Sima Bahadori, seated, left is biomedical scientist Gabriela Loots, and on the right is Lawrence Fellow Nadeen Chahine.
Nanotubes at Livermore
October / November 07
Volume 5 Number 5
Sima Bahadori knew that even if she became a teacher instead of a scientist, she wanted to first make hands-on use of the knowledge she was learning as a biology student at California State University in Hayward. She landed an internship at Lawrence Livermore National Laboratory's pilot Aspiring Teacher program in the summer of 2007, investigating the potential use of carbon nanotubes as tissue scaffolding for cartilage growth and joint regeneration.
Nearly 500,000 hip and knee replacements are performed annually in the United States, relieving pain and restoring mobility to patients whose joints have been damaged by arthritis or other illness or injury. Smooth, cushioning cartilage will normally help joints move freely and absorb impact. However, when damaged, cartilage does not sufficiently restore itself, leading to more pain and degeneration. The limited repair ability of the native tissue has propelled interest in creating a biological replacement for damaged cartilage. In tissue engineering, cells are grown with scaffold materials to create a biologically functional replacement. To date, however, the science has shown that cultured cells do not produce enough strength-inducing matrix molecules, such as collagen, for the cultured tissue to bear weight in a joint replacement.
"It would be crushed within a few steps," said Bahadori's research team leader, Nadeen Chahine. She devised the project knowing that carbon nanotubes had only been minimally explored for use in bioengineered tissue since their development in the 1990s.
At one 80,000th the width of a human hair, nanotubes have matured from a laboratory curiosity and even a speculative science fiction ploy featured in such books as Arthur C. Clarke's The Fountains of Paradise. Their promise was addressed in the 1959 talk by the late Nobel Laureate physicist Richard Feynman, "There's Plenty of Room at the Bottom." They have now become a commercial reagent available to explore in real-world applications.
Feynman told fellow members of the American Physical Society, who were gathered for their annual meeting at Caltech, "It is a staggeringly small world that is below. In the year 2000, when they look back at this age, they will wonder why it was not until the year 1960 that anybody began seriously to move in this direction."
Chahine brought the nanotube project to the laboratory in the fall of 2006, when she accepted a three-year Lawrence Fellowship. That same year, an unprecedented application of nanotubes may have contributed to Floyd Landis's victory in the Tour de France. The carbon-fiber bicycle frame he rode had nanotubes added to resin that bound the fiber, contributing strength while conserving weight.
Chahine has a doctorate in biomedical engineering from Columbia University. She was drawn to the question of how cartilage in a healthy joint maintains tensile strength far beyond the possibilities of any manmade material, bearing repeated stress for a lifetime. With the opportunity to lead her own research projects over the course of three years of the prestigious post-doctoral fellowship, she would like to understand what factors generate tissue that performs so well in nature.
"Just by walking, you put two to three times your body weight on your knee," she explained. "If you jog or run, the load can be anywhere between four and eight times your weight."
Carbon nanotubes are hollow cylinders of graphite about a nanometer in diameter. They form spontaneously in vapor from arc welding, and can also be manufactured. The molecular structure of their cross-linked atoms somewhat resembles the pattern of a cyclone fence. Wrapped around a hollow space, the thin sheets create narrow tubes that are more strong than dense.
Carbon nanotubes are attractive for bioengineering due to their potential to be chemically compatible with living tissue. This interdisciplinary research at the laboratory takes place in the Center for Micro and Nano Technology, where such cross-cutting challenges are the norm. Director Anantha Krishnan, Chahine's mentor, calls the center's 50 technical members "quite a forward-looking group." Their contributions can be found in a variety of lab programs, from weapons and fusion energy to sensing and high-speed optical data acquisition. Besides intellectual capital, the center houses capabilities such as a class 100 clean room that can pattern silica, glass and polymers. Overall, activities there are split between emerging and applied research.
Collaborations often involve Stanford and the Berkeley and Davis campuses of the University of California; UC researchers at campuses in Irvine, Santa Barbara and Los Angeles; and more far-flung institutions such as the University of Illinois at Champaign-Urbana and MIT.
Nanotechnology research in the Livermore center spans a variety of structures ranging from dots, wires and pores to tubes. Nanotubes have potential medical utility by serving both as structural material and a delivery system for drugs. Their unique electrical and optical qualities have also generated interest in novel or improved applications in sensing, microelectronics and optics.
Bahadori and her mentors are especially enthused about beginning to tap the promise for applied research that merges the mechanical and medical, blending unique properties of nanometer-sized structures with living systems in a way that could potentially alleviate human suffering. Besides Chahine, Bahadori also worked with post-doctoral fellow Nicole Collette in the biosciences and biotechnology division in the laboratory of Gabriela Loots, a molecular and cellular biologist experienced in developmental biology. The group first extracted and cultured cartilage cells from cow joints. Bahadori then grew the cells in agarose gel that contained a suspension of the black, powdery nanotubes for scaffolding, and subsequently subjected the composite disks to biomechanical tests. To potentially enhance biocompatibility, the nanotubes were pre-treated with either a coating of carboxylic acid, which is already present in cartilage, or chemically inert polyethylene glycol. The cells grew better in the neutral environment. However, the resulting network was not as dense, according to Bahadori's final mechanical tests.
She remarked at the end that the internship offered a chance to "utilize all the knowledge I had so far built up and get more functional, so I will be able to transfer all this knowledge to someone else. I wanted to make the most of the learning in a real research environment; it makes me more comfortable and confident."
Following up Bahadori's studies, Chahine would like to try using bone marrow adult stem cells from cows, or perhaps mice, to regenerate cartilage on nanotube scaffolds. She envisions ultimately using carbon nanotubes not only for physical support, but also to release growth factors to guide cartilage development and deliver drugs to treat inflammation or other conditions.
Chahine said Bahadori was a perfect match for the project. In addition to her coursework in cell and molecular biology, she earned a degree in chemical engineering, and worked in computers and high technology. Her training includes a degree in chemical engineering from Middle East Technical University in Turkey, as well as work in computers and high technology in the U.S. That background allowed her to rapidly pick up and apply interdisciplinary concepts.
"The beauty was I ended up in a project that combines both science and engineering," Bahadori says. "The more I got into it, the more I liked it."
Nancy Garcia is a science writer at Lawrence Livermore National Laboratory.
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