Cartilage damage in the knee, for example due to injuries or arthrosis, can hardly be healed to date. Researchers have now tested a new approach on rabbits: They implanted a biodegradable scaffold made of nanofibers in the affected joint. This was designed in such a way that, driven by the movements of the rabbit, it generated an electrical voltage. This stimulates the cells to form new cartilage. In the animals treated in this way, the damaged cartilage tissue healed almost completely within one to two months of training. Further studies should clarify to what extent an application in humans could be considered.
Osteoarthritis is the most common joint disease in Germany and one of the main causes of chronic pain. Wear and tear and chronic joint inflammation ensure that the cartilage in joints is broken down, so that eventually bone rubs against bone. Anti-inflammatory painkillers can relieve symptoms and slow but not reverse the breakdown. Previous therapeutic approaches try to replace the damaged cartilage with a healthy piece from another part of the body. However, the extraction point is injured in the process. Attempts to regrow the cartilage in the damaged joint have had the problem that the regrown cartilage was less stable than the natural one.
Nanoscaffold with electrical activity
A team led by Yang Lui from the University of Connecticut has now tested a new approach that also aims to regrow cartilage. While previous experiments usually used chemical growth factors, Luis’ team used electrical signals instead. “Studies have shown that cartilage responds to electrical stimulation,” the researchers explain. “Electrical fields promote tissue regeneration.” The researchers therefore constructed a scaffold made of nanofibers that generate an electrical voltage, so-called piezoelectricity, when subjected to mechanical stress. The material they used was poly-L-lactic acid, a biodegradable polymer that is used, among other things, to sew up surgical wounds.
In fact, with the newly developed scaffold, they succeeded in regrowing cartilage in a cell culture. To test its effectiveness in real joints, the researchers first inflicted severe cartilage damage in the knees of several rabbits, similar to that found in people affected by osteoarthritis. They then implanted the piezoelectric nanoframework in one group of rabbits, and a similar nanoframework without piezoelectric activity in another group. A group without an implant served as a control group.
Almost complete cartilage regeneration
After a four-week recovery period after surgery, the researchers put half of the rabbits in each group through an exercise program. The animals were given the opportunity to jump on a treadmill. The movement caused the piezoelectric material in the rabbits with the appropriate implant to be compressed and stretched, thus generating a weak electric field. After one to two months, the researchers killed the rabbits and examined the extent to which the cartilage had regenerated.
The result: in the animals that received a piezoelectric implant and then trained, the damaged cartilage had almost completely regenerated. It made no difference whether the training had lasted one month or two. “Even a month’s training led to significant cartilage healing and left little room for further improvement,” the researchers explain. In contrast, in rabbits that had not received a piezoelectric implant or had not been trained, the cartilage healing was significantly slower.
Further studies required
“Piezoelectricity is a phenomenon that also exists in the human body. Bone, cartilage, collagen, DNA and various proteins have a piezoelectric response. Our approach to healing cartilage is highly clinically transferable, and we will investigate the associated healing mechanisms,” says Liu. However, before the results can actually be translated into practice, further studies are required. “With our study, we have proven that the concept works in principle,” says Liu’s colleague Nguyen. “The result is fascinating, but we have yet to verify it in larger animals, which are closer in size and weight to humans. In addition, the animals should be observed in future studies for at least one year to ensure the durability of the cartilage.
Source: Yang Liu (University of Connecticut, USA) et al., Science Translational Medicine, doi: 10.1126/scitranslmed.abi7282