"The Machinery of Life," Feature Article, February 2004

FEATURE FOCUS: Biotechnology -- MEs and MDs

the machinery
of life

Between physics and biology lies a rift in language that doctors and engineers must cross before they heal the sick.

by Paul Sharke,
Associate Editor

A 13-year-old girl from Wimbledon and another, 10 years old, from Tooting are among an exclusive group of young bone cancer patients in England who will be skipping painful leg lengthening procedures these next few years because of a new device dubbed the "bionic bone." Victims of rare osteosarcoma, the girls would have had to undergo at least several surgical adjustments to their prosthetic implants to keep their affected legs growing at the same rate as their healthy limbs.

But a motor, a gear, and a dose of ingenuity have changed that. Now, a short office procedure adds 4 mm of painless incremental growth to the child's leg. The procedure can be repeated as often as possible to keep up with the child's development.

A patient undergoes leg lengthening without surgery. An external field assembly propels a tiny implanted rotor at 3,000 rpm to drive a gear reducer.

In the past, doctors had to lengthen the prosthetic with a key inserted surgically into the patient's leg—a costly procedure often followed by days of tearful post-op recovery. Now, after 15 minutes with her leg in a tunnel, a patient stands up from the table and walks away.

A joint effort of bioengineers at the University College London Center for Bioengineering and orthopedic surgeons at the Royal National Orthopaedic Hospital in Stanmore, the device—formally called an extendable prosthesis—was 11 years in the making.

According to Jay Meswania, technical manager of Stanmore Implants Worldwide Ltd. and a research fellow at University College London, the prosthesis translates the 3,000-rpm rotation of an implanted rare earth rotor through a 13,061:1 gear ratio to move a lead screw a quarter millimeter every minute.

The field, known officially as limb salvage, has begun helping young bone cancer patients whose prognosis, only a decade ago, would have been amputation. Because prosthetic surgery requires removing the so-called growth segment from a patient's bone, the procedure invariably stunts further development in an affected leg, leaving skeletally immature patients with mismatched limbs.

Wright Medical Technology Inc. of Arlington, Tenn., takes a different approach to solving the same problem. Its Repiphysis system, cleared by the Food and Drug Administration in 2002, implants a spring-loaded femoral or tibial extension. A heat-sensitive polymer encases the spring within a pair of nested tubes. An external collar provides a source of electromagnetic waves for softening the polymer. Under controlled pulses of energy applied from outside the child's body, the spring expands slowly in the softened material, stretching her limb.

These noninvasive expandable prostheses are third-generation devices that began developing in the late 1970s and early 1980s in Britain and the United States. The first extendable prosthetics used screws for lengthening. Later came modular designs in which a removable portion could be exchanged with a longer section as the patient grew. Both styles could be extended only through surgery.

The Wright prosthesis—invented by French engineer Arnaud Soubeiran—and the Stanmore design both embody machines that literally stand in for living tissue gone bad. They practically duplicate growing cells.

ME in the OR

Brian McDaniel, a mechanical engineer who manages Wright's custom orthopedics department, said that the new wave of noninvasive, extendable prosthetics was solving a "big problem" in the limb salvage community. Although a majority of the 200 or so orthopedic oncology specialists practicing in the United States are still using traditional modular prostheses, McDaniel said that many of them are giving the noninvasive forms strong consideration because they limit the surgery and rehabilitation their young patients must endure.

Rehab was a big portion of the multiple-surgeries approach to limb lengthening because doctors would ordinarily try to get as much done as possible while the patient was under sedation. Limited mainly by how much the nerves could stretch, a surgeon might add several centimeters to a leg at once, anticipating that the healthy leg would catch up.

A Repiphysis system document for surgeons cautions that pre-growing is unnecessary and undesirable with the Wright system. Fitted with a Repiphysis prosthetic, a six-year-old might sit through 12 expansions over the course of his treatment, adding, perhaps, 6 cm in that time. By more closely approximating the body's own growth pattern, the system produces smaller incremental growth with fewer limitations on limb movement.

