With a new child as inspiration, a husband-and-wife team have set out to solve the daunting problem of how to imitate nature’s growth of the human bone.
Like all new parents, Amit Bandyopadhyay and Susmita Bose are awed by the perfection of their new son.
But Bandyopadhyay and Bose, a husband-and-wife research team in the School of Mechanical and Materials Engineering at Washington State University, have more appreciation than the average parent for how truly difficult it is to achieve that perfection. For much of their young careers, they have worked to develop a good imitation of just one part of their perfect son-his bones.
“It’s very difficult to mimic nature,” says Bose.
Being able to develop a good bone imitation with the same physical, mechanical, and biological properties as real bones would be invaluable to the medical community. As a high percentage of the U.S. population moves towards retirement age, increasing numbers of people are suffering from age-related bone problems, such as arthritis. Other bone problems can occur for a variety of reasons, from cancer to injuries to rheumatoid arthritis. Every year, approximately 800,000 bone grafting or replacement procedures are done in the U.S.
For people with damaged bones, current treatments call for the use of either metal screws or plates, or portions of bone from other parts of their own bodies or from the bodies of others. The first successful joint replacements were done more than 40 years ago, when steel implants were fixed to hip bones by means of an acrylic cement. Although the technology remains largely unchanged, it now uses lighter-weight metals and better cements.
However, current treatments with metal implants do not necessarily cure people permanently. Metal can release ions into the body, with potentially long-term negative health effects. Also, because the metal pieces are stronger than bones, the body relies on the metal pieces to take stress and weight. The lack of stress on surrounding bones eventually makes them weaker, just as bones that don’t get weight-bearing exercise become weak.
State-of-the-art hip replacements are currently made of mostly titanium-based alloys. They are low-density and can carry weight. However, the lack of tissue bonding and significantly higher stiffness compared to natural bone limits their average lifetime to about 10 years. Despite substantial efforts to improve them, the durability of metal bone replacements has not improved.
Using real bone pieces for bone grafting also creates problems. When bone pieces are taken from the patient’s own body, two surgeries are required, creating additional trauma for the patient. Bone pieces taken from other people’s bodies carry the chance of rejection or transmission of viral diseases.
To build the perfect bone, Bandyopadhyay and Bose started with detailed images of bones. Medical imaging has advanced greatly in recent years, so a computer tomography (CT) scan or magnetic resonance imaging (MRI) can give a very good picture of what a bone problem looks like.
The researchers in this case took a CT scan of a horse hoof submerged in water to simulate the tissue that would surround a real bone. The information from the CT scan was used to construct a computer automated design (CAD) file. The CAD file was programmed to provide instructions to a fused deposition modeling machine, which uses a technology called rapid prototyping to build the bone imitation. This is a familiar technology to Bandyopadhyay. In the late 1990s, he received a prestigious Young Investigator Program award from the Office of Naval Research and the CAREER award from the National Science Foundation for his research on rapid prototyping.
Based on the information in the CAD file, the head of the fused deposition modeling machine moves like a fancy glue gun, squeezing out a heated polymer. Building one layer at a time, the machine generates a three-dimensional model. Similar to the way in which one can make either contact prints from a photographic negative or finished prints in a variety of sizes, the process can be used to make either the controlled porosity structure itself with a specific shape and size, or a mold of it. Using the horse’s hoof and a “negative” of a plastic bone model, Bandyopadhyay and Bose worked with their graduate student, Jens Darsell, to create an artificial ceramic bone graft. The sophisticated ceramic bone model perfectly imitates the shape and complicated porous architecture of a real bone.
ENTER THE BIOLOGIST
The bone implant looks perfect, as perfect as the real thing. But looks can be deceiving.
For a bone implant to work, real bone cells need to be able to grow on it in the same way that bones grow in a newborn baby. So the materials engineers contacted Howard Hosick, professor in the schools of Molecular Biosciences and Biological Sciences. Hosick began working with Bandyopadhyay and Bose to assess how live bone cells interact with the fine porous architecture of their bone imitation. Bone cells grow differently depending on the porosity of the implant. Hosick and his research group have addressed questions such as adhesion to find out which bone implant materials allow the most real bone cells to bond to them. He also has looked at how cells grow and differentiate on the bone implant.
Hosick says that throwing together scientists with very different expertise is exactly when research starts getting fun.
“We’re getting to the real action,” he says.
BRINGING BONES TO HOSPITALS AND THE REGIONAL ECONOMY
Bandyopadhyay, Bose, and Hosick would like to connect patients to their research. For years, regional leaders have been working to get biomedical research expertise at WSU together with clinicians at area research hospitals. Community leaders have become aware that the researchers’ bone work could be a positive step in that direction, and the investigators have recently applied for grants to foster economic development through creation of a biotechnology center in the region. The idea is to link some of the innovative research in biomedicine with people who can use it-physicians and hospitals in the Spokane area.
“In Spokane, we have a terrific medical community with world-class physicians, and at WSU, we have wonderful basic science,” says Hosick “This would be a seed to put these strong components together.”
MEANWHILE, BACK IN MATERIALS . . .
Bandyopadhyay and Bose are still working to improve their bone implants, particularly in strength. Like human bones riddled with osteoporosis, the intricately constructed bone imitations have a tendency to crumble.
Although they used the same materials that are in bone, something appears to be missing. To simulate the properties of real bones Bandyopadhyay and Bose thought of taking their recipe to the nanoscale, or molecular level. If they can create a powder in nanometer grain size, which is one-billionth of a meter, they theorize, they create more surface area to which the particles can bond. The resulting material will be stronger.
Bose focused her research to synthesize ultrafine powders of calcium phosphate-based ceramics using novel processing methods. So far, the researchers have brought the particle size down to 50 nanometers, or 1/2000th the diameter of a human hair They have found that these nanometer-sized particles of calcium phosphate bond more efficiently than commercially available powder. They are also working to add to their recipe other mineral ions that are typically found in the human body. They hope that adding minute amounts of magnesium or sodium will strengthen their bone while avoiding the body’s tendency to reject foreign materials. Bose recently received a Faculty Early CAREER Development Award from the National Science Foundation to continue this work.
ORE LOOK AT PERFECTION
Since the arrival of their son last summer, Bandyopadhyay and Bose have participated in many of those middle-of-the-night events so common to parenthood. Peering into his crib, they’ve watched in wonder as their son takes his perfectly-made thumb and finds his tiny mouth.
“It’s just not easy to imitate that,” says Bose.
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