Two innovative new developments from the same lab have shown that deteriorated cartilage can be repaired and regrowth, first by using “dancing molecules” to target proteins needed for tissue regeneration, then with the help of a hybrid biomaterial that acts as a scaffold to encourage cartilage growth. They have the potential to do what nature cannot do on its own – regrow cartilage – which could be used to relieve all types of joint pain, including osteoarthritis, and also eliminate major surgeries such as total knee reconstructions.
“Cartilage is a critical component in our joints,” said lead researcher Samuel Stupp of Northwestern University. “When cartilage becomes damaged or breaks down over time, it can have a profound impact on people's overall health and mobility. The problem is that in adult humans, cartilage does not have the ability to naturally heal. Our new therapy can initiate repair in tissue that does not naturally regenerate. We think our treatment could help address a serious, unmet clinical need.”
The trial of a hybrid biomaterial to regrow damaged cartilage in sheep joints comes on the heels of work using synthetic nanofibers, or “dancing molecules,” that contain hundreds of thousands of molecules that provide powerful signals for cells. By changing their chemical structure to “dance,” or move rapidly, Stupp and his team found that these molecules can quickly find and interact with cellular receptors. Inside the body, the nanofibers align with the extracellular matrix of surrounding tissue, mimicking natural cellular communication.
“Cellular receptors are constantly on the move,” Stupp said. “By moving our molecules, 'dancing,' or even temporarily bouncing them off these structures, known as supramolecular polymers, they can more effectively engage with the receptors.”
The team developed a circular peptide to target the transforming growth factor beta-1 (TGFb-1) protein, which is found throughout the body and is important in cartilage (and bone) growth. When they compared the slow-moving molecules to the “dancing” structure, the researchers found that the latter was significantly more effective at activating TGFb-1 receptors.
Stupp Research Group/Northwestern University
“After three days, human cells exposed to longer assemblies of the more mobile molecules produced greater amounts of the protein components necessary for cartilage regeneration,” Stupp said. “For the production of collagen II, one of the components in the cartilage matrix, the dancing molecules, which include the cyclic peptide that activates the TGF-beta1 receptor, were even more effective than the native protein that performs this function in biological systems.”
The team is currently testing this system of dancing molecules on regenerating bone, with results to be published later this year. The team also hopes to take this development into clinical trial for spinal cord repair.
But that’s not the only discovery coming out of the Stupp lab; there’s another approach that’s seen cartilage regeneration in sheep joints. In the second study, instead of dancing molecules, the team developed a hybrid biomaterial made up of a bioactive peptide that binds to that all-important TGFb-1 protein and modified hyaluronic acid, the natural adhesive that lubricates the body’s components, including joints.
“Many people are familiar with hyaluronic acid because it’s a popular ingredient in skin care products,” Stupp said. “It also occurs naturally in many tissues in the human body, including the joints and brain. We chose it because it’s similar to the natural polymers found in cartilage.”
The team used this biomaterial to induce nanoscale fiber organization into bundles that mimic the natural structure of cartilage, essentially creating a bio-friendly scaffold that would encourage the body's cells to regenerate cartilage tissue on top of it.
This ‘rubbery adhesive’ biomaterial was implanted into the damaged knee cartilage of a sheep and within six months the tissue showed improved repair as well as new cartilage growth made up of natural biopolymers (collagen II and proteoglycans). This resulted in pain-free movement and effective stability in the previously damaged joint as the artificial scaffold naturally degraded while the new cartilage structure remained intact.
Samuel I. Stupp/Northwestern University
Samuel I. Stupp/Northwestern University
“A study done in a sheep model gives a better estimate of how the treatment will work in humans,” Stupp said. “In other smaller animals, cartilage regeneration occurs much more easily.”
The team believes this thick paste-like biomaterial could be used in surgery as a less invasive way to promote cartilage repair compared to current microfracture procedures.
“The main problem with the microfracture approach is that it often results in the formation of fibrocartilage, the cartilage in our ears, instead of the hyaline cartilage we need to have functional joints,” Stupp said. “By replacing the hyaline cartilage, our approach should be more resistant to wear and tear, solving the problem of poor mobility and joint pain in the long term while also eliminating the need for joint reconstruction with large pieces of hardware.”
The first study was published Journal of the American Chemical Societywhile the biomaterial study was published in the journal Proceedings of the National Academy of Sciences.
Source: Northwestern University [1], [2]