Monday, June 16, 2008

Regenerating Lost Cartilage

A surface textured with carbon nanotubes could encourage cells to grow.

By Courtney Humphries

Growing cartilage: A cartilage cell grows on a textured surface coated with carbon nanotubes. Credit: Thomas Webster

The key to coaxing cells to regenerate might be to make things a little rough for them. Thomas Webster, a bioengineer at Brown University, has been developing implantable materials with nanoscale textures to mimic the roughness of living tissues.

Now, his team has found that cartilage cells can adhere to and grow more densely on a surface covered with carbon nanotubes, particularly when they are also exposed to electrical stimulation. Webster believes that surfaces incorporating carbon nanotubes, which are not only textured but are also electrically conductive, could be a promising strategy for designing cartilage implants.

Cartilage has limited ability to heal itself, so loss or injury to the cushioning tissue is a major health problem. Many research labs have developed materials that mimic the properties of cartilage, as well as scaffolds that can be seeded with cartilage cells outside the body and then implanted at the site of cartilage loss. But one of the key problems is getting a patient's native cartilage, a spongy and rather inert material that lacks its own blood supply, to attach to and integrate with an implant.

To construct a more cell-friendly surface, Webster's team used carbon nanotubes, which have a rough surface and also readily conduct electricity. The researchers mixed the nanotubes into sheets of polycarbonate urethane, an FDA-approved polymer. When they cultured cartilage cells on these sheets, the cells grew more densely on the roughened surface versus on a smooth polycarbonate surface.

Cells grew even faster when the nanotubes were electrically stimulated, although it's not clear why. "Most people believe it's changing the membrane potential of cells," Webster says, which would increase the number of calcium ions--an important cellular signal--flowing into the cell.

Why do cells seem to like rough surfaces? Webster believes that the nanostructures change the surface properties of a material, helping it attract proteins that cells stick to. His work creating a nanostructured surface for bone implants has been licensed by a startup company called Nanovis, which hopes to take it into human trials. Webster's team has also shown that cells of vascular tissue can adhere better to nano-textured surfaces, which could be used to design better vascular stents. He believes that carbon nanotubes could be incorporated into materials used to make cartilage implants.

But Jennifer Elisseeff, a tissue engineer at Johns Hopkins University, is skeptical that the current study, in which cartilage cells were grown in a single layer, has any relevance yet for cartilage regeneration. "Cartilage really needs a 3-D scaffold," she explains, and it can be difficult to translate how cells behave on a flat surface to how they behave in a three-dimensional tissue. Webster's team is currently examining whether cells grown in this way are functionally active as cartilage cells and whether they can be combined into multiple layers.