Sometimes, a child might have to be fitted with two implants over the course of a treatment, McDaniel explained. The amount the device can grow is limited by how much bone is removed. The more bone that is taken out, the more the prosthesis can extend.

The Repiphysis lineup of implantable, growing prostheses relies on the release of spring energy within a softening polymer for adding length to a child's limb.

Each device is custom designed and built, he said, generally starting about six weeks before the child's operation. That's not much lead time, but it often takes a month and a half from the original diagnosis for the doctor to gauge the child's response to chemotherapy. The engineering and manufacturing departments can gear up to produce a prosthesis even faster under extraordinary circumstances.

"We haven't missed an operation yet," McDaniel said. When you are saving young lives, no one frets much over working weekends, he added.

That same attitude goes for the doctors.

McDaniel spends a lot of time with doctors and, as a group, finds orthopedic oncologists to be especially compassionate. It's a very small group and hence a well-defined market. By comparison, regular orthopedists—the kind who implant hips and knees in adults—number 10,000 or more in the U.S. alone.

Generally, surgeons welcome the presence of a mechanical engineer in the operating rooms, he said. And there, the mechanical engineer, for whom an orthopedic surgical theater resembles a well-equipped carpentry shop, feels right at home.

No Live Demos

McDaniel has no problem handling hammer and saw. In fact, one of his jobs involves assisting the Wright sales force with "sawbones demos" in which he demonstrates the implant procedure on foam bones. He has no problem with the language of biology, anatomy, or physiology, either. He started college in pre-med before switching to engineering.

When he first began working, McDaniel spent a lot of time learning medical terms and ideas. Today, he's more apt to be educating doctors in the language of engineering.

McDaniel's associate on the Wright team, Robert Daily, has been with the company for 14 years. Unlike McDaniel, whose interest leaned toward medicine from the start, Daily's path to his present position followed a more traditional mechanical engineer's route. After a stint in the Navy's nuclear power program, Daily worked for tire maker Michelin before coming to Wright as a manufacturing engineer.

"As in any industry, you're expected to learn the lingo," Daily said of working with surgeons, adding that the doctors "don't give our way a bit."

Daily interacts mostly with the physicians, not the patients, and called MDs his true customers. The adage that the customer is always right may apply here even more than usual.

"Doctors like to be in control," Daily explained, and that attitude sometimes extends past their operating rooms. More than a few orthopedists studied undergraduate engineering before medicine, and that little bit of knowledge can sometimes hinder discussions about certain designs that are impractical to make.

This is a closeup of a femoral extension, each of which is a custom design.

The work is exceptionally rewarding, Daily said, as one would expect of a business that helps children keep their limbs. From an engineering perspective, Daily enjoys the brisk pace of the Repiphysis custom projects and the nearly immediate gratification that making them gives.

"The process is very rapid and very real," he said. Compared to the nine months or so that accompany a typical new implant development, working with Repiphysis implants never leaves him feeling "stuck in mud," he said.

Meswania, from Stanmore Implants, said he often tones down some of the engineering talk when discussing various implants with surgeons. But when it came time to make the bionic bone work, engineering was never far from his mind.

Meswania spent about two years in operating rooms measuring the force required to stretch muscle and tissue in patients with invasive implants. Normally, it took about 1,500 newtons to stretch a leg by 9 to 10 mm, he said. That was tremendous force to produce in a mechanism that had to fit within the diameter of the prosthetic tube. But more lengthenings of shorter reach—a decided advantage of the noninvasive design—meant that a lower force could be used. Even with this advantage, however, the first bionic bone couldn't exert sufficient force without deforming the gears. It was never implanted.

Pressing forward, Meswania contacted Davall Gears of Hatfield, England, for help in improving the efficiency of the diminutive gearbox. The company recommended a number of changes, not the least of which was a new manufacturing technique that produced extremely fine-tooth mesh down to a module (the ratio of pitch diameter to number of teeth) of 0.1.

The company explored other ideas as well, Meswania said, including finding a substitute for the soft, implantable grade stainless steel that orthopedists customarily use despite its resistance to hardening. Through a combination of material, hardening, and manufacturing, Davall produced a high-reduction, two-stage gearbox that could transmit the torque necessary to stretch tissue.

