by Sally Pobojewski
In a bionic world, people would be more like automobiles. When original equipment
started to wear out, your doctor could just pull a new part off the shelf and
plug it in. Getting a new heart would be as easy as getting a new fuel pump.
And no one would have to die waiting for an organ transplant.
Plug-and-play replacement organs may seem far-fetched, but they could be closer
than you think. Bionics — a merger of medicine and engineering where
metal and plastic are just as important to the functioning of the human body
as blood and tissue — has made major advances in the last 50 years.
Prosthetic implants for hips, knees and other damaged joints are helping people
with arthritis maintain active, healthy lifestyles. Cochlear implants are making
it possible for children with profound hearing loss to be educated in a regular
classroom. Mechanical heart-assist pumps are helping people with end-stage
heart disease stay alive until a transplant heart is available. With the widespread
use of contact lenses, breast implants, cardiac pacemakers and heart valves,
there aren’t many of us departing this world today with the same equipment
we had coming in.
The University of Michigan Medical School has been a major player in the fast-moving
field of bionics. Technology developed by U-M scientists has saved the lives
of thousands of desperately ill people and improved the quality of life for
many more. The Medical School is best known for its pioneering work in life
support technology known as ECLS or ECMO, which is used worldwide in intensive
care units to treat patients with acute lung or heart failure.
Today, scientists in the Medical School are testing the world’s first
bionic lung in research animals. A bioartificial kidney and artificial liver
support system are in human clinical trials. Scientists at the U-M’s
Kresge Hearing Research Institute are studying how the brain perceives sound
and the effect of drugs on the inner ear — research that could lead to
a new generation of bionic devices for people with hearing loss. Others in
the Medical School are implanting heart-assist pumps, inserting tiny telescopes
inside the eye, building better bionic joints and developing gene therapy to
heal broken bones.
Who knows what the future will bring? Maybe that heart-on-the-shelf idea isn’t
so crazy, after all.
Preserving Life Outside the Body
Bob Bartlett Photo:
Watching a patient die is the hardest part of being a doctor, but sometimes
all that anger and frustration gets channeled in positive directions. Much
of the lifesaving medical technology we take for granted today was invented
by physicians who were tired of standing by helplessly as their patients
died and decided to do something about it.
This was the case for a group of surgeons at Children’s Hospital in
Boston in the mid-1960s. Frustrated by their inability
to help children who were dying from acute heart or lung failure, they created
a new kind of technology, which they called extracorporeal, or outside-the-body,
membrane oxygenation or ECMO. One of those surgeons was a young resident named
Robert H. Bartlett (M.D. 1963), who is now a professor of surgery in the Medical
School and director of surgical intensive care for the U-M Health System.
Implantable Miniature Telescope
Surgically implanted inside the eye, the IMT can improve vision in people
with severe macular degeneration. Manufactured by Vision Care Ophthalmic
Technologies, Inc. U-M clinical trial directed by Paul Lichter (M.D.
1964, Residency 1968), F. Bruce Fralick Professor of Ophthalmology; chair,
U-M Department of Ophthalmology and Visual Sciences; and director, U-M
Kellogg Eye Center.
HeartMate Left Ventricular Assist Device
Cardiologists at the U-M Health System found that this implantable
heart-assist pump helped heart patients, who were waiting for
a transplant or were
too ill to receive one, survive for more than a year. Manufactured by
Thoratec Corporation. U-M clinical trials directed by Francis Pagani,
M.D. (Residency 1996), Ph.D., associate professor of surgery.
DeBakey Ventricular Assist Device
In February 2003, Eric Devaney, M.D., assistant
professor of cardiac surgery, implanted this miniature heart pump in
a 10-year-old girl —the
youngest child to receive the device. Manufactured by MicroMed Technology,
Gene Activated Matrix Technology
An implantable, biodegradable scaffold
to deliver DNA for site-specific gene therapy to heal damaged bones,
heart muscle and skin. Manufactured
by Selective Genetics, Inc. Technology developed by Steven A. Goldstein,
Ph.D., Henry Ruppenthal Family Professor of Orthopedic Surgery and Bioengineering,
and Jeffrey Bonadio, M.D., former U-M Medical School faculty.
