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Better microscope means better bones

The grant also enables Tomsia’s group to acquire an environmental field emissions scanning electron microscope, a fancy name for a microscope that allows researchers to view wet, and therefore biologically realistic, samples. In contrast, some high-resolution microscopes can only analyze dry samples, a drawback that prohibits researchers from analyzing samples in their natural environment. Tomsia will use the microscope to conduct the next phase of his research: scaffolding that pass mechanical property screening tests will be immersed in cell cultures that reveal precisely how live bone cells interact with the scaffolding.

Ultimately, Tomsia hopes to develop biomaterials that replicate the strength, porosity, and elasticity of real bone. The latter trait may lead to longer lasting implants. Because today’s implants are too stiff, they shield adjacent bones from the stresses of everyday life, such as the jarring bounce of walking. Unfortunately, bones don’t grow unless they are stressed (which is why astronauts lose bone mass). In the case of implants, stress shielding inhibits the continuous growth of new cells that keep joints healthy and strong, which, in turn, causes implants to loosen over time and require corrective surgery — a fate that befell 59,000 hip and knee replacements in 2000. Tomsia’s research could greatly reduce the number of these surgeries each year.

“I’m very interested in improving people’s lives,” Tomsia says, stressing the importance of teamwork. “We don’t have Leonardo da Vincis anymore. Nobody can do this alone — we have to work together.”


Scaffolding for the skeleton
Is it real, or is it hydroxyapatite? Synthetic tissue that looks and behaves like the real thing comes alive in this artist’s impression of next-generation scaffolding.

The collaboration will explore ways to make scaffolding, a fundamental building block in tissue engineering that provides a platform on which healthy cells can live and proliferate. This material, when thinly coated onto an implant, facilitates the all-important bond between the implant and surrounding tissue. Over time, as more and more cells inhabit the scaffolding, the implant becomes as enmeshed into the body as any bone.

But as important as scaffolding is to an implant’s success, researchers haven’t been able to fabricate material that both mimics bone’s strength and porosity, and is readily accepted by the body’s immune system. To meld these conflicting characteristics into a single biomaterial, Tomsia is pursuing two research initiatives. Both take advantage of bone’s relatively simple composition of calcium phosphate and collagen.

“Our material will have properties exactly like bone,” Tomsia says. “It will absorb stress, and it won’t cause immune responses and inflammation.”

The first approach relies on a calcium phosphate mineral called hydroxyapatite. Using nanosized particles of this mineral, Tomsia’s group has developed scaffolding that features a dense inner core with gradually increasing porosity toward the surface, like a cylindrical sponge with tiny holes near the center, and increasingly larger holes toward the exterior. This combination gives the scaffolding strength without sacrificing porosity.

Artificial knees could become less artificial thanks to Tomsia's research.  

To make the scaffolding even stronger, they infiltrate its layers with different polymers, with each successively deeper polymer layer less inclined to accept the influx of cells. When a scaffolding-coated implant is inserted into the body, bone cells incrementally invade the scaffolding — first occupying the outer layer, then the next layer, and the next — until the implant slowly becomes a part of the body.

The scaffolding is fabricated using stereolithography, a technique in which a three-dimensional object is poured layer by layer using liquid polymer and a computer-generated design. Tomsia’s laboratory has also developed a fabrication technique that uses liquid nitrogen to freeze cast calcium phosphate suspensions into the desired shape and porosity.

The second approach takes its cue from collagen, a fibrous protein substance that, along with calcium phosphate, is the main constituent of bone. Instead of using collagen, however, Tomsia is developing scaffolding from hydrogel, an organic polymer that closely mirrors the chemical properties of collagen. Like collagen, the polymer provides a staging ground for calcium phosphate to coalesce and begin building bone. Hydrogel scaffolding can also be applied in minute quantities, enabling it to foster the growth of bone tissue a few cells at a time. This nanoscale, targeted approach could help speed the recovery of bone fractures, or ensure that implants bind with surrounding tissue.

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Ernest Orlando Lawrence Berkeley National Laboratory