Researchers at Northwestern University have developed a novel bioactive material capable of regenerating high-quality cartilage in knee joints of large-animal models.

Though the material resembles a rubbery goo, it consists of a complex network of molecular components designed to replicate the natural environment of cartilage in the body.

In their recent study, published in Proceedings of the National Academy of Sciences, the researchers applied this material to damaged cartilage in the knee joints of animals. After six months, they observed significant cartilage repair, including the growth of new cartilage containing collagen II and proteoglycans, which are crucial for pain-free joint function.

With further development, this material could potentially be used to avoid knee replacement surgeries, treat degenerative diseases like osteoarthritis, and repair sports injuries such as ACL tears.

“Cartilage is a critical component in our joints,” said Samuel I. Stupp, who led the study at Northwestern. “When cartilage becomes damaged or breaks down over time, it can have a great impact on people’s overall health and mobility. The problem is that, in adult humans, cartilage does not have an inherent ability to heal. Our new therapy can induce repair in a tissue that does not naturally regenerate. We think our treatment could help address a serious, unmet clinical need.”

A pioneer of regenerative nanomedicine, Stupp holds multiple prestigious positions at Northwestern University and is the founding director of the Simpson Querrey Institute for BioNanotechnology. Jacob Lewis, a former Ph.D. student in Stupp’s lab, is the first author of the paper.

The new study builds on previous work from Stupp’s lab involving "dancing molecules" to activate human cartilage cells. The current research uses a hybrid biomaterial also developed in Stupp’s lab, composed of a bioactive peptide that binds to transforming growth factor beta-1 (TGFb-1) and modified hyaluronic acid.

“Many people are familiar with hyaluronic acid because it’s a popular ingredient in skincare products,” Stupp said. “It’s also naturally found in many tissues throughout the human body, including the joints and brain. We chose it because it resembles the natural polymers found in cartilage.”

Stupp’s team combined the bioactive peptide with chemically modified hyaluronic acid particles to create nanoscale fibers that mimic cartilage's natural structure. This scaffold encourages the body’s cells to regenerate cartilage tissue by using bioactive signals.

To test the material's effectiveness, researchers used sheep with cartilage defects in the stifle joint, a complex joint similar to the human knee, in Mark Markel's lab at the University of Wisconsin–Madison.

“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 readily.”

Researchers injected the paste-like material into cartilage defects, where it formed a rubbery matrix. New cartilage grew to fill the defect, and the quality of the repaired tissue was consistently higher than the control.

In the future, Stupp envisions the material being used during open-joint or arthroscopic surgeries. The current standard, microfracture surgery, often results in fibrocartilage, which is less durable than hyaline cartilage needed for functional joints.

“The main issue 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 the one we need to have functional joints,” Stupp said. “By regenerating hyaline cartilage, our approach should be more resistant to wear and tear, fixing the problem of poor mobility and joint pain for the long term while also avoiding the need for joint reconstruction with large pieces of hardware.”

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