Ceramic-on-Ceramic Total Hip Replacement
Ceramic-on-ceramic total hip
replacements demonstrate less wear than the metal-on-plastic implants
used previously. Orthopaedic scientists
predict that the lower wear will translate into longer service life even
in patients with higher functional demand. The U-M Health System was
the first Michigan hospital to offer the new implant to patients after
its approval by the Food and Drug Administration on February 3. U-M orthopaedic
surgeons: Andrew Urquhart (M.D. 1991, Residency 1996), assistant professor
of orthopaedic surgery, and J. David Blaha, M.D., of the Division of
Adult Reconstructive Surgery. Manufactured by Stryker Howmedica Osteonics
and Wright Medical Technology.
Medial Pivot Knee Joint Prosthesis
An artificial knee to restore joint function
in people with osteoarthritis or other types of joint damage. Manufactured
by Wright Medical Technology.
Surgeon designer: J. David Blaha (M.D. 1973, Residency 1978), clinical
professor of orthopaedic surgery.
The idea was to create a modified version of a heart-lung bypass machine — a
new device that could take over temporarily for hearts or lungs damaged by
infection, trauma or shock — giving them time to rest and recover until
they regained their ability to function. In essence, the machine would breathe
for the patient. Blood would be pumped out of the body, through a filtering
device to remove carbon dioxide and add oxygen, and then would be returned
to the patient.
At first, the researchers were optimistic. After all, they used heart-lung
bypass machines during surgery all the time. How hard could it be to use the
same basic procedure for several days, instead of several hours? Unfortunately,
it turned out to be very hard. The longer research animals used in early experiments
remained on the device, the more lethal complications they developed. As soon
as the scientists solved one technical problem, there was another one to take
“During the late 1960s and 70s, most people thought artificial lung
technology was unnecessary, crazy or just wouldn’t work,” says
Bartlett — a self-effacing man who chooses his words carefully and would
much rather talk about the accomplishments of his colleagues or former students,
instead of his own. “Today it’s a well-established and accepted
technology, especially for infants and children with lethal pulmonary or cardiac
failure where the lung or heart is expected to recover.”
In 1975, when the National Institutes of Health sponsored the first clinical
trial of the new technology, the survival rate in adults with severe respiratory
failure was only 10 percent. When Bartlett brought his research program to
the U-M Medical School in 1980, he had used the technology successfully only
with a handful of critically ill newborns and very young children with acute
Thanks to research advances and improved technology, the picture is much brighter
today. A survey of Health System patients treated between 1980 and 1998 with
what is now called ECLS, or extracorporeal life support technology, showed
that 56 percent of adults with acute respiratory failure recovered and were
discharged from the hospital. The success rate in newborn infants and young
children was even better. Eighty-eight percent of newborns with neonatal respiratory
failure survived, as did 70 percent of children treated during the same time
period. Lungs of newborns and children recover faster, so ECLS is more effective
and produces fewer complications in children than in adults.
“The U-M Health System has the largest and most diverse experience with
ECLS technology in the world,” Bartlett says. “The technology has
expanded from Michigan to 120 centers worldwide. It’s standard care in
every children’s hospital, but still isn’t used often or soon enough
with adults in intensive care units.”
Unfortunately, ECLS offers no hope to millions of people in the U.S. with
chronic, rather than acute, organ failure. These are people with cystic fibrosis,
emphysema, hepatitis, and end-stage heart or kidney disease whose condition
will deteriorate gradually over time. Some wait years for transplant organs,
often dying before a suitable organ is found. Others live with the debilitating
side effects of long-term kidney dialysis or progressive heart or liver failure.
