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Lazy Bones

Bor Jang has built a crude machine so his mechanical engineering students can experiment with a process called free-form fabrication. The gadget, which looks a bit like a mutant drill press connected to a desktop computer, is a highly maneuverable nozzle. Actually, it's a robot with one or two nozzles, which are capable of moving in three dimensions: height, width and depth. The computer manipulates the nozzles to perform an intricate dance — up and down, in and out, back and forth — until they create a three-dimensional plastic object. A collection of beige plastic vases and oddly shaped sculptures adorn a set of bookshelves in the lab in Dolve Hall at North Dakota State University, simple testaments to free-form fabrication, objects made without a mold.

A much more sophisticated counterpart machine of Jang's design can be found at NASA's Johnson Space Center in Houston. The space agency is interested in the possibility that, someday, computer-assisted-design specifications for replacement parts could be beamed up to a fabricator onboard a spacecraft or space station, a means for machines to regenerate mechanically. But Jang, who has 16 or 17 patents in free-form fabrication, together with a team of colleagues at NDSU, is engaged in research that's much more down to earth, involving an application for people, not machines: tissue engineering bone.

Bone holds many marvels. Its components are living and nonliving, hard and soft, solid and porous. An intricate honeycomb interior enables bone to provide the strength of steel with the weight of aluminum — and, unlike inanimate metal, broken bones perform the trick of healing themselves. But it turns out that, given the chance, our bones really are lazy. This becomes a problem when diseased or broken bones are given artificial substitutes. Take the hip replacement, for example, a common therapy for elderly arthritis sufferers. A surgeon removes the diseased hip and replaces it with one made of plastic or metal, allowing the recipient to keep walking. Gradually, however, the surrounding bone, which no longer carries its customary burden, becomes "lazy" and deteriorates. Then, maybe eight or ten years later, the replacement hip must be replaced — subjecting the patient once again to painful major surgery.

To get around the shortcomings of artificial bone replacements, Jang's team is trying to find a way of building a latticework "scaffold" — a honeycomb structure similar to bone's natural honeycomb interior — inserted surgically to provide support so the bone can better heal itself. In his office, Jang keeps a beige plastic prototype of a scaffold, with honeycomb chambers to allow room for new bone cells to adhere and grow.

"Then the beauty of this is we can design a material in such a way that it can be absorbed by the body gradually," Jang says, "so you don't need an additional surgery step to remove it." For that to happen, his team is searching for a material that will break down and be absorbed by the body's natural metabolic processes. "Disappearing" medical materials have been used for years, as in the case of surgical stitches that dissolve.

The task becomes much greater, though, when the material must serve as a support structure, or scaffold. Also, each scaffold must be individually tailored for a patient's size and shape. The idea is to take a CT or MRI scan, which can provide 3D pictures of a hip joint or knee bone, and use the image to fabricate a scaffold of exactly correct proportions. Also, in the early stages, the material must be capable of helping new bone cells thrive and multiply, gradually eliminating the need for the scaffold. By altering the structure, engineers can control the rate at which the scaffold dissolves.

The challenges that must be overcome are many and complex, however, in order to devise a suitable "biocompatible" scaffold. To succeed, specialists in many disciplines will work together. Jang's NDSU collaborators include Josh Wong, a fellow mechanical engineer and materials scientist; Qun Huo, a polymer chemist; James Stone, a design and modeling engineer; Kalpana Katti, a bio-physicist and material scientist; Dinesh Katti, a structural analyzer; and D.K. Srivastava, a biochemist. The NDSU team, in turn, is working with five biomedical specialists at the Mayo Clinic, where Stone once worked. "So we have a team of 10 or 11 really topnotch scientists," Jang says. "It's fun to work together. It's a very cooperative team."

Lazy Bones

Research teams all over are working on tissue-engineering projects, including biocompatible scaffolds. But the NDSU team brings an established track record to the initiative. Besides Jang's success, as measured by the patents he has obtained, other members have received major research funding for their work. Huo, for instance, has approximately $500,000 in support from the National Science Foundation for her work involving gold nano-particles. Katti has received NSF grants of $75,000 and $375,000 to design new composite materials for bone replacement. "We are not just jumping on the bandwagon," Jang says. "We have a very good team. We can make very significant contributions in the future, I believe."

The bone tissue-engineering collaboration, which recently formed, hopes to receive funding support from outside the university. "But in the meantime we are doing it without research support," Jang says. "I have been very successful in the past in securing research funding." Among other things, Jang needs a much more advanced fabricator. "We are trying to build a very sophisticated version," he says. Jang and other members of the team hope to know if their work is on a promising path within a couple of years. If they succeed in developing biologically compatible bone scaffolds, clinical trials would be conducted at Mayo Clinic.

Jang is convinced that the convergence of free-form fabrication and tissue-engineering technologies will revolutionize medicine. Imagine, for example, that a tourist badly injures his knee while climbing the Great Wall outside Beijing. A Chinese clinic could transmit MRI images to a center at Mayo Clinic, which could fabricate a scaffold, then FedEx it to China. Or, if the patient already had an MRI of the injured part, the center at Mayo Clinic could transmit computer-assisted-design specifications for the scaffold to the Beijing medical center, where it could be inserted surgically.

"There are so many different things that can be done by using this technique," Jang says of free-form fabrication. Researchers hope that tissue engineering could provide the solution to the chronic shortage of transplant organs. "In the long term we are hoping to develop artificial organs," Jang says. "That would take hard work from many scientists, not just the group here."



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