Researchers work to create medical implants that bodies won’t reject

Bioengineering/Chemical Engineering Professor Buddy Ratner holds a common medical implant, a vascular prosthesis. Photo by Mary Levin.

As Catharine Talbot-Lawson’s lifelong hearing loss faded toward complete deafness, her world was silently turned upside down.

A nurse of 28 years, Talbot-Lawson was forced to give up her job in the UW Medical Center’s intensive care unit because she could no longer hear the patient alarms. She wasn’t able to talk on the telephone with her parents or other out-of-town friends and relatives. And, though it broke her heart, she avoided taking care of her grandchildren by herself.

“I was afraid to be with them alone,” she says. “I would constantly worry if they were in the next room that they might be hurt and crying and I wouldn’t be able to hear them.”

Over the years, Talbot-Lawson used stronger and stronger hearing aids to maintain a successful career and pursue hobbies like sky diving. But by 1995, the hearing aids were no longer effective. She was faced with the choice of taking disability retirement and learning to live with deafness or getting a cochlear implant—a prosthetic replacement for the inner ear—to restore some of her hearing.

Talbot-Lawson received her implant a year ago and sings its praises in sweet notes that even she can now hear.

“The quality of my life has improved so vastly; I feel like I’m part of the world of the living again,” she says.

But Talbot-Lawson knows her world could slip into silence again. Over time, the cochlear implant may be crippled by her body’s own defense system. Her cells will identify the implant as a foreign object and they’ll wall it off with scar tissue, which eventually could block the electronic signal that stimulates hearing.

Similar problems affect pacemakers, vascular grafts, artificial eye lenses and other medical implants that save or improve the lives of millions of people every year but may provide only temporary relief. The body’s natural reaction to foreign materials too often disrupts the performance of medical implants and requires another operation or other medical attention.

A group of engineers, scientists and doctors at the UW aims to change that. Armed with a five-year, $12.4 million grant from the National Science Foundation, they are trying to develop a new generation of medical implants that mimic the biology of the body parts they replace.

Out of 117 proposals, the University of Washington Engineered Biomaterials (UWEB) project was one of only four engineering research centers funded this year by the National Science Foundation. The UW joins an elite group of 25 universities nationwide selected to lead ground-breaking research in critical areas of discovery, an achievement applauded by new Engineering Dean Denice Denton.

The project is expected to last 11 years with potential funding of $25 million from the National Science Foundation and more than $30 million from industry partners, private foundations and the University.

“The University of Washington is a recognized leader in bioengineering, and with the UWEB engineering research center, we have the makings for a revolution in medical implant technology,” says Buddy Ratner, professor of bioengineering and chemical engineering, who is directing the project.

“We know the human body has the capacity to heal wounds. What we hope to do is develop a new generation of implanted medical devices made of biomaterials that are recognized by cells in the body and that actively trigger the natural healing process.”

The potential for improving patient care is staggering, according to Harborview Surgery Professor Timothy Pohlman, co-investigator in the biomaterials project.

Every year, doctors implant more than a half billion medical devices in patients, only to watch the body’s natural defenses render many of the implants useless. Vascular grafts used to bypass clogged arteries almost always become blocked with scar tissue. Orthopedic hips and knees used to replace joints often become loose and incapable of supporting weight. And catheters—used to deliver drugs or fluids intravenously and by far the most common medical implant—become infected and have to be removed.

UW researchers hope to examine what’s happening at the molecular level to cause these problems, as well as what occurs in normal healing. Once they understand the molecular process, they can cultivate new bionic biomaterials for making medical implants that promote healing. If the body’s natural reaction to foreign materials is overcome, Pohlman says, doctors and scientists envision treatments for a host of maladies that today disrupt or destroy people’s lives.

An implantable glucose monitor could continuously monitor blood-sugar levels in diabetics so they no longer have to do finger-prick tests several times a day or risk the debilitating results of insulin imbalances. Patients with kidney failure, who now have to be hooked up to a dialysis machine on a regular basis to clean their blood while they wait for a kidney transplant, could have a small dialysis machine implanted in their body. They would no longer need a transplant. And Bo Jackson, whose budding NFL career came crashing to a halt when he had to have hip replacement surgery, could return to the football field again with an artificial joint every bit as strong as the real one.

“If you let your mind wander, the opportunities to restore life or function for patients is endless,” Pohlman says. “I think some of the most discouraged patients we see are those who have had medical devices that fail. I’m very excited about the potential of UWEB to tackle some of the fundamental problems of implants.”