To help patients with chronic lung disease, Bartlett and U-M colleague Ronald
Hirschl (M.D. 1983, Residencies 1989, 1991), an associate professor of surgery,
have developed an artificial lung which is now being tested in sheep. Called
the MC3 BioLung, it was designed and is produced by MC3 — Michigan Critical
Care Consultants, Inc. — an Ann Arbor research and development firm started
12 years ago by Bartlett and two of his graduate students. Bartlett recently
received a $4.8 million, five-year grant from the National Institutes of Health
to complete animal studies and develop the artificial lung to the point where
it can be tested in people.
Using the pumping power of the sheep’s heart, the BioLung attaches to
the pulmonary artery and replaces 100 percent of normal lung function. The
one-pound device can be used outside the body or implanted inside the chest
wall. Blood passes through one side of a cartridge divided by a thin, permeable
membrane. Oxygen flows through the other side. As blood flows through the device,
carbon dioxide and oxygen diffuse through the membrane. Reoxygenated blood
is then returned to the animal.
“We are now at the point where we can use the lung for a week at a time
in healthy sheep,” Bartlett says. “When we can extend that time
to about a month, we will start preparing for a clinical trial in seriously
ill patients who are candidates for a lung transplant. Our hope is that the
device will sustain them long enough to find a donor.”
Progress with the artificial lung encouraged Bartlett and his research team
to start work on an artificial liver life support system, which could buy time
for the approximately 18,000 people in the United States with end-stage liver
disease who are waiting for a transplant. “Our hope was that it could
be used to treat chronic liver failure, much as hemodialysis is used for chronic
kidney failure,” Bartlett says.
The human liver is a complex, multi-function organ and replacing it, even
for a few days or weeks, is a daunting challenge. Not only does the liver remove
toxic substances from blood, it also produces important proteins that regulate
metabolism, blood clotting and the immune response.
“The liver can regenerate itself, but it stops regenerating in the midst
of severe liver failure,” Bartlett explains. “One of our research
fellows, Sam Awad, demonstrated that if you remove all the toxic material from
blood, the liver cells get better. So we developed a system, tested it in animals
and started a clinical trial in 1998.”
Results of the first test of Bartlett’s artificial liver with 20 acutely
ill patients were encouraging. The treatment helped six patients improve and
remain healthy enough to receive a liver transplant. Three of those patients
are still living today. Two patients recovered liver function and left the
hospital without needing a transplant. “That was unexpected and very
positive,” Bartlett says. “We actually had donors for those patients,
but they were doing so well, we decided against a transplant.”
Eager to share news of their success, Bartlett’s research team presented
preliminary results at a symposium in Germany where they met scientists from
a German firm called Teraklin AG. Teraklin scientists were reporting encouraging
results from their artificial liver support system, which was already being
used to treat patients in Europe. The German system was called MARS for molecular
albumin recycling system.
“The Teraklin device used the same principles and concepts, but a few
of the technical details and materials used to remove toxic compounds from
blood were different,” Bartlett says. “It was different enough
that we knew the device would work better than our version.”
So Bartlett made it his business to help Teraklin AG obtain approval from
the U.S. Food & Drug Administration to use the MARS system in the United
States. As part of that process, the U-M Health System is currently participating,
with four other medical centers, in a phase III clinical trial to compare the
effectiveness of the MARS artificial liver system against standard medical
treatment. The trial will enroll 75 patients with chronic liver failure who
are so sick they are in what doctors call a hepatic coma. U-M physician Robert
Fontana (M.D. 1988), an assistant professor of internal medicine, is directing
the clinical trial.
“We are anxious to have MARS technology approved by the FDA,” Bartlett
says. “Then we will go to work trying to improve it, which the people
in Germany are working on, too. We have become good friends and we’re
working on all these projects together. We’re not in the business of
competing. We’re in the business of doing what’s best for the patient.”
