The Johns Hopkins University
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Occasionally, we think nature could do better. It would be nice if we had a limitless tooth supply, like sharks. And the fact that cartilage does not regenerate itself is a very real pain, especially in joints like the knee. Cartilage is formed when a special bunch of cells, called chondrocytes, excrete an extracellular matrix containing collagen (among other things). This matrix provides the unique mechanical and lubricating conditions we need in our joints. In healthy tissue, the chondrocytes keep churning out the extracellular matrix as needed, and we move about without giving it a thought. But lose those chondrocytes to a disease like arthritis, and it’s curtains for your cartilage. They don’t regenerate. Even the best polymer replacements degrade over time and have to be replaced every two years or so.

Prof. Ramesh is working with Dr. Carmelita Frondoza, a cell biologist in the Department of Orthopedics at JHU’s School of Medicine, on a different approach; using harvested chondrocytes to create living tissue that can replace cartilage. Unfortunately, this is anything but straightforward. The type of collagen matrix excreted by the chondrocytes depends on whether they receive the correct mechanical stimulation. Inside the body, the cells experience a mechanical load and generate the right kind of collagen. Outside the body, if the cells experience no load, the matrix produced is stiff and inflexible, resembling scar tissue instead of cartilage. Theory holds that these cells have little “receptors” that sense load/deformation changes, and in response, the cell produces a certain type of collagen. Create a mechanical load on the harvested cells, and they might excrete the right kind of collagen. But what kind of load? And is it the load itself or merely the deformation caused by the load that causes the cells to do what they do? If they could figure out the kind of mechanical environment the cells want to “see,” says Prof. Ramesh, then they could optimize the engineering of replacement cartilage.

To explore this, Prof. Ramesh takes living cells and places them in artificial “scaffolds” made out of an inactive polymer. Then he subjects the whole scaffold to various loads or deformations. Afterward, he and Dr. Frondoza extract the cells and examine how the cells grow and reproduce while under the load, to find the appropriate load needed to generate tissue at an accelerated rate for eventual implantation into a joint.

The work done by Profs. Ramesh and Frondoza on cartilage cells may one day be applied to problems involving other cell types (e.g., bone cells), in the hope that by engineering living tissues, various debilitating conditions might be eased or cured.

 

 

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