Another Potential Approach to the Creation of Tissue Engineered Cartilage

Cartilage is a comparatively simple, homogeneous tissue, and the medical community has a great deal of experience in treating cartilage injuries, so it is an obvious place to start for tissue engineers. Creating cartilage that has the correct load-bearing characteristics has proven to be a challenge, however: you can't just put cartilage cells into a bioreactor on their own and expect to obtain anything other than a sloppy gel at the end of the day. Fortunately, a number of groups have made progress in recent years on this front, finding approaches to convince the cells involved to generate the suitably structured extracellular matrix needed to form a solid, high-strength tissue. The method described here is one of the more straightforward ones:

Biomedical engineers have created a lab-grown tissue similar to natural cartilage by giving it a bit of a stretch. The tissue, grown under tension but without a supporting scaffold, shows similar mechanical and biochemical properties to natural cartilage. Articular cartilage provides a smooth surface for our joints to move, but it can be damaged by trauma, disease or overuse. Once damaged, it does not regrow and is difficult to replace. Artificial cartilage that could be implanted into damaged joints would have great potential to help people regain mobility.

Natural cartilage is formed by cells called chondrocytes that stick together and produce a matrix of proteins and other molecules that solidifies into cartilage. Bioengineers have tried to create cartilage, and other materials, in the lab by growing cells on artificial scaffolds. More recently, they have turned to "scaffold-free" systems that better represent natural conditions. The research team grew human chondrocytes in a scaffold-free system, allowing the cells to self-assemble and stick together inside a specially designed device. Once the cells had assembled, they were put under tension - mildly stretched - over several days. They showed similar results using bovine cells as well. "As they were stretched, they became stiffer. We think of cartilage as being strong in compression, but putting it under tension has dramatic effects."

The new material had a similar composition and mechanical properties to natural cartilage, the researchers found. It contains a mix of glycoproteins and collagen, with crosslinks between collagen strands giving strength to the material. Experiments with mice show that the lab-grown material can survive in a physiological environment. The next step is to put the lab-grown cartilage into a load-bearing joint, to see if it remains durable under stress. "The artificial cartilage that we engineer is fully biological with a structure akin to real cartilage. Most importantly, we believe that we have solved the complex problem of making tissues in the laboratory that are strong and stiff enough to take the extremely high loads encountered in joints such as the knee and hip."



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