image: Heated by movement, nanostructures in the hydrogel matrix let go of the drugs it contains. view more
Credit: EPFL
Unlike our bones, the cartilage inside our joints is not vascularized (i.e., it has no blood vessels). This is one reason why cartilage does not heal well after an injury. In athletes in particular, joint injuries often result in cartilage degeneration and arthritis. The process is chronic and irreversible, and to this day, no effective treatment exists.
EPFL scientists Dominique Pioletti and Harm-Anton Klok have developed a hydrogel that promotes cartilage regeneration. In a joint, cartilage-producing cells only respond to treatment if they are mechanically stimulated at the same time, for example in the knee joint when a person is walking. To exploit this fact, the scientists created a hydrogel that delivers a therapeutic drug to the cells only when they are undergoing repetitive movement. The results of their work, which is part of the "Smart Materials" Swiss National Research Project (PNR 62), have been published in the journal Biomaterials.
Targeted and timed delivery
The cells that produce cartilage in a joint are called chondrocytes. When a joint is at rest, its chondrocytes are mostly inactive. However, when the same joint is moving, its chondrocytes activate receptors that are sensitive to growth factors produced by the body. At the same time, the chondrocytes become sensitive to treatments that help them regenerate damaged cartilage. "The receptors involved only appear after 5-20 minutes of repetitive movement," says Prof. Pioletti. "We therefore had to develop a way to time the release of the medication."
When a knee joint is in movement, friction generates heat. The method developed by the EPFL scientists is based on this concept. The viscous hydrogel matrix is designed to deliver the drugs it carries only when it reaches a certain threshold temperature, that is, after a specific number of repeated movements. Technically, the matrix contains liposomal nanoparticles as well as a therapeutic agent, TGF-beta growth factor. The matrix heats up during repeated movements. After 5-10 minutes, under the effect of the heat, the diameter of the nanoparticles decreases by a third, causing gaps to form in the matrix through which the growth factor can flow out into the target area. This mechanism thus makes it possible to time the release of the drug, delivering it at the most optimal moment to help the joint regenerate its cartilage.
A minimally invasive procedure
One way of implementing this approach in the future would involve arthroscopically implanting the matrix at the site of the damaged cartilage. Then, via targeted physical therapy, the joint would be mobilized to maximize the effect of the medicine.
More work has to be done before the team's innovative method actually reaches the market. At present, the team has proven the concept from a mechanical standpoint, having successfully delivered a colored dye used in place of the growth factor, but the technique still needs to be fine-tuned. "Several doctors have shown an interest in our approach," says Prof Pioletti, "and now we need to find partners and improve the method for in vivo tests."
Journal
Biomaterials