Bartlett has treated patients in intensive care whose heart, lungs, liver
and kidneys were all being supported simultaneously by different extracorporeal
devices. “Interlocking the devices is not much of a problem, because
they all come in standard sizes,” he says. Eventually Bartlett expects
to see a universal blood-processing device with plug-in modules or cartridges
for different applications. Implantable devices will never be one-size-fits-all,
however, because human anatomy varies too much from person to person.
No matter how advanced the technology, all ECLS devices have the same fatal
flaw: Whenever blood is exposed to anything other than endothelial cells lining
the inside of blood vessels, it tends to clot. And even tiny blood clots developing
in a piece of plastic tubing or on a pump’s metal surface can kill the
“It’s necessary to use medications like heparin, which cause bleeding
in the patient, to prevent clotting,” Bartlett says. “Balancing
the risk of clotting with the risk of bleeding is the biggest problem in any
type of artificial organ implantation. Clotting starts with blood platelets,
so if we could stop platelets from sticking to surfaces, we could prevent clots
For seven years, Bartlett has been working with Mark Meyerhoff, U-M professor
of chemistry, to develop the ideal prosthetic surface — a polymer on
which blood won’t clot. Meyerhoff’s polymers contain tiny silica
particles that release low levels of nitric oxide gas — the same gas
produced by human endothelial cells to relax blood vessels and inhibit coagulation.
Research in Bartlett’s lab showed that the new polymer eliminated the
need for heparin in research animals during ECLS procedures.
“Once we have plastic surfaces that prevent platelets from sticking,
the entire field of artificial organs will change dramatically, because the
clotting problem is the major limiting factor,” Bartlett says. “This
is where the research focus is directed now. We still have some technical obstacles
to overcome, but I think we are very close to solving the problem.”
Building a Bioartificial Kidney with Living Cells
David Humes with renal-assist technology Photo:
More than 300,000 Americans with kidney disease are alive today because they
spend several hours every week connected to a renal dialysis machine. During
dialysis, the patient’s blood flows through hollow fibers, which remove
toxic waste products normally filtered out by healthy kidneys.
But long-term use of dialysis creates its own set of problems — heart
attacks, strokes, blood clots, infection — that kill patients just as
surely as kidney disease does, says H. David Humes, M.D., a professor of internal
medicine in the Medical School.
“If you are a 59-year-old man and go on dialysis, your average predicted
mortality is four years,” Humes says. “Your chances of living longer
are better if you are diagnosed with prostate or colon cancer, as opposed to
end-stage renal disease on dialysis.”
Humes thought there must be a better way to help patients with serious kidney
disease other than filtering their blood through what he calls “a dead
synthetic membrane.” He developed a new device made of hollow fibers
lined with a type of kidney cell called renal proximal tubule cells. These
cells reclaim vital electrolytes, salt, glucose and water, as well as control
production of immune system molecules called cytokines, which the body needs
to fight infection. Conventional kidney dialysis machines remove these important
components of blood plasma, along with toxic waste products, and cannot provide
the cytokine regulation function of living cells.
In 1995, Humes started a company called Nephros Therapeutics, Inc., to develop
and market his new technology. Today, instead of animal cells, Nephros scientists
use cells from human kidneys donated for transplant — kidneys that cannot
be used because they have anatomical defects or scarring. The kidneys are processed
to remove progenitor cells, similar to adult stem cells, which are capable
of forming millions of proximal tubule cells when grown under the right conditions
in a special blend of growth factors, nutrients and proteins. The cells grow
to cover the inside of hollow fibers — 4,000 of which are packed in cartridges
and used in conjunction with a conventional hemodialysis filter to create what
Humes calls a bioartificial kidney.
“These progenitor cells are real miracle cells,” Humes says. “With
all the manipulation we put them through, they remain vigorous, robust and
able to function as if they were still inside the body.”
