Research group exploring limb loss hopes biohybrid will bridge gap between human and machine

Scientists based at Brown and MIT receive $7.2 million from the Department of Veterans Affairs.

by Wendy Y. Lawton

Thanks to better body armor and improvements in front-line medical care, more soldiers survive combat injuries sustained in Iraq than in any other war in U.S. history.

But according to a government report, more surviving soldiers are losing arms and legs. Historically, 3 percent of soldiers wounded in action required some amputation, but that rate has jumped to 6 percent in Iraq.

Now, through $7.2 million from the Department of Veterans Affairs, a team of researchers is working to restore natural movement to amputees - particularly Iraq veterans. Within five years, scientists based at Brown and the Massachusetts Institute of Technology hope to have created "biohybrid" limbs that will use regenerated tissue, lengthened bone, titanium prosthetics and implantable sensors that allow an amputee to use nerves and brain signals to move an arm or leg.

Roy Aaron (left), a professor of orthopedics at the Medical School and an attending physician at Rhode Island Hospital and The Miriam Hospital, will serve as director of the new Center for Restorative and Regenerative Medicine created by the Providence V.A. Medical Center. He also will oversee the Brown and MIT investigators. All have research appointments at the Providence V.A.

Aaron said the aim of the work through the center is to give amputees better mobility and control of their limbs and reduce the discomfort and infections common with current prosthetics.

There are more than 1.2 million Americans living with limb loss due to trauma, infection or disease, according to the Amputee Coalition of America. Aaron said the work through the V.A. could help many of them. But Aaron feels a special responsibility to soldiers.

"We need to make medical care a priority for these troops blown apart in this war," he said. "Soldiers want to come home and do the things they used to do. Some even want to go back into the service. As a society, we should try and help them return to their lives."

The team is multidisciplinary, with expertise in orthopedic surgery, physical rehabilitation, community health, tissue engineering, neuroscience, artificial intelligence, robotics and materials science.

Their research also will bridge the gap between human and machine. Aaron said biohybrid limbs will meld human tissue with man-made materials, such as titanium bolts or robotic knees or ankles. A prosthesis could even be controlled by an amputee's own muscles and brain signals, using microchips and implantable sensors.

"Advances in tissue engineering, robotics and neuroscience put many of our goals within reach," Aaron said. "While many of the tools and techniques we're using are being tested across the country, this project marks the first time they will be pulled together to improve care for amputees, particularly veterans."

The project - like many in science - started with a little money, some luck and a big idea.

The money came by way of a $93,920 "seed" grant from the Office of the Vice President for Research. Aaron and faculty members Michael Lysaght, Deborah McK. Ciombor and Edith Mathiowitz received the grant last year to conduct tissue engineering research.

Luck arrived when Aaron learned that Mindy Aisen, the V.A.'s director of rehabilitation research and development, was eager to work with John Donoghue, chair of the Department of Neuroscience, and Hugh Herr, an MIT robotics expert.

The big idea came together slowly as Aaron looked at the expertise at Brown, considered the outside interest, and began to connect the dots. "We've got tissue engineering, neurotechnology, materials science, surgery," he said. "All of this work could come together in a biohybrid limb."

Had it not been for a ruptured disc, however, Aaron never would have submitted his idea to the V.A. The injury forced him to lie flat on his back for a month. So he "wrote" the proposal by talking into a Dictaphone. A staff member typed up his plan.

"My dream with this project is to allow someone who has lost an arm to brush their teeth or use a computer, or to allow someone who's lost a leg to climb stairs or ski again," Aaron said. "I think we have the technology. We just need the courage to try it out."

The limb loss research teams and their work

Work through the Providence V.A. Medical Center falls into six research programs. The rundown:

Limb lengthening

The team: Roy Aaron and Michael Ehrlich, Vincent Zecchino Professor and chairman of Department of Orthopedics and Surgeon-in-Chief, Department of Orthopaedics and Rehabilitation, Rhode Island Hospital, The Miriam Hospital

The work: Use a surgical procedure, mainly performed to correct birth defects, to lengthen bones in amputees in the hope of improving the fit of a prosthesis and optimizing ease and range of movement. The goal is to allow use of joints, which are critical for eating, climbing and other activities. Ehrlich and Aaron will also conduct basic cellular research aimed at speeding bone healing after surgery.

