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Distributed December 8, 2004
Contact Wendy Lawton

Fact Sheet
VA Limb-Loss Research: Bridging the Gap Between Man and Machine

Prosthetic limbs can be heavy, painful and awkward. Through a VA research program, Brown and MIT scientists and physicians are working to restore biological tissue and improve artificial limbs. Summaries of the research programs follow here, including limb lengthening, tissue engineering, osseointegration, robotics, neuroprosthetics and evaluation.
(Return to news release 04-061.)

Limb lengthening

Michael Ehrlich, M.D.
Vincent Zecchino Professor and chair, Department of Orthopaedics, Brown Medical School
Surgeon-in-chief, Department of Orthopaedics and Rehabilitation, Rhode Island Hospital, The Miriam Hospital

Roy Aaron, M.D.
Director, Center for Restorative and Regenerative Medicine, Providence VA Medical Center
Professor of orthopaedics, Brown Medical School
Attending physician, Rhode Island Hospital, The Miriam Hospital

When a patient loses a limb just below an elbow, knee, shoulder or hip, it is difficult to properly fit an artificial limb. If the existing limb is longer, the patient can use the joint and perform more activities while using less energy. To address this issue, the team will use a surgical procedure to lengthen bones in amputees in the hopes of improving the fit of a prosthesis and optimizing ease and range of movement.

The procedure, known as the Ilizarov method, involves stabilizing and elongating bone. During the procedure, a surgeon threads thin wires through skin and bone. These wires are then tethered to a metal frame outside the limb. By adjusting the wires, the bone stretches and new bone grows to fill the gap. Multiple adjustments, over many months, may be required to lengthen bone four or five inches.

Ehrlich has performed dozens of these surgeries, mainly in children and adults with birth defects such as dysplasia, or dwarfism. With amputees, 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. Taken together, the work will make longer, stronger bones that give amputees more freedom of movement.

Tissue engineering

Roy Aaron, M.D.
Director, Center for Restorative and Regenerative Medicine, Providence VA Medical Center
Professor of orthopaedics, Brown Medical School
Attending physician, Rhode Island Hospital, The Miriam Hospital

Deborah McK. Ciombor, Ph.D.
Associate director, Center for Restorative and Regenerative Medicine, Providence VA Medical Center
Assistant professor of orthopaedics, Brown Medical School
Co-director, Duffy Cell Biology Laboratory, Rhode Island Hospital

Michael Lysaght, Ph.D.
Professor of medical science and engineering, Department of Molecular Pharmacology, Physiology and Biotechnology and Division of Engineering, Brown University
Director, Center for Biomedical Engineering, Brown University

Edith Mathiowitz, Ph.D.
Professor of medical science and engineering, Department of Molecular Pharmacology, Physiology and Biotechnology and Division of Engineering, Brown University

Amputees may be left with a limb that contains damaged skin, muscle, cartilage or bone. An interdisciplinary research team will work to restore that tissue and its biological function.

The team’s first goal is to regenerate cartilage – dense, slippery, shock-absorbing material that cannot repair itself. The work involves recreating key signals in regenerating cells and the use of novel drug delivery – in this case, biodegradable polymer beads.

Work is already underway to encapsulate three kinds of human growth factors, hormone-like proteins critical to cell growth. The beads, which could be smaller than a pinhead, would be placed inside a joint along with precursor cartilage cells and supporting material such as collagen.

Inside the joint, the beads would slowly dissolve, releasing the proteins at the right time, in the right sequence. The team would also create the supporting material, or scaffolding, that protects growing cells. Ciombor said cartilage could be grown from a patient’s own cells and used either to repair or replace lost tissue.

Lysaght and Mathiowitz have already successfully encapsulated two of the three growth factors. 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. These cells would be placed in protective microcapsules and put into scaffolding or directly inside the joint.

If successful, these techniques would have a range of applications, including repairing – not replacing – damaged knee and hips.