Nephros Therapeutics recently completed a clinical trial to test the safety
of the renal assist device in 10 critically ill patients with acute renal failure
at the U-M Health System and the Cleveland Clinic. The company has applied
for FDA approval for a follow-up study in six academic medical centers that
began in August. Eventually, Humes hopes to test the effectiveness of his bioartificial
kidney against dialysis in patients with chronic renal failure and to develop
an implantable version that can be used inside the body.
“Nobody believed our renal assist device would work,” Humes says. “Until
there’s a success story, people are very skeptical. But whenever I was
discouraged, all I had to do was talk to patients. Knowing how badly these
people suffer gives you sustaining power to move forward in what may appear
to be unconventional therapy.”
Implanting a World of Sound
Cochlear implants are one of bionic technology’s greatest success stories.
Today, thousands of people with significant hearing loss rely on cochlear implants — electronic
devices that fit inside the cochlea of the inner ear and make it possible for
even the profoundly deaf to hear.
“Results with today’s cochlear implants are exceeding any expectations
we had when I started in the field 20 years ago,” says Teresa Zwolan,
Ph.D., an associate professor of otolaryngology and director of the U-M’s
Cochlear Implant Program. “Years ago you had to be profoundly deaf to
be a candidate for an implant. But the technology has improved so much and
patients are doing so well with them that even adults and children who receive
minimal benefit from hearing aids are eligible for a cochlear implant.”
Bryan Pfingst, John Middlebrooks and Josef Miller
with an oversized model of the external, middle and inner ear, photographed
through the window of a sound-attenuating chamber.
Photo: Martin Vloet
Back in the 1960s, Josef Miller, Ph.D., a scientist in the U-M Kresge Hearing
Research Institute, first heard researchers from the House Ear Institute in
Los Angeles describe their early prototypes of a cochlear implant. “Every
scientist at that meeting — including me — threw up their hands
and said ‘this will never work,’” says Miller, a professor
of otolaryngology in the Medical School. “That was 40 years ago. And
we were all wrong. We were dead wrong.
“The nervous system really outsmarted us,” Miller adds. “It
was so good that even though we were only able to do a primitive job, the nervous
system was clever enough to interpret our crude information and make use of
it. Implants at that time were single-channel devices with poor quality information,
but people could hear a car horn and other environmental sounds. It was a remarkable
improvement in their quality of life.”
With current technology, people not only hear car horns, they can hear a conversation — often
even over the telephone. More than 40,000 people around the world use cochlear
implants, and nearly 1,000 of them received those implants at the U-M Health
System. Established in 1984, the U-M’s Cochlear Implant Program has made
the Health System one of the top four centers for cochlear implants in the
U.S., participating in clinical trials for every commercially available device
on the market today.
Teresa Zwolan and Steven Telian Photo: Martin Vloet
Recently the FDA approved the use of cochlear implants for infants as young
as 12 months old. “The research is very strong that the younger children
are when they receive an implant, the better they do,” Zwolan says. “With
aggressive therapy, children who receive implants at 12 months probably will
be fully mainstreamed with normal-hearing children by the time they start kindergarten.
But the longer you wait, the poorer the prognosis.”
Zwolan adds that there is still some controversy associated with the use of
cochlear implants. When the technology was first introduced, many members of
the deaf community who use sign language to communicate were strongly opposed
to the use of implants. Although opposition has lessened over the years, Zwolan
says she is careful to make sure parents know the controversy exists.
“Ninety-five percent of children born deaf are born to parents with
normal hearing,” she says. “If hearing parents have a deaf baby,
they don’t know how to communicate with their child. The cochlear implant
provides a means for letting them communicate without having to learn a completely
new language. In our view, the decision [to get an implant] needs to be a parental
choice that fits the family’s lifestyle.”
In a normal ear, vibrations from sound waves striking the eardrum are transferred
to fluid inside a snail-shaped bony organ called the cochlea deep in the inner
ear. When this fluid moves, it stimulates thousands of hair cells, which line
the inside of the cochlea. When hair cells move, they create neural impulses,
which are picked up by auditory nerve fibers and carried to a part of the brain
called the auditory cortex. The auditory cortex sends these signals to other
areas of the brain where they are processed and interpreted allowing us to “hear” the
signals as sound.