Ratner has spent the last 25 years at the UW studying the body’s interaction with synthetic materials for implants. Ratner jokes that he followed the career advice given to Dustin Hoffman’s character in The Graduate: “[Go into] plastics.” He studied polymer chemistry at Brooklyn Polytechnic Institute and in 1972 became one of the first postdoctoral students hired by Bioengineering Professor Alan Hoffman, who helped build the UW’s biomaterials program into one of the best in its field.

Ratner has done landmark research on the surface structure of biomaterials, demonstrating that the material surface controls the body’s reaction to implants. He believes recent advances in molecular biology and materials engineering bring the quest for new “healing” biomaterials into reach. Scientists have discovered specific receptors on cell surfaces that trigger the healing process. Meanwhile, engineers have developed techniques to design materials molecule by molecule that can mimic these cell receptors.

The UW, with its expertise in these areas and long tradition of interdisciplinary research, is uniquely suited to bring about a revolution in medical implant technology, Ratner says. UWEB brings together 26 UW faculty members from a dozen academic and medical disciplines. More than 30 industry partners—including health-care giants such as Johnson & Johnson, 3M and Dow Corning—also will take part in research, teaching initiatives, licensing of technology and student internships.

In addition to developing new medical implants, the UW will be training a new generation of engineers who know as much about biology as they do about engineering. Undergraduate and graduate students will be at the heart of the research and will become tomorrow’s leaders in the $50 billion-a-year medical implant industry, Ratner says. Special efforts will be made to attract women and ethnic minorities who are under-represented in science and engineering fields.

“To have the opportunity as an undergraduate to be involved with this research program involving so many people across so many disciplines is incredible,” says Joan Greve, a senior bioengineering student from Huntington Beach, Calif. “I’ve talked with undergraduates at other universities and they’re stuck doing a lot of library research. At the UW, and especially with UWEB, we’re able to do hands-on work in the laboratories—work that really matters for the outcome of the research.”

The UW biomaterials project has three research thrusts: new materials, cell biology and healing studies. Leading the healing team is Bioengineering Professor Joan Sanders, who received her doctorate in bioengineering from the UW in 1991. During the past six months, she has won awards given to outstanding young researchers by the Institute of Electrical and Electronic Engineers as well as the Whitaker Foundation.

Sanders’ first task in the biomaterials project is to study the mechanics of healing. When a wound occurs, the body automatically launches an inflammatory response to summon extra cells to the wound site, which is why it becomes red and puffy. Then, directed by highly specific protein signals, these cells begin dividing to regenerate tissue and close the wound.

The same inflammatory response occurs when a medical device is implanted in the body. But the cells summoned to the wound site don’t recognize the implant material. Instead of attaching to the device, the cells wall it off with scar tissue. This same reaction harmlessly occurs with bullets and pieces of shrapnel that can’t be removed from the bodies of some war veterans. But with many medical implants, like artificial heart valves and cochlear implants, the scar tissue disrupts the device’s performance and often requires another operation.

Sanders’ work has given her a clear understanding of a critical healing problem associated with medical implants that breach the skin, such as catheters. Since the skin doesn’t seal around the implant, the body’s main barrier against bacteria is broken and these implants almost always become infected. The implant must be removed and can’t be replaced until the infection is cleared up. Sometimes the patient isn’t able to wait that long.

In addition to studying the healing process, Sanders’ team will devise ways to test new biomaterials developed by UWEB. In collaboration with dermatology researchers, Sanders’ research group—which includes seven students, most of whom are undergraduates—already has figured out how to keep a small swatch of pig skin alive in the laboratory. This will allow researchers to test new biomaterials in living tissue.

“It’s a very controlled situation, but it’s a good first step,” Sanders says.

Tom Horbett, professor of bioengineering and chemical engineering, is an expert on how proteins and cells interact with foreign materials in the body. He will head up the project’s cell biology team. He has been working literally side-by-side with Ratner on medical implants for a quarter of a century. Horbett’s research group has two missions: to understand how cells and proteins communicate to prompt the body’s hostile reaction to foreign materials and then to figure out how to control those signals to induce normal healing.

Scientists know that proteins direct and carry out most cellular functions in the body, including healing. When doctors put a medical device in the body, for example, it is immediately covered with a layer of proteins that identify the implant as a foreigner. The proteins begin communicating with surrounding cells. These signals, Horbett explains, are believed to stimulate certain “problem cells,” which then form the tissue that encapsulates the implant.

