Cartilage Regrowth: Steering Microfracture to Provoke Regeneration of Fully Functional Cartilage

Microfracture surgery is a poor approach to producing the regrowth of cartilage. It is a procedure that causes minor damage, and that damage in turn provokes a more extensive regeneration of joint tissue. The tissue is unfortunately not the same as normal cartilage, but is better than nothing in cases of serious damage or wear. Researchers here asked how this response to damage works, and whether it can be steered to produce fully functional cartilage instead of the present less optimal tissue.

Damaged cartilage can be treated through a technique called microfracture, in which tiny holes are drilled in the surface of a joint. The microfracture technique prompts the body to create new tissue in the joint, but the new tissue is not much like cartilage. Microfracture results in what is called fibrocartilage, which is really more like scar tissue than natural cartilage. It covers the bone and is better than nothing, but it doesn't have the bounce and elasticity of natural cartilage, and it tends to degrade relatively quickly.

For a long time, people assumed that adult cartilage did not regenerate after injury because the tissue did not have many skeletal stem cells that could be activated. Working in a mouse model, researchers documented that microfracture did activate skeletal stem cells. Left to their own devices, however, those activated skeletal stem cells regenerated fibrocartilage in the joint. But what if the healing process after microfracture could be steered toward development of cartilage and away from fibrocartilage? The researchers knew that as bone develops, cells must first go through a cartilage stage before turning into bone. They had the idea that they might encourage the skeletal stem cells in the joint to start along a path toward becoming bone, but stop the process at the cartilage stage.

The researchers used a powerful molecule called bone morphogenetic protein 2 (BMP2) to initiate bone formation after microfracture, but then stopped the process midway with a molecule that blocked another signaling molecule important in bone formation, called vascular endothelial growth factor (VEGF). "What we ended up with was cartilage that is made of the same sort of cells as natural cartilage with comparable mechanical properties, unlike the fibrocartilage that we usually get. It also restored mobility to osteoarthritic mice and significantly reduced their pain."

Link: https://med.stanford.edu/news/all-news/2020/08/Researchers-find-method-to-regrow-cartilage-in-the-joints.html