to new bone within three years.
Unlike skin and bone, cartilage doesn’t repair itself spontaneously. But a number of labs can now culture new cartilage from a small sample of cells. Surgeons in the United States and Sweden are using the technique to treat knee injuries. And researchers are discovering that once you can cultivate this and a few other basic tissues, you can build almost anything with them. At MIT and Children’s Hospital in Boston, some of the same scientists who brought us the three-eared mouse are testing an array of more practical inventions. The basic technique, developed by Vacanti of Children’s and chemical engineer Robert Langer of MIT, is to seed a biodegradable scaffold with cells for the needed replacement part. When the structure is bathed in the right nutrients and growth factors for a period of weeks, the cells overrun the scaffolding, creating a ready-to-wear tissue implant.
Researchers have already used the technique to fabricate valves for the heart and the urinary tract. Vacanti and his colleague Christopher Breuer have shown that heart valves grown from blood-vessel cells function normally in lambs. If human trials yield similar results, the 60,000 Americans who now receive troublesome pig valves or mechanical devices each year could soon be growing their own. A Boston company called Reprogenesis has already launched human trials of lab-grown urinary valves and expects to start producing them commercially within two years. The same company hopes to use Langer and Vacanti’s method to generate natural breast tissue (an obvious improvement over saline or silicone implants). And ATS has purchased the rights to market lab-grown facial features. As the MIT mouse showed the world, replacing a damaged ear, nose or eye socket is now theoretically as simple as building a scaffold from an MRI image.
With luck, then, the tissues that hold us together will be fully replaceable within a few decades. Internal organs pose a far greater challenge, but optimists predict that a perfectly functional kidney or liver will someday be cooked up in a lab. An array of organ tissues is already growing in culture dishes, and scientists are finding that even a cluster of critical cells can sometimes save a life. Just ask Don Smith. Unlike virtually any other type I diabetic, the 39-year-old Texan has gone more than three years without an insulin injection. He’s getting enough insulin from 2 million surgically implanted islet cells to eat ice cream with abandon. “As long as I stay away from Cracker Jacks and alcohol,” he says, “I’m fine.”
Smith has an unusual advantage: the anti-rejection drugs he takes to protect a transplanted kidney keep his immune system from attacking the islets. But several labs are now testing a scheme that could make cell implants feasible for anyone. The idea is to encase pig islets in tiny semipermeable beads before implanting them in the gut. Surrounded by a tight synthetic mesh, the cells manage to take in nutrients and pump out insulin while remaining completely walled off from the antibodies and immune cells that would normally destroy them. Researchers at several institutions are now starting or planning human trials.
LIVER CELLS DON’T WORK IN ISOLATION THE WAY ISLET cells do, so Vacanti and his colleagues are striving to grow the entire organ. Their hopes rest on a machine called a 3-D printer, which generates actual objects from images. Like an inkjet printer, the instrument has a head that spits on a surface as directed. But unlike a common printer, it deposits layer after layer of material to create a three-dimensional structure. Linda Griffith, now an MIT faculty member, was studying with Langer and Vacanti several years ago when she met the machine’s inventors. They had designed it for building airplane engines from metal and ceramic, but Griffith thought of scaling it down and using it to build better models for body parts. The trick worked, and she and Vacanti are now growing liver tissue on intricate models of the organ. They have already seen liver cells “differentiate” on the new scaffolds, to form the beginnings of a vascular system. “Making something the size of a lemon could be a lot hard- er than making something the size of a grape,” she says. “But we have the technology.”
Like engineered organs, lab-grown prosthetics for the brain and nervous system are still far in the future. But scientists are learning to cultivate nerve cells, and a few visionaries are designing mechanical substitutes. One of the early entries is LVES (pronounced “Elvis”), an artificial vision system developed from NASA technology by Robert Massof and colleagues at the Johns Hopkins School of Medicine. LVES, officially the Low-Vision Enhancement System, costs about $5,000 and has been commercially available for two years. The device can’t restore sight to the blind, but it can illuminate the world for people with limited vision.
Designed as a pair of goggles, LVES features two wide-angle cameras and a zoom lens, which feed images to a battery-operated waist pack. After magnifying images and adding contrast, LVES projects them onto a pair of goggle-mounted screens. The effect is like that of watching a five-foot TV from a distance of four feet. Future models will offer advanced features, such as freeze frame and instant replay, as well as ports to accommodate video and computer feeds. But LVES will still require at least partial vision. When the eyes can no longer receive data, the question becomes, in Massof’s words, “Where can you plug in?”
Scientists are pursuing at least two possibilities. Researchers at MIT and the Massachusetts Eye and Ear Infirmary are developing a tiny computer chip that would sit on the back of the eye, receiving visual data from a goggle-mounted laser and relaying impulses through the optic nerve to the brain. And researchers led by University of Utah bioengineer Richard Normann are fiddling with a system for mapping camera signals straight onto the brain’s visual cortex. Both systems are decades from completion. But the new work raises the possibility that members of some future generation will have “Gilligan’s Island” reruns beamed directly into their heads.
No matter how good we get at replacing parts of ourselves, whole bodies won’t emerge from tissue labs any time soon: 21st-century babies will still do mandatory time in the womb. Medical technology can’t yet sustain infants born less than 24 weeks after conception. And because their lungs aren’t ready for respiration, those born before 26 weeks rarely survive without complications. But researchers have recently shown that by ventilating a preemie with fluids called perfluorocarbons, they can supply oxygen to the tissues without damaging the lungs. Thanks to liquid ventilation, says Temple University physiologist Thomas Shaffer, fetuses as young as 18 weeks could conceivably finish their gestation in liquid-filled artificial wombs. No one has tried to make one, and there is no pressing reason to try. But that doesn’t mean it won’t happen.
Ear. By constructing a biodegradable scaffold and seeding it with cartilage cells, researchers can generate a ready-to-wear implant. Noses and eye sockets are feasible, too.
Brain. The race is on to restore damaged tissue in various parts of the brain. Implanted cells or growth factors could help reverse many diseases.
Eye. Nobody expects to grow one in culture, but several teams are developing artificial vision systems to be placed inside or outside the head.
Breast. Tissue engineers are developing the tools to grow new breast tissue from a woman’s own cells. Natural implants could make saline and silicone obsolete.
Heart valve. Researchers in Boston have shown that heart valves grown from blood-vessel cells work well in lambs. Lab-grown valves could help 60,000 people a year.
Pancreas. Many diabetics lack the organ’s insulin-producing islet cells. Implants filled with pig islets may free diabetics from insulin injections for periods of several years.
Liver. The cells are balky outside the body, but scientists are learning to generate normal liver tissue in culture. Optimists expect to grow a complete organ within decades.
Womb. Thanks to a new technique called liquid ventilation, fetuses as young as 18 weeks may someday be able to survive suspended in vials of liquid.
Bladder. By growing cartilage in the right mold, bio-engineers can fabricate the valves that keep urine flowing in the right direction. Many children could benefit.
Bone. Several companies now sell bone substitutes made from foreign substances. One researcher is testing grafts that the body gradually replaces with living material.
Cartilage. The glistening white joint lining doesn’t repair itself, but surgeons in the United States and Sweden now use lab-grown cartilage to treat serious knee injuries.
Skin. Several biotech companies have succeeded at growing human tissue in a lab dish. One discarded foreskin can generate enough to help thousands of burn victims.