A small-diameter rotor drives the gearing. Actuated across a huge air gap and a flesh-and-blood divide, the tiny rotor synchronized surprisingly well with an external stator supplied by ABB, Meswania said. The field strength remained consistent over the length of the stator as well. Flexibility in the system means that a patient need not be immobilized during a lengthening.

The rotor uses two niobium-iron-boron magnets mounted to a 12 mm diameter disc. The stator, sized to fit over a child's leg, measures 180 mm across its interior surface.

EMR Silverthorn of Wembley, England, supplied the ABB stator cores, wired according to the requirements of Stanmore Implants. According to EMR, the stator cores are series wound in two poles on a standard 180-frame size. Tests showed that 552 turns of 1.06 mm wire, star connected, produced the best results.

Hard Science Meets Soft Tissue

It's no challenge finding a link between orthopedic medicine and mechanical engineering. The joints, the stress, the motion—engineers move readily within these realms. Years of partnerships between mechanical engineers and orthopedists have firmly cemented the relationship.

But moving from the idea of implanting artificial materials to the concept of engineering actual living systems requires a bigger imaginative stretch. It's in the application of engineering principles to medical problems and biological systems that the new Department of Bioengineering at Stanford University will be spending its time.

Distinct from the Stanford degrees in biomechanical engineering, the M.S. and Ph.D. programs in bioengineering will combine courses in biology, engineering, and medicine in such areas as regenerative medicine, tissue engineering, biomedical computation, cellular and molecular systems, and quantitative biology.

Biomechanical engineering attracts students interested in applying the traditional elements of mechanical engineering—dynamics, continuum mechanics, multiscale computational mechanics, and design—to research questions in medicine or biology.

Noninvasive lengthening of the Repiphysis prosthesis uses an external collar to soften an implanted polymer with electromagnetic energy.

The master's degree in bioengineering, which will draw students from many undergraduate disciplines, includes a two-quarter course in medical device innovation, said Scott Delp, chairman of the jointly managed bioengineering department. Because engineers excel at problem solving and not necessarily the memorization required to learn new languages, students in the course will be assigned specific design challenges in areas such as cardiology, orthopedics, or neurology.

Motivated to learn the language that's needed to understand and resolve his specific problem, a student will learn to express himself along a narrowly focused beam, Delp explained. Students will then review the projects of their peers to add breadth to their medical vocabularies. At the end of two semesters, students are expected to be conversant with physicians and other members of the medical community, he added.

Biology hasn't long been the quantitative science that physics has been. It's been populated by many, many observations and fewer theories. But with the emergence of overwhelming data from genomics, the need for mathematical and computational tools becomes more important for success in the biological fields.

Delp predicts a day when a course in biology will be taught in all undergraduate engineering programs. It offers a key to understanding what Delp labeled "big-picture problems."

Michael Neel, an adjunct faculty member at St. Jude Children's Research Hospital in Memphis, Tenn., spent an extra year beyond his residency becoming an orthopedic oncologist. He has implanted about 20 Repiphysis prostheses since 1999.

He's just now deciding what to do for several of his patients who've ended their childhood growth. The question is whether to replace the extendable prosthetics now or at the first instance of loosening or failure, Neel said. The growing prostheses aren't intended to last through adulthood, he explained.

The need to build the devices both strong, to support the increasing weight of growing children, and light, so a child has the semblance of normal limb movement, presents a classic problem that any engineer can recognize. Add to that the problem of fixing hard metal to softer bone, and the need for engineering analysis quickly becomes evident.

Neel, who has established a close relationship with the people at Wright, relies on engineers there to assess the soundness of various limb salvage solutions proposed for his patients. And the Wright people rely on Neel and others of his kind to provide anatomical understanding and patient data for developing devices that fit and behave like the real thing.

Bioengineering, it turns out, is not an us-versus-them proposition at all. Doctors and engineers are on the same team. Yes, there are concepts and terms to learn that are completely unfamiliar to undergraduate ME students. But anyone who can master physics can learn biology, Delp said. All it takes is a willingness to immerse oneself in the language of life.