The body is quite good at repairing itself, but some parts of our anatomy have difficulty recovering after an injury.
One such material is cartilage – the spongy but tough connective tissue that prevents our bones from rubbing and bumping against each other. Over time, the translucent or “hyaline” components of cartilage can become severely broken down, leading to painful conditions such as osteoarthritis and chondromalacia.
Scientists have been working on a method for regenerating hyaline cartilage for years. Now a team led by Northwestern University in the USA has achieved a breakthrough. They have developed a biomaterial that, when injected into the damaged cartilage of living sheep, acts as a scaffold and promotes cartilage growth in active joints.
“Cartilage is an important component of our joints,” says chemist Samuel Stupp of Northwestern University.
“When cartilage becomes damaged or degrades over time, it can have a significant impact on people’s overall health and mobility. The problem is that cartilage in adult humans has no inherent ability to heal. Our new therapy can induce repair of a tissue that does not naturally regenerate. We believe our treatment could help address a serious unmet clinical need.”
Cartilage damage is a massive health problem. A 2011 survey of 18 countries found that over 1.3 million knee replacement surgeries are performed each year, with cartilage problems being one of the leading causes.
And while there are other procedures that can help, such as creating microfractures to repair cartilage, these often result in the growth of the wrong type of cartilage—tough, fibrous fibrocartilage—like cartilage scar tissue—instead of the smooth, springy hyaline cartilage that covers joints.
One potential treatment that scientists are refining is the use of scaffolds in cartilage defects that support the growth of hyaline cartilage. This option has shown promise in small mammals such as mice, but fails in larger mammals, likely due to the greater stresses and forces experienced by the joints of larger animals.
Stupp and his colleagues have developed a material that seems to solve this glaring problem. It is a biomaterial that consists of two components.
The first is a peptide molecule that binds to a protein called transforming growth factor beta-1, which plays a crucial role in the growth and division of cells, particularly in the skeleton, where it regulates the growth of bone and cartilage.
The second ingredient is hyaluronic acid, which you may recognize from your skincare products – it helps your skin stay soft by retaining moisture. It is also found in joints and cartilage, where it acts as a lubricant and plays a role in wound healing.
The researchers found in test-tube experiments that this hybrid material supported chondrogenic differentiation – the proliferation of cartilage cells called chondrocytes. It formed bundles of filaments, a natural structure found in musculoskeletal tissues.
Many research approaches have reached the same point in vitro. The true test would be how the results hold up in a living animal, which can be extrapolated to humans. Sheep are subjected to similar mechanical stresses as humans, so the tests were conducted on sheep.
The researchers developed a paste from their material that was injected into cartilage defects in the hind knee joints of sheep. The researchers drilled small holes in both hind knees of each of the sheep studied; one knee was injected with the paste, the other remained untreated as a control.
When the slurry came into contact with the calcium in the sheep bones, it hardened into a rubbery matrix, and chondrocytes began to form, growing and filling the resulting hole as the scaffold was broken down. And it was the right kind of cartilage: hyaline. Within a few weeks, the treated defects showed remarkable improvement, especially compared to the control groups.
A similar treatment might be even more effective in humans. You can’t tell a sheep to rest and take the weight off its injured leg, while patients being treated for cartilage injuries are often immobile after surgery.
Of course, more research and development is needed, and then the procedure will need to undergo clinical trials in humans, but the results suggest that one day a treatment will be available that will help reduce the need for more invasive and less effective options.
“By regenerating the hyaline cartilage,” says Stupp, “our approach should be more resistant to wear and tear and solve the problem of limited mobility and joint pain in the long term. At the same time, the need for joint reconstruction with large implants is avoided.”
The study was published in Proceedings of the National Academy of Sciences.