If hair cells are damaged or missing, they cannot generate signals the brain
needs to perceive sound. So implants with tiny stimulating electrodes, inserted
inside the cochlea, substitute for damaged hair cells by producing electrical
signals that travel through the auditory nerve to the brain. After a brief
training period, most people — especially those who lost their hearing
after they learned to talk — can recognize and understand what they hear.
Implanting the device is a delicate microsurgical procedure that takes an
experienced surgeon from 90 minutes to three hours, according to Steven A.
Telian, M.D., professor of otolaryngology and medical director of the U-M Cochlear
Implant Program. “First, we make a recessed area in the mastoid bone
behind the ear to hold the electronic receiver/ stimulator,” Telian says. “Then,
we drill an opening into the cochlea and insert the electrode. To access the
cochlea, we have to work right next to the facial nerve, so the surgeon has
to compromise between being able to see well and making sure the nerve is not
Cochlear implants can’t help people without an auditory nerve, which
carries sound from the ear to the brain. For people without an auditory nerve,
there’s a new type of technology called an auditory brainstem implant. “Instead
of a string of electrodes placed in the cochlea, there’s a patch of electrodes
placed on part of the brainstem called the cochlear nucleus,” says Telian. “The
sound perception is much less reliable and clear than with a cochlear implant,
but it does give people who otherwise would be completely deaf some degree
of sound perception.”
Even though today’s cochlear implant technology is very good, Medical
School researchers are trying to make it even better. David J. Anderson, Ph.D.,
a professor in the U-M College of Engineering and a professor of otolaryngology
in the Medical School, is working with scientists at Cochlear Corporation — a
major manufacturer of cochlear implants — to develop electrode arrays
produced with advanced photolithography technology, instead of by hand. In
addition to better quality control and lower production costs, which could
help reduce the high costs of implants, Anderson says photolithography will
make it possible to produce implants with more electrodes in closer proximity
to auditory nerve cells.
Bryan E. Pfingst, Ph.D. and John C. Middlebrooks, Ph.D., both professors of
otolaryngology and scientists at U-M’s Kresge Hearing Research Institute,
are studying sound perception and how the brain’s auditory cortex processes
signals it receives from the auditory nerve. By analyzing auditory signal processing,
they hope to overcome one of the limitations of current implant technology — the
inability to transmit changes in voice pitch or tone.
“Tone languages like Chinese use rising or falling intonation and high
or low pitch to carry important syntactic information,” Middlebrooks
says. “One-quarter of the world’s population speaks tonal languages,
so if the implant cannot transmit pitch information, that is a serious concern.”
Pfingst and Middlebrooks study guinea pigs with cochlear implants that have
tiny recording electrodes implanted near auditory neurons in their brains.
Using food rewards, technicians train the guinea pigs to respond to sounds
by pushing a button on the floor of their cage. “We study how the animals
perceive sound by asking them to discriminate between different sounds or tones
played on different channels in their implant,” Pfingst says.
In another study, Josef Miller and Richard A. Altschuler, Ph.D. — a
professor of cell and developmental biology and professor of otolaryngology
in the Medical School — found that inserting substances called growth
factors into the inner ears of deafened guinea pigs can prevent auditory nerve
cells from dying and stimulate the growth of healthy, functioning nerve fibers,
which are vital to successful use of a cochlear implant.
Miller is scientific director of a $3 million European research program called
BioEar. The goal is to develop the first drug delivery system for use with
a cochlear implant. A human clinical trial is scheduled to begin late in 2004,
which will be the first study testing the effects of delivering drugs continuously
to the human inner ear.
“We want to induce the nerves of the inner ear to grow out to and make
intimate contact with individual electrodes of this next-generation cochlear
implant,” Miller explains. “It’s not just a better implant;
it’s really tissue engineering the inner ear.”