By Robert Emro

Seen through an engineer’s eyes, the human body is an incredible machine made of muscle and bone—animated by that mysterious thing called soul or consciousness to be sure—but subject to exactly the same physical laws as a bridge, a motor, or a microchip.

For 30 years, the Cornell–Hospital for Special Surgery Program in Biomechanical Engineering has brought engineers and surgeons together to unravel the secrets of this complex contraption. Their work has helped hundreds of thousands of patients, and the promise of more improvements lies just over the horizon.

Don Bartel University Photo

Bartel had been working with the researchers at HSS, the orthopedic affiliate of what is now Weill Cornell Medical College, since the early 1970s. "I’ve always worked within a clinical setting and I think I’m just built that way," says Bartel, the Willis H. Carrier Professor Emeritus in the Sibley School of Mechanical and Aerospace Engineering. "I like working on things that make a difference in the short term. I guess it was natural I would seek out the others."

The partnership really flourished after HSS hired Albert Burstein, now famous as a co-developer of the Insall-Burstein knee implant, to set up its biomechanics department. "The whole idea was, we had a group of engineers that would be in a vacuum without a connection to an engineering school and at Cornell, there was a group getting into biomechanics that would have the ability to access a rich clinical and biomedical research environment down here," says current HSS Department of Biomechanics Director Timothy Wright, who was hired as a postdoc the same year the program was established. "And it’s been an incredibly productive collaboration."

Dr. Timothy Wright Provided

Uncontrollable Accounting

Working with Burstein and now Wright, Bartel’s expertise in design optimization and numerical stress analysis continues to make him instrumental in the development of artificial joints. When natural joints wear out, replacements are either fixed to the bone with an acrylic or made with a porous metallic layer into which the bone can grow. Either way, the replacement must be able to withstand loads that can reach several times body weight during daily activities—ideally for the rest of the patient’s life.

In designing joint replacements, certain variables can be controlled, like the shape of components, the materials used, and the desired surgical placement. But environmental variables that affect the performance of the device—like patient weight, bone properties, and small variations in actual placement—are beyond control. Bartel uses sophisticated statistical methods to estimate their effects.

The goal is to design a joint that can perform in the real, unpredictable world. "By using these statistics-based methods, you can now account for the variability that affects the system from patient to patient and in the same patient over time with disease and age," Bartel says. "By determining their relative influence, you can determine where you can get the most bang for the buck in improving the system."

Thirty years ago, "revision" of total knee and hip replacements was often necessary after just five to 10 years. Today, these are some of the most successful operations by any measure, says Bartel, with replacements lasting 20 years or more in 95 percent of patients. And that’s due in large part to putting engineers in a hospital setting. "The patient was never far from view and we were there to improve patient care," he says. "The only way you can do that is working directly with surgeons who know what the problems are."

Now retired from Cornell, Bartel continues to work on improving joint design at HSS, where he is a senior scientist. "It’s been a great 30 years to work on implants," Bartel says. "I kind of got in on the ground floor. Nowadays, with biology, there’s more to learn about the system and the research is longer term."

The evolution of biomechanics

Marjolein van der Meulen University Photo

Unlike man-made materials, human tissues are not static. They respond to a variety of environmental factors. Researchers have long known, for instance, that bone mass will increase in response to loading—a classic study in 1970 showed that the bone mass of tennis players was greater in their dominant arm. That’s why Bartel designs joints that transfer their loads to the surrounding bone. If they didn’t, the body would remove the unused tissue and the bone would weaken. It’s also why women with osteoporosis are advised to exercise. But little research has been done to understand exactly how bone remodels itself. That information could aid in the development of drugs to treat osteoporosis.

"Bone is a very adaptive material but most people don’t think of it that way," van der Meulen says. "I’m interested in understanding the adaptation process and also taking advantage of that process to some extent to form bone."

Working with Wright and Mathias Bostrom, an orthopedic surgeon at HSS, van der Meulen studies adaptation in animal models, varying the length, magnitude, frequency, and number of loading cycles to better understand the process. "There’s a perception that magnitude of the forces is more important than other parameters, but we don’t fully know that," she says. "We’re trying to tease out and elucidate which parameters are the relevant ones."

Aging and estrogen play a large role in changes in bone mass—bone loss spikes after menopause—and van der Meulen’s group is also studying their effects on the tissue found at the ends of bones, called cancellous bone. "It’s a challenge because there’s a lot less of it, and there are fewer models for loading of cancellous sites," she says. "We’re working on developing models for these clinically relevant locations. Half of all fractures in women with osteoporosis are in the hip, wrist, or spine—locations that are predominantly cancellous tissue."

Besides benefitting patients with osteoporosis, a better understanding of bone adaptation could lead to improvements in fracture healing. With Bostrom and others at HSS, van der Meulen is working to understand how forces applied to fractured bones can both enhance and inhibit healing. The team is focusing on the interaction between loading and biology, which come into play when surgeons use metal plates to immobilize broken bones. "The healing response is different when you put a plate over the bone," van der Meulen explains. "You bring the ends in close proximity and it heals well and more quickly, but in the long term, you start to lose bone under the plate because it’s shielding the bone from the load."

