Mar. 28, 2006 A breakthrough self-assembly technique for growing replacement cartilage offers the first hope of replacing the entire articular surface of knees damaged by arthritis. The technique, developed at Rice University's Musculoskeletal Bioengineering Laboratory, is described in this month's issue of the journal Tissue Engineering.
"This has significant ramifications because we are now beginning to talk, for the first time, about the potential treatment of entire arthritic joints and not just small defects," said lead researcher and lab director Kyriacos Athanasiou, the Karl F. Hasselmann Professor of Bioengineering.
Athanasiou's new self-assembly method involves a break from conventional wisdom in bioengineering; almost all previous attempts to grow replacement transplant tissues involved the use of biodegradable implants that are seeded with donor cells and growth factors. These implants, which engineers refer to as scaffolds, foster the tissue growth process by acting as a template for new growth, but they always present a risk of toxicity due to the fact that they are made of materials that aren't naturally found in the body.
In the newly reported findings, Athanasiou and postdoctoral researcher Jerry Hu, using nothing but donor cells, grew dime-sized disks of cartilage with properties approaching those of native tissue. In a follow-up study due for publication soon, graduate student Christopher Revell refined the process to produce disks that are virtually identical to native tissue in terms of both mechanical and biochemical makeup. In a third, and perhaps most impressive breakthrough, Athanasiou and Hu used the self-assembly approach to grow the entire articular surface of the distal femur. Each of these unbroken samples were tailored three-dimensionally to fit a specific rabbit femur.
"If you told me 10 years ago that we would be making entire articular end caps via self assembly I would have said you were crazy," said Athanasiou. "The fact that we can do this is an indication of how far the discipline of tissue engineering has progressed."
Unlike cartilage, most tissues in our bodies -- including skin, blood vessels and bone -- regenerate themselves constantly. Tissue engineers try to capitalize on the body's own regenerative powers to grow replacement tissues that can be transplanted without risk of rejection. Donor cells from the patient are used as a starting place to eliminate rejection risks.
Most tissue engineering involves honeycombed plastic templates or hydrogels called scaffolds that are used to guide colonies of donor cells. Donor cells can be either adult stem cells or other immature cells. Athanasiou's latest work was done using chondrocytes, or cartilage cells.
Athanasiou, a former president of the international Biomedical Engineering Society, helped pioneer the development of coin-sized scaffolds in the early 1990s that are now the state-of-the-art clinical option for repairing small defects in articular knee cartilage.
His lab is also working on techniques to grow replacement knee menisci, the kidney shaped wedges of cartilage that sit between the femur and tibia and absorb the compressive shock that the bones undergo during walking and running. Over the past 18 months, he and his students Adam Aufderheide and Gwen Hoben have perfected methods of growing meniscus-shaped pieces of cartilage, but they are still trying to perfect the mechanical strength of the engineered meniscus tissue, which must be able to withstand up to an astounding 2,400 pounds per square inch of compressive pressure.
Athanasiou's research is funded by Rice University and the National Institutes of Health.
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