Tissue engineering

The team: Roy Aaron; Deborah McK. Ciombor, assistant professor of orthopedics, Brown Medical School and co-director, Duffy Cell Biology Laboratory, Rhode Island Hospital; Michael Lysaght, professor of medical science and engineering, Department of Molecular Pharmacology, Physiology and Biotechnology and Division of Engineering, and director, Center for Biomedical Engineering; Edith Mathiowitz, professor of medical science and engineering, Department of Molecular Pharmacology, Physiology and Biotechnology and Division of Engineering

The work: Restore damaged tissue and its biological function. The team's first goal is to regenerate cartilage. Scientists will encapsulate time-release growth factors to inject into damaged joints along with precursor cartilage cells and supporting material such as collagen. Researchers hope that this drug delivery system, coupled with the polymer scaffolds, could also be applied to bone. Researchers will explore a different technique, which involves genetically modifying living cells so that they make and release growth factors. If successful, these techniques would have a range of applications, including repairing - not replacing - damaged knee and hips.

Osseointegration

The team: Clyde Briant, professor and dean, Division of Engineering; Jeffrey Morgan, associate professor of medical science, Department of Molecular Pharmacology, Physiology and Biotechnology

The work: Osseointegration is a process of connecting living tissue and titanium, a bond that provides a permanent, stable anchor for prosthetics. In recent years, osseointegration is used to attach titanium bolts to bone in the existing limb of an amputee. Prosthetic limbs can then be attached to the bolt, which protrudes from the skin. One complication, however, is infection. Briant and Morgan will try to grow cells that will adhere to titanium, forming a natural seal around the bolts. If successful, the technique could translate into improvements in other medical devices inserted into skin, such as catheters, ports and shunts.

Robotics

The team: Hugh Herr, assistant professor, Program in Media Arts and Sciences, MIT; assistant professor, MIT-Harvard Division of Health Sciences and Technology; director, Biomechatronics Group, MIT Media Laboratory

The work: Herr will focus on creating active knees and ankles controlled by an amputee's own nervous system and powered by muscle-like devices. The aim: Make artificial legs perform like biological ones. Currently, prosthetic knees and ankles can stop movement but can't fuel it. Herr will build joints that can create the mechanical force needed to walk and climb without falls or fatigue. To control these joints, Herr will use a wireless microchip with the trademarked name BION. It will be injected into existing leg muscle, where it will pick up signals from nerves and send movement instructions to the knee and ankle.

Neuroprosthetics

The team: John Donoghue, Henry Merritt Wriston Professor and chair, Department of Neuroscience, and director, Brain Science Program; Arto Nurmikko, L. Herbert Ballou University Professor of Engineering and Physics, Division of Engineering; Michael Black, professor, Department of Computer Science

The work: Donoghue will use a system currently in clinical trial to record brain signals, decode them, and transform them into movement commands that can control a computer cursor. The promise of the system, called BrainGate, is not only to allow paralyzed people to control their environment through a computer, but to allow them to control their own prosthetic arms or legs. Donoghue will work with Nurmikko to miniaturize the system and create a new companion system that will relay sensory information from the robotic limb to the brain and further guide movement. Donoghue will work with Black to improve BrainGate's decoding device so it can create control signals for complex motor tasks, such as grasping.

Measuring outcomes

The team: Linda Resnik, assistant professor, Department of Community Health; Vincent Mor, professor and chair, Department of Community Health

The work: There are many tools, such as patient surveys and physical performance tests, which measure progress as amputees go through rehabilitation. But there isn't a lot of research that shows which tools are the best measures of outcomes such as quality of life, mobility and satisfaction with the prosthetic limb. The team will conduct a study to compare existing tools. This study, which begins in early 2005, will recruit more than 200 amputees from military hospitals as well as Veteran's Affairs facilities. Results will help them choose outcome measures that will be used in human clinical trials under the V.A. research program. Limb lengthening will likely be the first procedure tested in humans.