Cartilage is a notoriously difficult tissue to repair, but now scientists at Northwestern University have developed a new bioactive material that has been able to effectively regenerate high-quality cartilage in the knee joints of sheep, whose knees bear similarities to those of humans. Although it looks like a slimy substance, the material is actually a complex network of molecular components, which work together to mimic the natural environment of cartilage in the body.
The researchers applied the material to damaged cartilage in the animals’ knee joints. Within just six months, they found improved repair, including the growth of new cartilage containing natural biopolymers (collagen II and proteoglycans), which allow painless mechanical resilience in the joints.
The scientists say that continued work with the new material could one day lead to it being used to prevent total knee replacement surgeries, treat degenerative diseases such as osteoarthritis, and repair sports-related injuries such as anterior cruciate ligament (ACL) tears. The results of the study have been published in the Proceedings of the National Academy of Sciences.
“Cartilage is a critical component in our joints,” said Northwestern’s Samuel I. Stupp, who led the study. “When cartilage is damaged or breaks down over time, it can have a major impact on a person’s overall health and mobility. The problem is that in adult humans, cartilage has no inherent ability to heal itself. Our new therapy can induce repair in tissue that does not naturally regenerate. We believe our treatment could help address a serious, unmet clinical need.”
A material that improves mobility and prevents long-term pain
A pioneer of regenerative nanomedicine, Stupp is the Board Professor of Materials Science and Engineering, Chemistry and Medicine, and Biomedical Engineering at Northwestern, where he is the founding director of the Simpson Querrey Institute for BioNanotechnology and its affiliated center, the Center for Regenerative Nanomedicine. The new study follows recently published work from Stupp’s lab, in which the team used “dancing molecules” to activate human cartilage cells to boost production of proteins that build the tissue matrix.
Instead of using dancing molecules, the new study evaluates a hybrid biomaterial also developed in Stupp’s lab. The new biomaterial consists of two components: a bioactive peptide that binds to transforming growth factor beta-1 (TGFb-1), a protein essential for cartilage growth and maintenance, and modified hyaluronic acid, a natural polysaccharide present in cartilage and the lubricating synovial fluid in joints.
“Many people are familiar with hyaluronic acid because it’s a popular ingredient in skin care products,” Stupp said. “It’s also found naturally in many tissues in the human body, including joints and the brain. We chose it because it resembles the natural polymers found in cartilage.”
Stupp’s team integrated the bioactive peptide and chemically modified hyaluronic acid particles to drive self-organization of nanoscale fibers into bundles that mimic the natural architecture of cartilage. The goal was to create an attractive scaffold for the body’s own cells to regenerate cartilage tissue. Using bioactive signals in the nanoscale fibers, the material encourages cartilage repair by the cells that populate the scaffold.
“Our new therapy can induce repair in tissue that does not regenerate naturally”
To evaluate the material’s effectiveness in promoting cartilage growth, the researchers tested it in sheep with cartilage defects in the stifle joint, a complex joint in the hind limbs similar to the human knee. This work was conducted in the lab of Mark Markel at the University of Wisconsin-Madison School of Veterinary Medicine.
According to Stupp, testing in a sheep model was vital. Like humans, sheep cartilage is stubborn and incredibly difficult to regenerate. Sheep knees and human knees also have similarities in weight-bearing, size and mechanical loads. “A study on a sheep model is more predictive of how the treatment will work in humans,” Stupp said. “In other, smaller animals, cartilage regeneration occurs much more easily.”
In the study, researchers injected the thick, paste-like material into cartilage defects, where it transformed into a rubbery matrix. Not only did new cartilage grow to fill the defect as the scaffold degraded, but the repaired tissue was consistently of higher quality compared to the control.
In the future, Stupp envisions the new material could be applied to joints during open or arthroscopic joint surgeries. The current standard of care is microfracture surgery, during which surgeons create tiny fractures in the underlying bone to induce new cartilage growth.
“The main problem with the microfracture approach is that it often results in the formation of fibrocartilage — the same cartilage in our ears — as opposed to hyaline cartilage, which is what we need for functional joints,” Stupp said. “By regenerating hyaline cartilage, our approach should be more resistant to wear and tear, solving the problem of poor mobility and long-term joint pain while avoiding the need for joint reconstruction with large pieces of hardware.”
