Understanding Gender Differences in Cartilage Cells Brings Hope for Better Spinal Disc Repair

Was their thinking biologically relevant?

Asking that question led the Georgia Institute of Technology professor and Georgia Research Alliance Eminent Scholar to collaborate with her colleagues in the development of several patent-pending technologies that may offer a significant improvement in the treatment of spinal disc damage and disease. The technologies are the basis for Boyan's startup company, which hopes to tap the $3-billion-a-year market for spinal disc repair.

Thirty years of research have informed Boyan's understanding of how bone and cartilage cells behave. Determined to discover the reasons why some people - women, in particular -- have a greater propensity for cartilage degradation over time, Boyan focused her attention on differences at the cellular level. There, she and her colleagues made the remarkable finding of biochemical differences between male and female cartilage cells in both animals and humans.

"There is a fundamental difference in these cells in males and females," says Boyan, the Price Gilbert Jr. Chair in Tissue Engineering and deputy director of research for the Georgia Tech/Emory Center for the Engineering of Living Tissues. "Now we want to understand the mechanism involved in this difference."

Boyan's research team is exploring whether females possess special steroid hormone receptors or whether their receptors just operate differently. This mechanism is of critical importance to bodily functions such as cartilage and bone formation, and probably affects a person's risk for diseases such as osteoporosis, osteoarthritis and some cancers, Boyan explains. Researchers elsewhere recently found biochemical differences in colon cancer cells in males and females.

"So this is a very important question for how you do tissue engineering, but also in general how you would treat males and females differently when there is a clear sex-specific effect," says Boyan, also a faculty member in Georgia Tech's Petit Institute for Bioengineering and Bioscience.

This finding on the sex specificity of cartilage cells led Boyan and her colleagues to question the ways scientists study cells. For example, most laboratories culture cells on tissue-culture plastic, which is not a natural surface. Yet bone and cartilage cells live in a complicated environment inside the body.

"So we started examining how cells respond to more biologically relevant surfaces and how those responses are regulated by steroid hormones," Boyan explains. "We found that micro- and nano-topography of surfaces can regulate cell growth."

Subsequently, Boyan and her colleagues, Professor David Ku and Associate Professor Robert Guldberg of Georgia Tech and former Georgia Tech VentureLab fellow Steve Kennedy, designed a more natural microstructure for the surfaces of hydrogel biomaterials used to replace defective bone and cartilage in the body - in particular, spinal discs.

By early 2003, the early-stage technology had proven its potential for commercialization, and Boyan received a VentureLab faculty commercialization grant, funded in part by the Georgia Research Alliance, to form a company called Orthonics. Kennedy serves as the CEO for the company, which is seeking its first round of investor financing. Orthonics is housed in the Advanced Technology Development Center's Biosciences Center on the Georgia Tech campus.

Orthonics' first product will be a "bionic spinal disc" for replacing diseased or damaged intervertebral discs in millions of people with severe chronic back pain. Currently, doctors performing disc surgery typically remove the inflamed cartilage and fuse two vertebrae together. This procedure reduces the patient's pain, but also their mobility.

"If we can come up with a material that behaves like a normal disc and helps patients retain their mobility - and I think we can - it will have an important impact on people's health and quality of life," Boyan says.

Orthonics researchers are studying whether the hydrogel's microstructure encourages cells to sufficiently multiply and become bone cells - promoting the bionic disc's attachment to vertebrae and not forming scar tissue, Boyan says. Researchers are following a similar line of study on cartilage cell formation on the hydrogel surface.

Laboratory experiments have yielded promising results for the bionic spinal disc, says Orthonics CEO Steve Kennedy. He expects that pre-clinical trials in animals will begin in early 2004, followed by clinical trials in humans by 2006. Like other medical devices, it will require FDA approval for use in the United States.

The bionic disc is made from a tough and rubbery hydrogel material similar to one used in contact lenses, Kennedy explains. Because of the material's similarity to natural tissue, bone and cartilage will grow into it. The device could be inserted in the spine in an arthroscopic procedure. Recovery time would range from one to six weeks, compared to as much as 15 months of recovery from spinal fusion surgery.

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