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Cartilage is the body's shock absorber, a cushion of durable tissue that protects the knee from a lifetime of walking, bending and running. Though just a few millimeters thick, cartilage is nevertheless quite complex, consisting of a surface, middle and deep region, each with its own distinct composition and structure.

Now a team of bioengineers at the UC San Diego School of Engineering has described in detail for the first time what happens to each of these regions when cartilage is squeezed and flattened as it absorbs impact.

The results present a blueprint for the mechanical properties of cartilage and how it works in the body, valuable information for engineering laboratory grown knee cartilage to replace damaged tissue. Many biotechnology companies are beginning clinical trials with such tissue substitutes.

The study will be published in the fourth issue of the Journal of Orthopaedic Research, which was released September 29. The authors include Robert Schinagl, a Ph.D. student in bioengineering, and Robert Sah, associate professor of bioengineering.

"One approach to engineering replacement cartilage tissue is to inject cells into a scaffold, and direct the cells to secrete tissue components that form cartilage. However, it is important to understand exactly how normal tissue functions in order to design and test replacement tissues," said Sah. "Understanding normal function could also help in identifying ways to treat arthritic and aging cartilage tissue."

In the study, Sah and his students took the first quantitative measurements of the compression of knee cartilage. It has been suspected that cartilage is relatively soft and flexible at the surface, but stiff closer to the bone. Sah's findings support this theory and provide detailed measurements.

During the study, the researchers used a novel technique to identify cartilage cells, called chondrocytes, within the cartilage tissue layers. As they compressed the tissue, they recorded images seen in a microscope, and tracked the motion of the chondrocytes. By viewing the results, they could make the first detailed observations about the compressive mechanical properties in the different regions of the cartilage tissue. They found that the surface region of cartilage was 5 times softer than the average, while the deep tissue closer to the bone was 5 times stiffer than the average. The surface region of the knee cartilage was 25 times softer than the deepest region. Previous studies have only characterized the average properties of the entire tissue.

According to Sah, the next step to the research will be to determine if the healing of tissue-engineered cartilage implants, which involves fusion with the surrounding host tissue, can be helped by "matching" the layer-dependent material properties of the implant to that of the surrounding host cartilage.

Sah is also a co-investigator on a new five-year, $4 million Program Project Grant of the National Institutes of Health on cartilage tissue in aging and osteoarthritic joints. Martin Lotz of the Scripps Research Institute leads the project team. One aspect of the study is to implant engineered cartilage tissue in animals and determine if there is any difference in healing between young and older animals.

Sah's study was sponsored by grants from the Arthritis Foundation, National Institutes of Health, National Science Foundation, and Whitaker Foundation. Schinagl has accepted a position with Osiris Therapeutics, a biotechnology company in Baltimore that is working on cartilage replacement therapies.

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