Replacement Parts

by Michael Cohen

Christopher Lambert, right, and graduate student Eugene Douglass are exploring ways to reconnect severed neurons using fine gold wires.

A multidisciplinary team works to meet the complex challenges involved in integrating advanced prosthetic devices with the body and the brain.

Thanks to advances in military technology and battlefield medicine, many soldiers who would have died from their injuries in wars past now survive. The result is a lower combat fatality rate but a dramatic increase in the number of men and women who return with severe injuries—including missing arms and legs. Their best hope for a reasonable recovery rests on the development of a new generation of prosthetic devices with significantly enhanced capabilities. At WPI, a multidisciplinary research team is attacking some of the most complex problems that stand in the way of that goal.

"We're taking a comprehensive approach to this research, looking to leverage our expertise to fill the gaps and advance the field," says W. Grant McGimpsey, professor of chemistry and biochemistry and director of the WPI Bioengineering Institute (BEI). "Our program has components we hope will have an immediate impact on existing prosthetic technology, and others that will address fundamental questions we need to answer before advanced neuroprosthetics can be controlled by the nervous system and fully integrated with bone and tissue."

Much of this research is being conducted through the BEI Center for Neuroprosthetics, which recently embarked on a twoyear project funded by the Military Amputee Research Program of the U.S. Army’s Telemedicine and Advanced Technology Research Center (TATRC). The grant will cover three areas of prosthetics research: control-signal processing, nervous system integration, and tissue interface.

Degrees of Freedom

National Leadership

Recognizing WPI's leading work on neuroprosthetics, the John Adams Innovation Institute of the Massachusetts Technology Collaborative awarded the university a $150,000 grant to support the growth of the BEI Center for Neuroprosthetics. With a portion of the funds, WPI will sponsor a national conference in 2009 that will bring together experts to share insights and discuss the challenges they face.

Neurons grow on an artificial surface in Stephen Lambert’s lab. Axons can be seen extending along channels etched in the material.

Through the TATRC grant, Clancy's lab will study muscle signals in the forearms of healthy subjects. Using a specialized device with an array of 128 electrodes, Clancy will measure and analyze the signals propagating along the muscles, while another apparatus records the movement and forces of the subject's wrist and fingers. "We hope to isolate several independent control signals, at different locations along the arm," he says.

If this work is successful, understanding the dynamics of those isolated control signals may allow existing motorized prosthetic arms and hands to achieve multiple degrees of freedom. Since there is a close relationship between muscle signals and nerve signals, Clancy hopes this work will yield data that is applicable to the more complicated task of directly linking mechanized prosthetics with a person’s nervous system.

Man-Machine Interface

Current prosthetic limbs rely on remnant musculature for control, but in many cases there isn't enough muscle remaining, or what there is cannot control the device. A better solution would be to link the artificial limbs directly to the nervous system. “We want to build a man-machine interface connecting the device with the brain, so if a person wants to move her arm, she thinks it and it happens,” says Stephen Lambert, research affiliated professor, who is leading the neural connection portion of the TATRC program.

"We want to build a man-machine interface connecting the device with the brain, so if a person wants to move her arm, she thinks it and it happens."

Lambert's team will try to direct the growth of neurons on an artificial surface, such as glass, gold, or silicone, so their axons (the long, thin fibers that carry electrical impulses) extend along channels etched in the materials. The team will try to achieve predictable neuron growth and axon myelination (fully developed axons are covered with a sheath of myelin, a substance that insulates them, much like the plastic coating that insulates electrical wires). "This is very basic research, looking particularly at what factors and substrates are important for the growth of neurons," Lambert says. "Connecting to the nervous system is a complicated problem; we are very much in the infancy of this effort."

Watch a video about WPI's research in regenerative biology.

Human limbs can move in multiple planes-engineers say they have multiple degrees of freedom. Electrical and computer engineering professor Ted Clancy is working to isolate the signals that propagate through muscles, hoping to use them to create control mechanisms that will permit prostheses to move more like natural limbs.