Clyde Briant, Eng.Sc.D.
Professor and dean, Division of Engineering, Brown University

Jeffrey Morgan, Ph.D.
Associate professor of medical science
Department of Molecular Pharmacology, Physiology and Biotechnology, Brown University

Osseointegration is a process of connecting living tissue and titanium, a bond that provides a permanent, stable anchor for prosthetics. In recent years, osseointegration has been 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, a metals expert, is teaming with Morgan, a skin engineering specialist, to grow cells that will adhere to titanium, forming a natural seal around the bolts. “Skin doesn’t grow around any biomaterial we know of,” Morgan said. “Skin behaves as if these materials are a wound, so there isn’t any healing, leading to inflammation and infection.”

Briant will experiment with titanium and titanium alloys to find a combination that is strong yet porous enough for cells to adhere to. Morgan will alter human keratinocytes and fibroblasts – cells that make up both layers of the skin – to create cell types that will multiply and spread on metal as well as provide a strong bond. If the pair is successful, their technique could translate into improvements in other medical devices inserted into skin, such as catheters, ports and shunts.


Hugh Herr, Ph.D.
Assistant professor, Program in Media Arts and Sciences and
MIT-Harvard Division of Health Sciences and Technology
Massachusetts Institute of Technology
Director, Biomechatronics Group, MIT Media Laboratory

Herr’s research 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 cannot fuel it. Herr will build joints that can create the mechanical force needed to walk and climb without falls or fatigue.

To create proper knee rotation and propulsion, Herr will use special fluids that solidify into a paste when passed through a magnetic field, then reliquify when the energy is removed. Force will also be controlled by a tendon-like spring powered by an electric motor. The ankle system will either use a similar spring or an artificial muscle, made of electroactive polymers (EAPs), which turn electrical energy into mechanical work.

To control these joints, Herr will use the BIONTM, a wireless microchip about the size of a grain of rice, developed by the Alfred Mann Foundation. The chips will be injected into existing leg muscle, where they pick up signals from nerves and send movement instructions to the knee and ankle. Additional sensors, attached to the heel and forefoot of an external prosthesis, will relay information about ground reaction forces to a microprocessor to further guide movement of the artificial joints.


John Donoghue, Ph.D.
Henry Merritt Wriston Professor and chair, Department of Neuroscience, Brown University
Director, Brain Science Program, Brown University

Work by Donoghue and his colleagues has led to a system that records brain signals, decodes them, and transforms them into movement commands that can control a computer cursor.

The system, called BrainGate, is currently being tested in a quadriplegic by Cyberkinetics Neurotechnology Systems Inc. Preliminary results show that the 25-year-old patient can switch on lights, change television channels and open e-mail using only his mind. The promise of 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, who led the original Brown research and went on to co-found Cyberkinetics, said three challenges must be met before BrainGate can be used to operate robotic limbs. First, the system must get smaller. In the current version, brain signals travel from a sensor implanted in the motor cortex out through a pedestal on the skull, then travel by wire through two sets of neural processors. Donoghue will work with Arto Nurmikko, an engineering professor at Brown, to create a system that instead would feed brain signals from the sensor through a hair-thin fiber optic cable to a processor about the size of a cardiac pacemaker, implanted in the chest. This would internalize the system, eliminating the need for wires or bulky equipment.

In the new system, communication between mind and machine would also be two-way. Sensory information from the robotic limb would be relayed to the brain to stimulate the cortex and further guide movement. The Brown team would create this new stimulator system, making it compatible with the existing BrainGate sensor.

Finally, Donoghue will work with Michael Black in Brown’s Computer Science Department to improve the neural decoding device so it can create control signals for complex motor tasks, such as grasping. The decoder will work in real-time and be fully automated.

Measuring Success

Linda Resnik, Ph.D.
Assistant professor, Department of Community Health, Brown Medical School

Vincent Mor, Ph.D.
Professor and chair, Department of Community Health, Brown Medical School

There are many tools, such as patient surveys and physical performance tests, which measure progress as amputees go through rehabilitation. But there is not 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. Resnik, working with Mor, will conduct a study to compare existing tools. This study, which will begin in early 2005, will recruit more than 200 amputees from military hospitals as well as VA facilities.

Results will help the research team choose outcome measures that will be used in human clinical trials under the VA research program. Limb lengthening will likely be the first procedure tested in humans.


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