Preclinical studies using mice indicate that cancellous bone mass loss can be prevented by mechanical loading, possibly offering a nonpharmacological treatment to prevent rapid onset osteopenia and associated fractures. The figure at right shows the midtibial plateau of paired tibias from 16-week-old mice. Experimental mice had surgery to remove the sex organs (ORX), which results in rapid loss of cancellous bone mass; control mice had simulated surgery to control for surgical effects (Sham). Forces were applied to the left tibias of both groups for six weeks. Comparison to the control (non-loaded) tibias showed that cyclic mechanical loading prevented bone loss that occurs as a result of withdrawal of the male sex hormones but altered the architecture of the cancellous bone. Reproduced from J Bone Miner Res 2008;23:663-671 with permission of the American Society for Bone and Mineral Research

But just as the strength of a bridge is not only determined by the size of its beams and their configuration, there is a third factor to consider: the quality of the materials. The unexpected effects of some osteoporosis drugs are more likely due to different tissue properties and distributions, says van der Meulen. To find out how material properties contribute to osteoporotic fractures, she has teamed up with collaborators in materials science, civil engineering, and biomedical engineering at Cornell and with Adele Boskey at HSS. They are measuring the mechanical properties of bone at the tissue level, modeling them across multiple scales, and correlating them with bone microstructure.

"It’s not really understood how the tissue bears the load, so we are working on how microscale properties relate to tissue and whole bone strength," says van der Meulen.

Working on All Levels

That approach illustrates a key vision embraced by the entire biomedical engineering field faculty at Cornell. "We need to—no matter the application, whether it’s tissue or organs—think about these problems quantitatively at different length scales and how all the different levels relate to each other," says Lawrence Bonassar, an associate professor with joint appointments in mechanical and biomedical engineering. "There’s a continuum that goes from molecules, to tissue, to organs. Biology tends to focus on the molecular level, and medicine is primarily concerned with organs, but the intermediate level, from 10 microns to the centimeter scale, gets neglected."

Using an atomic force microscope to examine a cross-section of a cortical bone osteon from an adult primate, van der Meulen’s research team can make measurements in the distinct layers that represent a gradient in tissue age. Osteons are the microstructural subunit of the shafts of long bones. Studying tissues from animals of different ages may help to determine the role of microstructure in the mechanical behavior of bones. (Samples are obtained from animals that have died from natural causes at the Southwest National Primate Research Center in San Antonio, Texas in collaboration with Dr. Adele Boskey at the Hospital for Special Surgery.) Provided

Like bone, cartilage is not a static material, although it’s not quite as adaptable. Even so, it’s incredibly durable. "Cartilage is an amazing tissue," says Bonassar. "It has some limited capacity to self-renew, but much more limited than other types of tissue, so essentially the same tissue survives 100 million cycles over 60 years."

Cartilage is not one material, but several working in concert, like carbon fiber reinforced plastic, but its behavior is a lot harder to understand. "One can think of cartilage very much as a composite tissue made of collagen fibers embedded in a gel of mostly water and proteoglycans," explains Bonassar. "The difference is that manmade composites are relatively simple. Biological materials are incredibly complex."

Another difference with manmade materials is that their properties—even in composites—are usually consistent throughout. "In general, biological materials aren’t like that at all," says Bonassar. "In particular, cartilage is not like that. Its properties vary with time, with position, and with development, and this is critical to the way that it functions."

Cartilage has three layers—the surface, middle, and deep zones. Bonassar’s lab has been very excited by recent results showing unexpected behavior in the area that old anatomy textbooks call the transition zone, between the surface and middle zones. "The tissue has a weak or compliant region just below the surface," says Bonassar. "It’s a great example of a case where there have been lots of hints in the tissue but until the experiments we performed, it was not all brought together."

With a new understanding of its properties, Bonassar thinks this area might be much more than a simple transition zone. "If you have a region that’s very compliant, that’s going to be good at absorbing energy," he says. "Blunting cracks is also something we think might be important."

Arthritis is thought to be a top-down disease, starting at the cartilage surface and propagating downward, with deeper changes occurring as the disease progresses. Bonassar plans to work with HSS to look at human cartilage in various states of disease and look at lubrication performance and performance of the transition region to see whether that changes. "We think lubrication and mechanical behavior of the transition zone could be key in starting or stopping the degeneration," says Bonassar. "We want to find out what goes on when things go wrong and connect that with function."

That kind of knowledge could help Bonassar’s group create a cartilage substitute, whether it’s totally artificial or tissue engineered. He’s already demonstrated a process for tissue printing with mechanical engineering Associate Professor Hod Lipson. "We’re very lucky that it’s easy to see the connections to the therapeutic applications of what we do," says Bonassar. "If we can identify special regions of tissue damaged early, and even specific molecular components that are damaged or enable the propagation of damage, that might inform therapeutic strategies for preserving function."

Such strategies will be crucial in meeting the next challenge facing orthopedics. "The Baby Boomers are coming to arthritis at a younger age because they’ve been more active and more injured," says Wright. "Now we see patients in their forties or fifties with the beginnings of arthritis."

The HSS surgeons will meet that challenge working with Cornell biomechanics researchers. And with two new faculty members, Jonathan Butcher and Yingxin Gao, their interactions are sure to grow in coming years. "I couldn’t be more proud to be part of this thing," says Wright. "It’s just an amazing effort. The surgeons love having high-powered engineering behind them."