Using Nature as a Model

In related research, Christopher Lambert, BEI research associate professor, is working on a novel way of linking distant neurons using thin gold wires with engineered surfaces. The technique could be used to reconnect parts of nerves severed by trauma. The research is being carried out in collaboration with Anne Rittenhouse, associate professor of physiology at the University of Massachusetts Medical School. "If we can make it work, it would be important for neuroprosthetics," Lambert says, "especially when you need to cover a long distance to connect the device with healthy neurons."

"There has to be a healthy, co-hesive tissue interface with the implant, or it will fail. We will study the problems associated with that interface."

Healthy Connections

Whether controlled by the nervous system or remnant muscle activity, the advanced prosthetics that WPI researchers envision will need a permanent connection to the body, with a fixed metal or composite post anchored in bone and multiple layers of tissue forming a seal around it. Posts are routinely implanted in bone as part of knee and hip replacement surgery, but connecting a post to an external device presents unique challenges. "There has to be a healthy, cohesive tissue interface with the implant, or it will fail," says George Pins, associate professor of biomedical engineering. "It's important for the skin around the post to be able to move substantially. We will study the science and engineering problems associated with that interface."

Infection is one of the biggest risks of having a post extrude through the skin. Should excessive scar tissue form around the post, it could render the connection to the prosthesis painful, if not unworkable. Through the TATRC program, the WPI team will study the tissue interface at two levels. In his lab, Pins will focus on the epidermis (the top layer of skin) and study how skin cells interact with various post materials. Kristen Billiar, associate professor of biomedical engineering, will examine the deeper layer of skin tissue, the dermis, and attempt to coax dermal cells to create a rigid bond around the post. This would provide a foundation for the epidermis, which could then form a tight but flexible seal around the post to help prevent infection.

"Through this research, we may gain new knowledge and develop new devices that will have applications beyond prosthetics, helping improve life for victims of stroke, for example, or helping cure neurodegenerative diseases."

Additional Readings

Nano- and microtechnologies for the development of engineered skin substitutes
Pins, G., and K. Bush (graduate student), in Micro- and Nanoengineering of the Cell Microenvironment: Technologies and Applications (Artech House, 2008).

Biomechanical and biochemical characteristics of a human fibroblast-produced and remodeled matrix
Ahlfors, J. E. W., and K. L. Billiar, Biomaterials, vol. 28, no. 13, pp. 2183-2191, 2007.

To create a model system, Billiar will grow human skin cells in a gel of fibrin, the protein that helps blood clot at the site of an injury. The tissue will grow in small cylinders, with small posts set in the middle. Mechanical devices will stretch the tissue in different directions, with increasing force, as Billiar’s team watches to see how strong the tissue becomes and at which point it tears or separates from the posts. They will also observe how the stretching and stressing changes the skin cells and the extracellular matrix (the connective tissue between cells). “We know these forces will have an impact,” Billiar says. “But can we understand it well enough to direct the cells to change in ways that make for a more stable environment for the implant?” In related research, Marsha Rolle, assistant professor of biomedical engineering, uses genetic tools to manipulate mesenchymal stem cells, which come from human bone marrow. Rolle is trying to prompt the cells to differentiate into specific kinds of tissues, like blood vessels, and to pump out proteins that are important for extracellular matrix development during wound healing. “If we can get these stem cells to self-assemble into their own three-dimensional architecture,” she says, “it could help with the healing around the site of the implanted prosthesis.” Collectively, the ongoing research into next-generation prosthetics at WPI highlights the growing intersection of biology and engineering. “We have an obligation to do everything we can to help these soldiers achieve a better quality of life,” says BEI director McGimpsey. “And through this research, we may gain new knowledge and develop new devices that will have applications beyond prosthetics, helping improve life for victims of stroke, for example, or helping cure neurodegenerative diseases.”

Marsha Rolle, left, and graduate student Tracy Gwyther are exploring novel approaches to tissue engineering and tissue regeneration, including techniques aimed at coaxing cells to form new functional blood vessels (see insert). Rolle is also working with mesenchymal stem cells, hoping to promote the healing of tissue around implants by encouraging the cells to self-assemble into three-dimensional tissue architectures.