Horbett’s team hopes to identify the proteins that “turn on” the encapsulation process so they can try to keep those proteins turned off. The group’s second major focus is to identify another set of key protein fragments, or peptides, that cells attach to in normal tissue. The plan is to coat implants with these peptides. Horbett wants to fool cells into thinking the implant is normal tissue so that they attach to the devices rather than build scar tissue around them.

“We’ll be pioneers when we get to that point,” Horbett says. “Other people have thought about using peptides to modify cell responses, but nobody has tried using peptides to prevent encapsulation.”

The materials-development effort is led by Bioengineering Professor Patrck Stayton, who is hailed as much for his educational outreach efforts with minority students as he is for cutting-edge research. He frequently invites students from historically black colleges to work in his laboratory.

Stayton’s background is in biochemistry, but he recognizes that new techniques in materials science and engineering hold the key to developing biomaterials that mimic body tissue. One promising new technique uses scanning probe microscopy or atomic force microscopy to analyze and manipulate materials at the molecular level. This allows engineers to control the shape, pattern and surface chemistry of individual molecules so they perform a desired function, Stayton says.

Another approach is to make molecules that automatically self-assemble into more complex structures. A common example of this is soap bubbles, which are made of lipids and hydrocarbons that, when put in water, naturally congregate and form simple, spherical membranes.

“In biology, we see that all of the molecules in the body know how to organize themselves into complex structures like tissue and organs,” Stayton says. “If we can build that self-assembly into our biomaterials molecules, they’ll grow themselves. We won’t have to worry about building a material molecule by molecule.”

As excited as Ratner and his fellow researchers are about what will happen in the laboratory, they know that UWEB’s greatest impact will be felt in the lives of patients who depend on medical implants.

Shortly after receiving her cochlear implant, Talbot-Lawson was walking through the UW Medical Center parking lot toward her car and heard an odd crickling noise. She looked around but couldn’t identify the source of the sound. Then she glanced down and noticed a small, dry leaf being pushed across the pavement by the wind.

“I never knew that leaves made a sound like that; I was amazed,” Talbot-Lawson says. “I don’t even want to think about losing my implant. The silence is too loud.”

Denice Denton: A new kind of dean

Denise Denton

When University of Washington President Richard L. McCormick set out to appoint a new dean of the College of Engineering, he wanted somebody who shared his progressive vision. He wanted somebody who had more than just a great research background. He wanted somebody who could champion diversity with the conviction of personal experience.

He wanted somebody who would be a new kind of dean.

With the appointment of Denice D. Denton—the first woman dean of engineering at a major U.S. research institution and, at 37, the youngest dean at the University of Washington—that’s exactly what McCormick got.

“One can make the argument that if you want to do things differently and you want to prepare for the next century, hiring a traditional individual from a traditional background may not get you where you want to go,” says Denton, formerly a professor of electrical and computer engineering and chemistry at the University of Wisconsin-Madison. “Over the next five years, all colleges of engineering will need to be more interdisciplinary in nature, more diverse with respect to student, staff and faculty populations and more agile in responding to opportunities.”

Being a woman isn’t the only thing that sets Denton apart. As co-director of the National Institute for Science Education, she has been a national leader in engineering education reform. She also is an expert in the development and use of extremely small-scale machining techniques for fabricating microelectromechanical systems, which are used, for example, to make air bags work.

The mathematical logic and the real-world application of engineering first piqued Denton’s interest as a teen-ager. She attended a summer engineering camp at Rice University in her hometown of Houston. A high school counselor who ignored traditional gender and career stereotypes encouraged Denton’s interest, and she went on to complete bachelor’s, master’s and doctoral degrees in electrical engineering at the Massachusetts Institute of Technology.

Continuing to encourage students, particularly women and students of color, to pursue engineering careers will be a priority for Denton. She envisions a strategic plan involving public schools, industry partners and alumni to increase the number of students and faculty from underrepresented populations in the College of Engineering.

“Enrollment projections for the so-called baby boom echo show a student population that is larger and more ethnically diverse than our current population,” Denton said. “The College of Engineering has a responsibility to prepare for that so we have the right people and programs in place to effectively serve a more diverse population. At the same time, we want to continue to offer the same high quality of education that we’ve been offering and to remain one of the most outstanding colleges of engineering in the country.”